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RecruitingNCT051153311-2 PUNCHUpdated Sep 18, 2023

Palliative UNConventional Hypofractionation Trial for Metastatic Bone Disease

A Phase 3 interventional study of Experimental Radiation Dose and Conventional Radiation Dose in Metastatic Bone Tumor, sponsored by University of Cincinnati. Recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-09-18.

Sponsored by University of Cincinnati · Phase 3, Interventional, and Supportive care

Phase
Phase 3
Study type
Interventional
Enrollment
168
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

This is a randomized Phase III study evaluating the efficacy of hypofractionated and dose-escalated palliative radiation therapy in metastatic bone disease (MBD). Patients will be randomized 1:1 to the conventional (8 Gy in a single fraction) and experimental (16 Gy in 2 fractions) groups with baseline and subsequent assessment of both pain and quality of life metrics.

Read the detailed description

Metastatic Bone Disease (MBD) has been demonstrated to be a common clinical problem, and often presents with severe, if not debilitating pain. This often proceeds to affect a patient's emotional and even global functioning. Radiation therapy is an effective treatment commonly used in the palliation of these metastatic lesions, and improvements in QOL scores are associated with response to radiotherapy treatment. Although both 30 Gy/10 fractions and 8 Gy in a single fraction are considered standard of care in the palliative setting, single fraction treatment is associated with increased rates of local failure and retreatment. Considering that patients with MBD often have life-limiting disease, and frequently have great difficulty with undergoing extended radiotherapy treatments, there is a significant unmet need for palliative treatments that are effective, safe, timely, and provide a durable local tumor and pain control. The investigators hypothesize that utilizing a fractionation scheme with an escalated biologically equivalent dose will result in a higher proportion of patients responding to treatment, and will also lead to more durable responses.

02

Conditions studied

  • Metastatic Bone Tumor

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Keywords

  • Metastatic Bone Disease
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Patients must have histologically or cytologically confirmed history of solid cancer malignancy (including small cell lung cancer).
  2. Patients must have 1-3 new or newly painful metastatic lesions to bone as defined by CT scan, MRI, or PET scan. Lesions must be located in a long bone, pelvis/hip, spine, sacrum, or ribs. A lesion is "new" if it has occurred since any previous imaging, or if new cancer diagnosis, or new at presentation. A newly painful lesion is one that had been visible on previous imaging, but was either asymptomatic or minimally painful so that no treatment was pursued.
  3. There must be clearly attributable pain associated with the 1-3 new metastatic bone lesion(s) as documented on the Brief Pain Inventory and per investigator's determination that these imaging findings are consistent with the patient's described BPI pain from metastatic lesion(s).
  4. Age ≥18 years.
  5. ECOG performance status ≤3 or (Karnofsky ≥40%, see Appendix A).
  6. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial in the opinion of the investigator.
  7. Ability to understand and the willingness to sign written informed consent.

Exclusion criteria

Exclusion Criteria:

  1. Patients who have had or will have chemotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to commencing study RT. Patients undergoing treatment with hormonal or endocrine therapies will be eligible for this trial and may continue these through study radiotherapy.
  2. Patients with widespread metastatic disease, such that in the opinion of the PI would preclude an investigator from determining the origin of bone disease-related pain and/or response to palliative treatment.
  3. Patients who are receiving any other investigational agents. Patients who have received other investigational agents previously who are no longer receiving these investigational agents may be eligible at the discretion of the PI.
  4. Patients with complicated bone metastases, defined as having at least one or more of the following criteria:

    1. Nerve root compression
    2. Prior radiation to the spinal cord at that bone level
    3. Impending (score of 9 or more on Mirel's Criteria) or existing pathologic fracture
    4. Spinal cord compression
    5. cauda equina syndrome
  5. Patients who have been previously radiated to the primary anatomic site for which they are being considered for this trial, or have had surgical fixation of the site. However, patients may have undergone previous courses of radiotherapy to a primary site or separate site of metastatic disease if in the opinion of the investigator the patient will be able to tolerate palliative RT.
  6. Patients with uncontrolled intercurrent illness.
  7. Pregnant women are excluded from this study.
  8. Life expectancy of under 3 months in the opinion of the treating investigator.
  9. Liquid malignancies, including myeloma, lymphoma.
  10. Judgment by the investigator that the patient is unsuitable to participate in the study or the patient is unlikely to comply with study procedures, restrictions and requirements.
04

Study design

Phase
Phase 3
Primary purpose
Supportive care
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
168 participants (estimated)

Study arms

  • Active comparator
    Conventional Radiation Dose

    8 Gy in a single fraction

    Radiation: Conventional Radiation Dose

  • Experimental
    Experimental Radiation Dose

    16 Gy in 2 fractions

    Radiation: Experimental Radiation Dose

Interventions

  • RadiationExperimental Radiation Dose

    16 Gy in 2 fractions

  • RadiationConventional Radiation Dose

    8 Gy in a single fraction

05

What researchers measure

Primary outcomes

  1. Pain Response measured by the Brief Pain Inventory

    A primary objective evaluate the efficacy of the addition of a second 8 Gy fraction administered 1 week following the standard 8 Gy treatment currently utilized for palliation of symptomatic bone metastases in solid cancers, as measured by pain response at 1 month. The primary endpoint for this objective is pain response which will be determined using the Brief Pain Inventory (BPI) at one month.

