An interventional study of Homogeneous External-Beam Radiotherapy, 20 Gy in Five Fractions and Homogeneous External-Beam Radiotherapy, 25 Gy in Five Fractions in Solid Tumor, sponsored by Affidea Nu-med Center of Oncological DIagnostics and Therapy. Not yet recruiting at 1 site in Poland. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-11-02.
Sponsored by Affidea Nu-med Center of Oncological DIagnostics and Therapy · Not applicable, Interventional, and Treatment
This study will compare three ways of giving radiotherapy to relieve symptoms caused by a large solid tumor. Radiotherapy uses radiation to treat cancer. Researchers want to find out whether LATTICE radiotherapy, which gives a higher dose to small areas inside a tumor while treating the rest with a lower dose, improves symptom relief compared with two treatments that give a more even dose.
The study plans to enroll 426 adults. One tumor must be at least 7 centimeters across and have a volume of at least 100 cubic centimeters. It must cause a symptom rated at least 4 on a 0-to-10 severity scale. The symptom may be pain, pressure or fullness, difficulty breathing or swallowing, bleeding, or difficulty with an activity because of the tumor. All three study treatments must be technically suitable for the person.
Participants will be assigned by chance, with an equal chance of receiving one of three treatments:
Gray is a unit of radiation dose. The 66.7-gray dose is the total dose to the selected regions, not an additional 66.7 gray on top of 20 gray. Each treatment is given once a day on five consecutive working days. Participants and their treatment teams will know which treatment has been assigned.
Before assignment, each participant will choose the single tumor-related symptom they most want treatment to improve. The main assessment is about eight weeks after treatment. A response requires a decrease of at least 2 points in this symptom score, while the participant remains alive and has not needed unplanned local treatment of the study tumor through day 63 after the final session. Death or this additional local treatment counts as nonresponse, even if symptoms improved earlier. A missing symptom score in a participant who is alive and has not needed this treatment is handled separately in the analysis.
Researchers will also assess how quickly symptom relief starts, how long it lasts, quality of life, side effects, tumor changes on scans, further treatment, hospital use and survival. Medical care needed for comfort or safety will not be withheld. Some questionnaires can be completed by telephone if a participant cannot or does not wish to attend; telephone calls do not replace required examinations, blood tests or scans.
Hospital stays and days alive outside hospital are assessed during the first 90 days after assignment, including people who do not start or finish radiotherapy. Side effects are recorded before treatment and during follow-up; the acute treatment-related assessment extends to 90 days after the last radiotherapy session actually received. The first 15 participants assigned to LATTICE will receive additional treatment-plan and safety review within the randomized study. Participants will be followed for at least 12 months, where survival permits, with record-based or direct follow-up extending to 24 months when possible. A planned review of missing outcome information, without examining treatment effects, may increase enrollment to a maximum of 480 participants.
Purpose and study design
SCALE-LRT (Symptom-Control Assessment of LATTICE Escalation) is a prospective, multicenter, open-label, parallel-group, randomized phase IIb superiority trial in adults with symptomatic bulky solid tumors. It tests whether three-dimensional LATTICE spatially fractionated radiotherapy improves patient-reported symptom relief compared separately with homogeneous radiotherapy of 20 gray (Gy) in five fractions and 25 Gy in five fractions. LATTICE creates selected high-dose regions inside the tumor while maintaining a lower dose across the surrounding treatment volume.
The radiotherapy strategy is assigned through central randomization. One index lesion and one symptom attributable to that lesion are selected before randomization. The index lesion and exact symptom wording cannot change after allocation.
Participants are randomized in a 1:1:1 ratio. Allocation uses Pocock-Simon minimization with a random component, balancing participating center, pain versus non-pain target symptom, Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1 versus 2-3, and gross tumor volume (GTV) of 100 to less than 500 versus at least 500 cubic centimeters. Allocation is concealed until assignment. Participants and treating teams are not masked. Standardized symptom collection and allocation-masked imaging review are used where specified and feasible; the trial is not uniformly assessor-blinded.
Treatment strategies
Arm A receives homogeneous external-beam photon radiotherapy of 20 Gy in five 4-Gy fractions to the protocol-defined low-dose planning target volume, without an intentional intratumoral boost.
Arm B receives homogeneous external-beam photon radiotherapy of 25 Gy in five 5-Gy fractions to the same type of planning target volume, without an intentional intratumoral boost.
Arm C receives 20 Gy in five 4-Gy fractions to the low-dose planning target volume with a simultaneous integrated boost to a total of 66.7 Gy in five 13.34-Gy fractions in protocol-defined intratumoral high-dose regions. The boost is delivered during the same five fractions, not as an additional fraction or an additional 66.7 Gy. The high-dose regions use complete 1.5-centimeter spheres in a locked three-dimensional geometric pattern. At least three complete, protocol-conforming high-dose regions must be feasible. Individual high-dose regions may not be moved on the basis of positron emission tomography uptake or another biological imaging signal in the main randomized intervention.
All arms use intensity-modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT), protocol immobilization and motion management, and volumetric image-guided radiotherapy (IGRT) before each fraction. Hard organ-at-risk (OAR) constraints take precedence over target coverage. Eligibility requires documented clinical and technical feasibility of all three allocations before randomization; it does not require optimization of three complete treatment-ready plans. The assigned arm cannot be replaced because another regimen is operationally preferred.
Treatment is given once daily on five consecutive working days, ordinarily Monday to Friday. The first fraction should start within seven calendar days of randomization. Planned completion is within seven calendar days of the first fraction; completion within a maximum of ten calendar days is permitted only after a documented medical, public-holiday or technical interruption. Twice-daily or compensatory double fractions are prohibited. Protocol safety holds and replanning may be used when clinically required.
Primary symptom assessment
The participant chooses the symptom they most want treatment to improve after clinical attribution to the index lesion. Severity is measured on a numeric rating scale (NRS) from 0 to 10. Baseline severity must be at least 4. The symptom category, wording and recall period are fixed before allocation.
The primary endpoint is target-symptom response in the week-8 window, days 49-63 after the final fraction. Response requires a valid in-window NRS showing an improvement of at least 2 points from baseline, with the participant alive and free of index-lesion rescue through the fixed day-63 cutoff. Death or rescue on or before day 63 is nonresponse, regardless of an earlier improved score. Rescue means unplanned local treatment of the index lesion because of inadequate symptom control, progression, a complication or imminent risk. Escalation of supportive medicines alone is not rescue for the general target-symptom endpoint. A participant who is alive and rescue-free through day 63 but lacks a valid in-window score is missing for the primary estimand, rather than automatically a nonresponder.
If treatment is delayed, not initiated or not completed, the main patient-reported outcome schedule remains tied to the planned final-fraction date recorded at randomization. Actual treatment dates are retained and prespecified sensitivity analyses address the actual last fraction. Non-initiation, interruption or crossover does not remove a randomized participant from the intention-to-treat analysis.
Follow-up and complementary assessments
Symptoms, medicines and rescue treatment are recorded at baseline, the end of radiotherapy, day 7 and weeks 2, 4, 8 and 12. Complementary assessments include quality of life, physical function, patient global impression of change, patient-reported symptomatic adverse events (AEs), clinician-graded AEs, treatment completion, tumor response, clinically relevant local failure, overall survival, progression-free survival, healthcare use and days alive out of hospital. Protocol imaging is planned at week 12, with later imaging at months 6 and 12 when clinically appropriate and feasible. Follow-up continues for at least 12 months after randomization where survival permits, with record-based or direct follow-up to 24 months when possible.
Days alive and out of hospital are a nonconfirmatory secondary endpoint measured in all randomized participants as allocated over the fixed 90-calendar-day interval [randomization date, randomization date plus 90 days), namely days 0-89. Each day alive without an inpatient overnight contributes one day. All-cause planned and unplanned inpatient stays count; outpatient radiotherapy and same-day emergency care without admission are not inpatient stays. The day of death and subsequent days contribute zero. Dead and inpatient time are not subtracted twice; unknown status remains missing. Treatment delays, noninitiation, discontinuation, rescue and subsequent therapy do not reset this interval. Mortality and hospitalization components are reported separately. Detailed healthcare-utilization counts are exploratory, from randomization through this interval and, where available, month 12.
Consensus pain response using pain scores and oral morphine-equivalent dose is a nonconfirmatory secondary endpoint only in the subgroup whose target symptom was frozen as pain before randomization. The algorithm originates in bone-metastasis trials; its use for other sites is an adaptation. Custom volumetric-response categories are exploratory and mutually exclusive: complete disappearance (delta volume equals minus 100%); major reduction (minus 100% \< delta volume \<= minus 65%); moderate reduction (minus 65% \< delta volume \<= minus 30%); stable volume (minus 30% \< delta volume \< plus 30%); and increase (delta volume >= plus 30%). They do not replace RECIST or continuous volume-change analyses.
In-person assessments are preferred. Trained staff may collect protocol-authorized patient-reported, healthcare-use and survival information by telephone if a participant cannot or will not attend. Telephone contact does not substitute for physical examination, clinician-graded adverse-event assessment, laboratory testing or imaging.
Concomitant treatment and safety
Best supportive care is permitted in every arm and is not withheld to preserve an endpoint. Other necessary cancer treatments are managed under prespecified timing, interaction and documentation rules. Cytotoxic chemotherapy and antiangiogenic treatment must not overlap with protocol radiotherapy and ordinarily require at least a five-day interval before the first and after the final fraction, with longer intervals or documented prospective approval when applicable. Continuation of immunotherapy, endocrine treatment or targeted treatment requires participant-specific review. Unplanned rescue treatment is provided when clinically needed and is recorded.
Adverse events are collected from consent, with baseline and pre-radiotherapy events recorded separately. Acute events are new or worsened events with onset from the first actual fraction through 90 days after the actual final fraction; the intolerance/morbidity composite uses the same interval. Late events have onset after that cutoff. For permanent early discontinuation, the actual last fraction is used once course termination is confirmed. Actual dates, dose, fractions and observation duration are retained. Nonstarters remain in randomized SAE/death reporting and are labeled unexposed; all-treated and all-randomized safety summaries are distinct, and as-treated comparisons are not interpreted as pure randomized treatment effects. The planned final-fraction rule for patient-reported assessment scheduling remains unchanged.