    Time frame: 1 month post radiation completion.

  2. Pain Response measured by the Bone Mets Pain scale

    A primary objective evaluate the efficacy of the addition of a second 8 Gy fraction administered 1 week following the standard 8 Gy treatment currently utilized for palliation of symptomatic bone metastases in solid cancers, as measured by pain response at 1 month. The primary endpoint for this objective is pain response which will be classified using the International Consensus on Palliative Radiation for Future Trials on Bone Mets, which is a 4-point scale ranging from complete response to pain progression. Pain relief as measured by this scale and daily oral morphine equivalents (OME) will be graded at 1 month.

    Time frame: 1 month post radiation completion.

  3. Safety through 30 days post-radiation

    A second primary objective is to characterize the safety profile and adverse events (AE) of dose-escalated palliative radiotherapy. The primary endpoint for this objective is Adverse events will be described and coded based upon the NCI CTCAE v5.0 through 30 days after end of a subject's treatment.

    Time frame: 30 days post radiation completion.

Secondary outcomes

  1. Time to pain relief

    A secondary objective is to determine time to maximal pain relief, and to determine pain response at 2, 3, and 6 months. Pain response at 2, 3, and 6 months will be assessed using the Brief Pain Inventory (BPI), and classified using the International Consensus on Palliative Radiation for Future Trials on Bone Mets; as well as daily oral morphine equivalents (OME). Time to maximal pain relief will be determined from BPI questionnaires and International Consensus on Palliative Radiation for Future Trials on Bone Mets scale data.

    Time frame: 2, 3, and 6 months after completion of radiation treatment.

  2. Quality of Life (EORTC QLQ-C30) at Baseline, 1, 3, and 6 months post treatment

    Another secondary objective is to evaluate the impact of standard and dose-escalated arms of palliative radiotherapy on quality of life. Quality of life data will be obtained via European Organisation for Research and Treatment of Cancer Quality of Life Cancer Patients (EORTC QLQ-C30 (version 3)) at baseline and 1-, 3-, and 6-months post-treatment.

    Time frame: Baseline, 1, 3, and 6 months post radiation treatment.

  3. Quality of Life (EORTC QLQBM22) at Baseline, 1, 3, and 6 months post treatment

    Another secondary objective is to evaluate the impact of standard and dose-escalated arms of palliative radiotherapy on quality of life. Quality of life data will be obtained via European Organisation for Research and Treatment of Cancer Quality of Life Bone Metastases (EORTC QLQBM22) at baseline and 1-, 3-, and 6-months post-treatment.

    Time frame: Baseline, 1, 3, and 6 months post radiation treatment.

  4. Overall survival through 2 years post-treatment.

    Another secondary objective is to determine differences in overall survival between subjects receiving standard and dose-escalated palliative radiotherapy. Overall survival (OS) data from the date of completion of radiation therapy will be obtained from departmental records and electronic medical records through 2 years post end of radiation treatment.

    Time frame: 2 years post treatment.

  5. Retreatment rates through 2 years post-treatment.

    Another secondary objective is to determine differences in retreatment rates between subjects receiving standard and dose-escalated palliative radiotherapy. Retreatment rates data from the date of completion of radiation therapy will be obtained from departmental records and electronic medical records through 2 years post end of radiation treatment.

    Time frame: 2 years post treatment.

06

Study locations

1 of 1 sites recruiting
  • University of Cincinnati
    Cincinnati, Ohio 45267, United States
    • Christine Vollmer · Contact · mccordce@ucmail.uc.edu · 513-213-3203
    • Timothy Struve, MD · Principal investigator
    Recruiting
07

Registry details

Key details

Study ID
NCT05115331
Lead sponsor
University of Cincinnati
Responsible party
Timothy Struve (Assistant Professor, University of Cincinnati) — Principal investigator
First posted
Nov 10, 2021
Start date
Nov 24, 2021
Primary completion
Nov 24, 2024 (estimated)
Completion
Nov 24, 2025 (estimated)
Last update
Sep 18, 2023

Study contacts

UCCC Clinical Trials Office
Contact
Cancer@UCHealth.com
513-584-7698
Christine Vollmer
Contact
mccordce@ucmail.uc.edu
513-213-3203
Timothy Struve, MD
principal investigator · University of Cincinnati

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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