The first 15 participants randomized to Arm C form an embedded safety and technical-implementation cohort. Cohort membership is fixed by randomization order, including nonstarters, and participants are not silently replaced by treated participants or completers. Plans receive prospective technical review. Safety days 30 and 90 are 30 and 90 days after the actual final fraction of the assigned course. For a documented definitive nonstarter, review maturity uses the planned final-fraction date recorded at randomization, with the participant explicitly labeled unexposed. All further randomization is paused when the fifteenth cohort participant reaches the defined safety day 30. Resumption requires mature day-30 safety data or an earlier clinically documented definitive outcome for all first 15 participants, plus documented Sponsor and Principal-Investigator authorization. A second review occurs when all 15 reach the defined safety day 90 or have an earlier definitive outcome. Loss to follow-up is not maturity or a definitive outcome. Additional Arm-C allocations before the pause do not replace this cohort; available additional exposure data are reviewed. Prespecified urgent triggers are unchanged, including at least 3 of the first 15 with qualifying treatment-related grade-3-or-higher nonhematologic events by their defined safety day 30. The Sponsor and Principal Investigator may expand the safety cohort if exposure is insufficient. Tumor lysis syndrome risk assessment and risk-adapted laboratory surveillance apply across all arms.
Planned sample and analysis
The initial target is 426 randomized participants, 142 per arm. A single blinded reassessment based only on pooled primary-outcome missingness may increase the total to a maximum of 480 without examining treatment effects. The primary analysis follows randomized assignment. The two confirmatory comparisons are Arm C versus Arm A and Arm C versus Arm B, with a two-sided Dunnett adjustment controlling family-wise type-I error at 0.05. Each comparison can support its own conclusion; superiority to both controls requires both adjusted comparisons to be positive. Arm B versus Arm A is a secondary, estimation-oriented comparison, not an equivalence test. Missing week-8 scores in participants alive and rescue-free are handled using multiple imputation, with prespecified sensitivity analyses. No formal comparative interim efficacy or futility analysis is planned.
Ancillary research
Biologically guided vertex placement and optional biomarker studies require a separately approved prospective substudy and appropriate consent.
Additional prespecified exploratory analyses and operational assessments
The following hypothesis-generating analyses and operational assessments are prespecified in the protocol. They do not replace the primary and secondary outcome measures or create additional confirmatory comparisons. Longitudinal symptom analyses include area-under-the-score-curve summaries at the registered symptom assessment times.
Dosimetry and clinical outcomes: Exploratory associations of spatial dose geometry, vertex number and vertex-to-gross-tumor-volume fraction, high-dose-target dose, dose-volume metrics, peak-to-valley dose ratio, conformity, dose gradient, dose spill, organ-at-risk proximity and delivered-dose reconstruction with symptom response, imaging cytoreduction and treatment-related morbidity. Each dosimetric exposure and clinical outcome is analyzed separately. Analyses are hypothesis-generating and do not infer a biological mechanism or a causal treatment effect from uncontrolled correlations. Planning and treatment dosimetry are related to clinical outcomes assessed through month 12.
Treatment-effect heterogeneity: Exploratory treatment-by-subgroup interaction analyses for maximum diameter (7 to less than 10, 10 to less than 15, or at least 15 cm), gross tumor volume (100 to less than 250, 250 to less than 500, or at least 500 cubic centimeters), anatomical site, histology/radiosensitivity class, pain versus non-pain target symptom, Eastern Cooperative Oncology Group performance status, baseline symptom score, previous nonoverlapping radiotherapy, systemic-treatment class/timing and treatment completion. Continuous size models supplement categories. Interaction estimates and confidence intervals are reported, rather than comparing significance within subgroups. These analyses may be underpowered. These analyses use the week-8 primary response and the separately specified time-to-event endpoints over their registered follow-up horizons.
Variation in treatment-related AEs and morbidity: Exploratory safety analyses according to anatomical site, gross tumor volume, organ-at-risk proximity or invasion, motion-management class, number of high-dose vertices, renal function and tumor-lysis-syndrome risk category. Outcomes include clinician-graded AEs and the separately registered morbidity composite; grades, attribution and event types remain separate. Analyses characterize safety variation and are not confirmatory efficacy tests. The assessment period extends from the first actual radiotherapy fraction through month 12; acute onset is from the first actual fraction through 90 days after the actual final fraction, with late onset thereafter.
Trial feasibility and outcome ascertainment: Pooled, arm-masked descriptive assessment of screening, recruitment, technical eligibility, time to treatment, completion, deviations, patient-reported outcome availability/timing, telephone use and reasons for missing data. Screening and randomized denominators are kept distinct. The first-year milestone uses the first 60 consecutive randomized participants without post-randomization selection and requires mature week-12 windows or earlier determinable outcomes. This assessment does not test comparative efficacy or report arm-specific primary response. An optional pooled, allocation-masked operational review may occur after approximately six months. An optional first-year feasibility analysis uses the first 60 consecutive randomized participants only after all have completed their week-12 windows or have an earlier documented event determining the relevant feasibility status. If fewer than 60 have mature follow-up at 12 months, a pooled descriptive recruitment update may be used internally; a clinical feasibility manuscript is not required. Comparative efficacy and arm-specific primary response are not examined or disclosed in these reviews.
Treatment delivery and site experience: Exploratory treatment-delivery summaries including treatment time, imaging/setup corrections, adaptive replanning, protocol deviations, patient-specific quality-assurance results and changes with site experience. Each technical metric is retained separately; this analysis does not create a combined technical-success score. Data cover planning through completion of radiotherapy, in treated participants.
Missing information and assessment mode: Exploratory analysis of missing patient-reported outcomes and in-person versus authorized telephone assessment. Reasons for missingness are coded, and exact assessment timing and mode are retained. Planned analyses include multiple imputation, inverse-probability weighting, pattern-mixture models and tipping-point sensitivity analyses. Known death or rescue failures remain distinct from an alive, rescue-free participant with a genuinely missing report. These analyses evaluate robustness and do not replace the primary responder estimand. These analyses concern information collected from baseline through week 12 after the final radiotherapy fraction, using the protocol-prespecified planned-date rule when treatment is delayed, not initiated or incomplete.
Conditional imaging research: Conditional ancillary analyses of baseline imaging heterogeneity, necrosis, spatial peak/valley response and early imaging change. Analyses are conducted only when acquisition and processing are prospectively harmonized in a separate locked ancillary plan. Imaging-derived features and their associations with clinical outcomes are hypothesis-generating; no biological mechanism is inferred from uncontrolled correlations. The protocol identifies baseline through month 12 as the potential observation period; specific measurements will require the separate prospective plan before the ancillary analyses can be implemented.
Conditional translational research: Conditional translational analyses of circulating biomarkers, immune signals or tissue. Samples and analyses are permitted only under separately approved consent and laboratory manuals. Biomarker findings and associations with clinical outcomes are exploratory, and no biological mechanism is inferred from uncontrolled correlations. Each biomarker is analyzed according to the prospectively approved ancillary plan rather than combined into an unprespecified score. The protocol identifies baseline through month 12 as the potential observation period; specific measurements will require the separately approved consent and laboratory manuals before this work can be implemented.
Affidea Nu-med Center of Oncological DIagnostics and Therapy is the lead sponsor of 7 studies on the registry; 7 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Brain metastases
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Homogeneous external-beam photon radiotherapy of 20 gray (Gy) in five 4-Gy fractions to the protocol-defined low-dose planning target volume, without an intentional intratumoral boost. One fraction is delivered daily on five consecutive working days, with protocol image guidance, normal-tissue constraints and quality assurance.
Radiation: Homogeneous External-Beam Radiotherapy, 20 Gy in Five Fractions
Homogeneous dose-escalated external-beam photon radiotherapy of 25 gray (Gy) in five 5-Gy fractions to the protocol-defined low-dose planning target volume, without an intentional intratumoral boost. The same five-session timing, image-guidance and safety framework applies.
Radiation: Homogeneous External-Beam Radiotherapy, 25 Gy in Five Fractions
External-beam photon LATTICE radiotherapy: 20 gray (Gy) in five 4-Gy fractions to the low-dose planning target volume with a simultaneous integrated boost to a total of 66.7 Gy in five 13.34-Gy fractions to protocol-defined intratumoral high-dose regions. The boost is delivered during the same five fractions. At least three complete 1.5-centimeter high-dose spheres must meet the locked geometry and hard normal-tissue constraints. The first 15 participants randomized to this arm form an embedded safety and technical cohort.
Radiation: LATTICE Radiotherapy, 20 Gy With a Simultaneous Integrated Boost to 66.7 Gy in Five Fractions
Homogeneous external-beam photon radiotherapy of 20 gray (Gy) in five 4-Gy fractions to the protocol-defined low-dose planning target volume, without an intentional intratumoral boost. One fraction is delivered daily on five consecutive working days, with protocol image guidance, normal-tissue constraints and quality assurance.
Homogeneous dose-escalated external-beam photon radiotherapy of 25 gray (Gy) in five 5-Gy fractions to the protocol-defined low-dose planning target volume, without an intentional intratumoral boost. The same five-session timing, image-guidance and safety framework applies.
External-beam photon LATTICE radiotherapy: 20 gray (Gy) in five 4-Gy fractions to the low-dose planning target volume with a simultaneous integrated boost to a total of 66.7 Gy in five 13.34-Gy fractions to protocol-defined intratumoral high-dose regions. The boost is delivered during the same five fractions. At least three complete 1.5-centimeter high-dose spheres must meet the locked geometry and hard normal-tissue constraints. The first 15 participants randomized to this arm form an embedded safety and technical cohort.
Percentage of Participants With Target-Symptom Response at Week 8
Participant-reported target-symptom numeric rating scale (NRS): 0 means no symptom and 10 means worst imaginable severity. The symptom and wording are frozen before randomization; baseline NRS is at least 4. Response requires an NRS reduction of at least 2 points within days 49-63 and being alive and free of protocol-defined index-lesion rescue through day 63 after the final fraction. Death or rescue on or before day 63 is nonresponse regardless of earlier improvement. If multiple valid scores occur, use the score closest to day 56; ties use the earlier score. Participants alive and rescue-free through day 63 without a valid in-window score have missing outcomes handled by multiple imputation, rather than automatic nonresponse. Events after day 63 do not alter classification. Analysis retains all randomized participants under assigned treatment.
Time frame: Baseline before randomization and days 49-63 after final fraction; fixed death/rescue cutoff day 63. For delayed, unstarted or incomplete treatment, use the planned final-fraction date.
Percentage of Participants With Target-Symptom Response at Weeks 4 and 12
At each landmark, response requires a participant-reported target-symptom numeric rating scale reduction of at least 2 points from the baseline score, using the same frozen symptom wording and 0-10 scale as the primary outcome. Participants must be alive and free of protocol-defined index-lesion rescue through the fixed end of the relevant window: day 35 for week 4 and day 98 for week 12. Death or rescue by that cutoff is nonresponse, irrespective of earlier improvement. Apply the primary nearest-target-date rule (target days 28 and 84; ties use the earlier value). An alive, rescue-free participant without a valid in-window score has a missing outcome. Proportions are reported separately at each landmark.
Time frame: Baseline and days 21-35 and 70-98 after final fraction, with death/rescue cutoffs at days 35 and 98. Planned final-fraction date applies if treatment is delayed, not started or incomplete.
Percentage of Participants With Durable Target-Symptom Response Through Week 12
Binary outcome requiring the participant to meet the protocol target-symptom response definition at both week 8 and week 12, with no protocol-defined index-lesion rescue. Each response requires a reduction of at least 2 points on the frozen 0-10 numeric rating scale from baseline and survival without rescue through the corresponding window-end cutoff. Death or rescue through day 98 precludes durable response. A valid score is required in each landmark window; missing scores are distinguished from known death/rescue failures. The outcome is reported in the randomized population, not only among week-8 responders.
Time frame: Week 8 (days 49-63) and week 12 (days 70-98) after final fraction; fixed final death/rescue cutoff day 98. Planned final-fraction date applies if treatment is delayed, not started or incomplete.
Change in Global Quality of Life on the Quality of Life Questionnaire Core 15 Palliative
Change from baseline in the global quality-of-life score of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 Palliative (EORTC QLQ-C15-PAL), a 15-item questionnaire for advanced cancer. Scoring follows the current manual and transforms scales to 0-100; higher global scores indicate better quality of life, so positive change indicates improvement. Week 8 is the main time point; weeks 4 and 12 are supportive. Analysis uses participants with evaluable patient-reported outcome measures, with a multiple-imputation sensitivity analysis. Reports must be the participant's own; telephone administration requires an authorized, validated mode.
Time frame: Baseline before randomization and weeks 4 (days 21-35), 8 (days 49-63) and 12 (days 70-98) after final fraction; week 8 is the main assessment.
Change in Physical Functioning on the Quality of Life Questionnaire Core 15 Palliative
Change from baseline in the physical-functioning score of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 Palliative (EORTC QLQ-C15-PAL). Scoring follows the current manual, with scales transformed to 0-100. Higher physical-functioning scores indicate better function, so positive change indicates improvement. Week 8 is the main time point; weeks 4 and 12 are supportive. Analysis uses participants with evaluable patient-reported outcome measures, with a multiple-imputation sensitivity analysis. The participant supplies the report; a caregiver cannot provide a proxy questionnaire.
Time frame: Baseline before randomization and weeks 4 (days 21-35), 8 (days 49-63) and 12 (days 70-98) after final fraction; week 8 is the main assessment.
Patient Global Impression of Change in the Target Symptom
Distribution across seven Patient Global Impression of Change categories and percentage reporting "much better" or "very much better". At each contact the participant rates change in the target symptom since treatment began: very much worse, much worse, minimally worse, no change, minimally better, much better, or very much better. The latter two categories define response. More favorable categories indicate greater benefit. Results are reported separately at weeks 4, 8 and 12. This measure supplements the target-symptom numeric rating scale and does not replace it.
Time frame: Weeks 4 (days 21-35), 8 (days 49-63) and 12 (days 70-98) after final fraction.
Participant-Reported Symptomatic Adverse Events
Prespecified core and site-specific attributes from the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). The core module covers pain, fatigue, decreased appetite, nausea, vomiting and shortness of breath. One site-specific module is selected from the locked operations manual before randomization and cannot change because of assigned treatment. Official current-language instruments are used; selected attributes are reported separately according to their official response scales rather than as an invented total score. Baseline values and trajectories through week 12 are analyzed in participants with evaluable patient reports.
Time frame: Baseline through week 12 after final fraction, including scheduled post-treatment contacts and weeks 4, 8 and 12.
Percentage of Participants With Clinically Significant Treatment Intolerance or Treatment-Related Morbidity
Composite occurrence of any: permanent discontinuation or omission of an assigned fraction because of an adverse event or clinical deterioration at least possibly related to radiotherapy; an adverse-event-related interruption preventing completion within 7 calendar days; a treatment-related serious adverse event or unplanned hospitalization; a treatment-related grade 3 or higher nonhematologic adverse event; clinical grade 3 or higher tumor lysis syndrome at least possibly related to radiotherapy; or treatment-related death. Events are graded using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 6.0. Each component, maximum grade, attribution, timing, resolution and organ-system category is reported separately. Safety summaries use both all-treated and all-randomized denominators.
Time frame: From the first actual radiotherapy fraction through 90 days after the actual final fraction of the assigned course.
Percentage of Participants Completing the Assigned Five-Fraction Course Without a Major Deviation
Completion of all five assigned radiotherapy fractions within 7 calendar days from fraction 1, or within the protocol-permitted maximum of 10 calendar days after a documented medical, public-holiday or technical interruption, without a protocol-defined major deviation. Participants are analyzed by randomized assignment; treatment non-initiation and incomplete courses are retained in the randomized denominator. Completion dates, interruptions and deviations are recorded.
Time frame: End of the assigned radiotherapy course: normally within 7 calendar days from fraction 1; maximum 10 calendar days after a documented permitted interruption.
Time to First Index-Lesion Rescue Treatment
Time from randomization to the first unplanned local intervention to the index lesion for inadequate symptom control, progression, a complication or imminent risk. Qualifying rescue includes re-irradiation, surgery, ablation, embolization, stenting, drainage, cementoplasty, stabilization or another invasive local procedure. Diagnostic biopsy alone and escalation of supportive medication alone are not rescue. Rescue dates, indication, urgency and procedure are recorded. Clinically indicated rescue is never delayed for outcome assessment.
Time frame: From randomization through month 12.
Overall Survival
Time from randomization to death from any cause. Participants alive are censored at the last known date alive. Survival is summarized at 3, 6, 12 and 24 months and by median survival where estimable. Vital status may be obtained at visits, by telephone, from treating clinicians, medical records or legally permitted registries; the source and date are recorded. Cause of death is not required for this outcome.
Time frame: From randomization to death or last known alive, assessed through 24 months.
Progression-Free Survival
Time from randomization to first documented progression according to Response Evaluation Criteria in Solid Tumors, version 1.1, at the index lesion or another site; unequivocal clinical progression recorded by the treating oncology team; or death from any cause. Starting new anticancer therapy without documented progression is not automatically an event and triggers record review and classification under the prespecified statistical analysis plan. Summaries are at 3, 6 and 12 months. Imaging frequency and reason are described. Sensitivities use interval censoring between last nonprogressive and first progressive assessments, scheduled-imaging windows, an imaging-progression-or-death definition and alternative censoring at new systemic therapy.
Time frame: From randomization through month 12; estimates at months 3, 6 and 12.
Cumulative Incidence of Clinically Relevant Index-Lesion Failure
First imaging or clinical progression of the index lesion leading to rescue treatment, unplanned hospitalization, major deterioration of target symptoms or death attributed primarily to local progression. Local imaging progression is assessed by Response Evaluation Criteria in Solid Tumors, version 1.1, where applicable. Attribution of death to the index lesion requires documented review by the Principal Investigator using available clinical evidence and without allocation information where feasible. Death without evidence that the index lesion was the principal cause is a competing event. Cumulative incidence is reported at 3, 6 and 12 months in the randomized population.
Time frame: From randomization through month 12; cumulative incidence at months 3, 6 and 12.
Percentage Change From Baseline in Index-Lesion Gross Tumor Volume
Percentage change in index-lesion gross tumor volume, calculated as 100 times the difference between follow-up and baseline volumes, divided by baseline volume. Negative values indicate reduction. Week 12 is the main assessment; months 6 and 12 are supportive where evaluable. The main scan-evaluable population consists of randomized participants alive with valid baseline and in-window follow-up imaging and no protocol-defined index-lesion rescue before that scan. Deaths, rescue and reasons for missing imaging are reported by arm. A treatment-policy sensitivity includes post-rescue images with rescue indicators; a worst-rank sensitivity ranks death and morphology-altering rescue unfavorably before observed changes. These survivor/scan-evaluable analyses are not intention-to-treat treatment effects.
Time frame: Baseline and week 12 (day 84 ±14), with supportive month 6 (day 182 ±30) and month 12 (day 365 ±45) assessments after final fraction.
Radiographic Response of the Index Lesion and Overall Measurable Disease
Index-lesion and overall measurable-disease response according to Response Evaluation Criteria in Solid Tumors, version 1.1, at week 12 and best response through month 12. Categories and objective response are reported where disease is measurable. The main population comprises randomized participants alive with valid baseline and follow-up imaging and no protocol-defined index-lesion rescue before the relevant scan. Rescue-related imaging non-evaluability and missingness are reported by arm. Post-rescue imaging is retained only in the treatment-policy sensitivity with an explicit rescue indicator; deaths and morphology-altering rescue are unfavorable in the prespecified worst-rank sensitivity. Scan-evaluable results are not interpreted as intention-to-treat treatment effects.
Time frame: Week 12 (day 84 ±14 after final fraction) and best response through month 12; month 6 and 12 imaging is obtained where clinically appropriate and evaluable.
Days Alive and Out of Hospital Through Day 90
Number of calendar days alive without an inpatient overnight during the fixed 90-day interval from randomization date (inclusive) to randomization date plus 90 days (exclusive; days 0-89). The range is 0-90; higher is better. All-cause planned and unplanned inpatient stays count. Outpatient radiotherapy and same-day emergency care without admission are not inpatient stays. The day of death and later days contribute zero; dead and inpatient time are not subtracted twice. Admission, discharge and death dates are retained. Unknown daily status is missing, not presumed out of hospital. All randomized participants are analyzed as allocated, including nonstarters. Delays, discontinuation, rescue and subsequent treatment do not reset the interval. Mortality and hospitalization components are reported separately.
Time frame: The fixed 90-calendar-day interval beginning on the date of randomization: days 0-89, with randomization date as day 0.
Acute Treatment-Related Adverse Events by Severity
Incidence of treatment-related adverse events (AEs), including separate percentages with grade 2 or higher and grade 3 or higher events, graded by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 6.0. Relationship is recorded as unrelated, unlikely, possibly, probably or definitely related to protocol radiotherapy. Events are tabulated by maximum grade, organ-system category, relationship, seriousness, timing and resolution. All serious AEs, grade-5 events and suspected tumor lysis syndrome are recorded and reported separately. Baseline abnormalities are recorded to distinguish new or worsening AEs. Safety summaries use all-treated and all-randomized denominators.
Time frame: From the first actual radiotherapy fraction through 90 days after the actual final fraction of the assigned course.
Late Treatment-Related Adverse Events and Morbidity
Incidence and maximum severity of late treatment-related adverse events or morbidity, including grade 2 or higher and grade 3 or higher events. Late events have onset more than 90 days after the actual final radiotherapy fraction and are graded by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 6.0. Site-specific events include ulceration or necrosis, bleeding, fistula or perforation, airway compromise, pneumonitis, myelopathy or neuropathy, fracture, edema or mass-effect flare, and tumor lysis syndrome. Attribution, seriousness, onset, resolution and interventions are recorded; all serious and grade-5 events are described separately. Related or serious events are followed until resolution, stabilization, death or loss to follow-up. Actual treatment dates, exposure and observation duration are retained, with all-treated and all-randomized summaries.
Time frame: Onset more than 90 days after the actual final radiotherapy fraction through month 12 or death; ongoing related or serious events are followed until resolution, stabilization, death or loss to follow-up.
International Consensus Pain Response in the Pain-Target Subgroup
International Consensus Pain Response Endpoint classification using treated-site pain and oral morphine-equivalent dose (OMED), in participants whose target symptom was frozen as pain before randomization. Complete response is pain score zero without increased OMED. Partial response is a reduction of at least 2 pain-score points without increased OMED, or an OMED reduction of at least 25% without increased pain. Pain progression and indeterminate categories follow the consensus algorithm. Conversion rules are fixed prospectively. Categories and response are reported separately at each landmark. This is a nonconfirmatory secondary endpoint. The algorithm originates from bone-metastasis trials; its application to other anatomical sites is an adaptation and is not claimed to be uniformly validated across all tumors.
Time frame: Weeks 4 (days 21-35), 8 (days 49-63) and 12 (days 70-98) after final fraction.
Longitudinal Target-Symptom Severity and Area Under the Score Curve
Repeated participant-reported target-symptom numeric rating scale scores and area under the longitudinal score curve. The same symptom, verbatim wording and recall period are frozen before randomization. The 11-point scale runs from 0, no symptom, to 10, worst imaginable severity; lower scores indicate lower symptom burden. Measurements are obtained at end of radiotherapy, day 7 and weeks 2, 4, 8 and 12. Analyses use longitudinal models and joint longitudinal-survival summaries, with missingness and assessment mode described; no caregiver proxy score is accepted.
Time frame: End of radiotherapy (day 0), day 7 (+/-1), day 14 (+/-3), day 28 (+/-7), day 56 (+/-7) and day 84 (+/-14), up to day 98. Day 0 is the final fraction, or the planned final-fraction date if treatment is delayed, not started or incomplete.
Time to First Clinically Meaningful Target-Symptom Improvement
Time from randomization to the first recorded reduction of at least 2 points from baseline on the frozen participant-reported target-symptom numeric rating scale. Scores range from 0, no symptom, to 10, worst imaginable severity; reduction indicates improvement. Assessments are retained with exact dates. This is an exploratory timing analysis rather than the fixed week-8 responder outcome, which has separate death/rescue rules.
Time frame: From randomization through the week-12 assessment (day 84 ±14 after final fraction).
Target-Symptom Response Using Alternative Prespecified Improvement Thresholds
Exploratory response proportions using reductions from baseline of at least 1, 2 or 3 points and at least 30% or 50% on the frozen participant-reported target-symptom numeric rating scale. The scale runs from 0, no symptom, to 10, worst imaginable severity. Each threshold is reported separately and is not combined into a new response score. Symptom-specific responder definitions are explored separately. These analyses do not replace the primary 2-point response definition or its fixed day-63 death/rescue rule.
Time frame: End of radiotherapy through week 12 after final fraction.
Quality-of-Life Scale Trajectories and Deterioration
Scale-specific longitudinal analyses of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 Palliative. The 15-item questionnaire covers global quality of life, physical and emotional functioning and key symptom scales. Each scale is scored separately according to the authorized manual and transformed to 0-100: higher functional/global scores are better, whereas higher symptom scores indicate greater burden. Exploratory analyses include trajectories, response using prespecified minimally important differences and time to deterioration. These analyses supplement the separately registered main global quality-of-life and physical-functioning change outcomes; no invented total score combines scales.
Time frame: Baseline through month 12 after final fraction.
Concordance Between Participant-Reported and Clinician-Graded Symptomatic Adverse Events
Exploratory comparison of participant-reported symptom attributes from the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events with clinician grading under the National Cancer Institute Common Terminology Criteria for Adverse Events, version 6.0. Core and frozen site-specific attributes are followed over time. Agreement and disagreement are assessed for corresponding symptoms and attributes; participant and clinician measures are retained separately and are not averaged into a composite score.
Time frame: Baseline through week 12 after final fraction.
Exploratory Volumetric Response Categories
Mutually exclusive exploratory categories based on percentage change in index-lesion gross tumor volume (delta V), calculated as 100 multiplied by (follow-up volume minus baseline volume), divided by baseline volume. Complete disappearance: delta V equals minus 100%. Major reduction without complete disappearance: minus 100% less than delta V and delta V at most minus 65%. Moderate reduction: minus 65% less than delta V and delta V at most minus 30%. Stable volume: minus 30% less than delta V and delta V less than plus 30%. Increase: delta V at least plus 30%. Thus exactly 30% reduction is a response, and exactly 30% increase is an increase. These custom exploratory categories are not validated response criteria and do not replace Response Evaluation Criteria in Solid Tumors, version 1.1. Frequencies are reported separately from continuous volume change in the prespecified scan-evaluable population.
Time frame: Week 12 (day 84 ±14), month 6 (day 182 ±30) and month 12 (day 365 ±45) after final fraction.
Spatial Patterns of Local Failure
Exploratory mapping of local failures to planned high-dose peaks, low-dose valleys, tumor periphery, necrotic regions and areas of undercoverage required by organ-at-risk constraints. Imaging-evaluable local failures are described according to their spatial relationship to the delivered/planned dose distribution. This is separate from the randomized-population cumulative incidence of clinically relevant local failure.
Time frame: Through month 12 after treatment.
Restricted Mean Overall Survival Through 6 and 12 Months
Restricted mean overall survival from randomization through the prespecified 6- and 12-month horizons. Overall survival ends at death from any cause; living participants are censored at the last known date alive. Restricted mean survival summarizes the area under the overall-survival curve up to each horizon and is reported separately from the median and landmark survival probabilities.
Time frame: From randomization through 6 months and through 12 months.
Restricted Mean Progression-Free Survival Through 6 and 12 Months
Restricted mean progression-free survival from randomization through the 6- and 12-month horizons. Events are first documented progression according to Response Evaluation Criteria in Solid Tumors, version 1.1, unequivocal clinical progression, or death. Starting new anticancer therapy without documented progression is not automatically an event. Restricted mean survival summarizes the area under the progression-free-survival curve up to each horizon, retaining the protocol's imaging-ascertainment and censoring sensitivity analyses.
Time frame: From randomization through 6 months and through 12 months.
Survival Conditional on Symptom or Imaging Assessment Landmarks
Exploratory conditional survival summaries among participants alive at each prespecified patient-reported symptom or imaging landmark. The protocol distinguishes these landmark populations from the full randomized cohort. Overall survival and progression-free survival retain their separately specified event definitions and are reported separately; conditioning is not interpreted as an intention-to-treat treatment effect.
Time frame: Prespecified symptom/imaging landmarks through month 12.
Healthcare Utilization and Acute-Care Contacts
Exploratory counts of hospital admissions and inpatient nights, emergency-department visits, unplanned outpatient acute-care contacts, invasive index-lesion procedures and re-irradiation. Each utilization type is reported separately with exact dates. Same-day emergency care without admission is separate from inpatient stays. Counts are collected from randomization during the fixed first 90-day interval and, where available, through month 12. Delayed, unstarted or discontinued treatment, rescue and subsequent therapy do not reset this clock. Days alive and out of hospital during the first 90 days after randomization remain a separate secondary endpoint.
Time frame: From randomization during the fixed 90-calendar-day interval [randomization date, randomization date plus 90 days), and, where available, through month 12.
Subsequent Systemic Anticancer Therapy and Local Procedures
Occurrence, type and dates of subsequent systemic therapy and index-lesion re-irradiation, surgery, ablation, embolization, drainage or other local procedures. Systemic therapy and each local intervention type are summarized separately. Protocol-defined index-lesion rescue remains separately recorded and is incorporated into the registered rescue and symptom outcomes when its criteria are met.
Time frame: From randomization through month 12.
Plan to share: No — No routine public release of individual participant data (IPD) or analysis code is planned. Any exceptional external access or secondary analysis requires prior written approval from the Sponsor and Principal Investigator, compatibility with participant consent and applicable ethics and data-protection requirements, a defined scientific purpose and minimum-necessary dataset, and an executed data-use or processing agreement. Aggregate registry results and peer-reviewed reports will be made public as required. No participant-level data repository, access timetable or commitment to provide IPD has been established.
Start is estimated for Dec 2026; primary completion for Mar 2030, 39 months later.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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