A Phase 2 interventional study of Alectinib and Vismodegib in Cancer of Unknown Primary Site, sponsored by Hoffmann-La Roche. Completed at 125 sites in 33 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-11-19.
Sponsored by Hoffmann-La Roche · Phase 2, Interventional, and Treatment
This study will compare the efficacy and safety of molecularly-guided therapy versus standard platinum-containing chemotherapy in participants with poor-prognosis cancer of unknown primary site (CUP; non-specific subset) who have achieved disease control after 3 cycles of first-line platinum based induction chemotherapy.
101 studies on the registry are indexed under Neoplasms, Unknown Primary; 19 are open to participants now.
This study's enrollment of 529 is above the median of 52 across 63 interventional studies indexed under Neoplasms, Unknown Primary.
Browse Neoplasms, Unknown Primary studies →Hoffmann-La Roche is the lead sponsor of 2,101 studies on the registry; 87 are open to participants now.
Of its 330 completed or terminated interventional studies of FDA-regulated products, 248 (75%) have results posted.
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.
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
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 amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
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.
Line of therapy
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
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.
Measurable disease
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
RECIST
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
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.
Leptomeningeal disease
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants will be assigned to molecularly-guided therapy based on genomic profile.
Drug: Alectinib · Drug: Vismodegib · Drug: Ipatasertib · Drug: Olaparib · Drug: Erlotinib · Drug: Bevacizumab · Drug: Vemurafenib · Drug: Cobimetinib · Drug: Trastuzumab Subcutaneous (SC) · Drug: Pertuzumab · Drug: Atezolizumab · Drug: Paclitaxel · Drug: Entrectinib · Drug: Ivosidenib · Drug: Pemigatinib
Participants will receive platinum-based chemotherapy (Carboplatin or Cisplatin in combination with Gemcitabine or Paclitaxel).
Drug: Trastuzumab Subcutaneous (SC) · Drug: Pertuzumab · Drug: Carboplatin · Drug: Paclitaxel · Drug: Cisplatin · Drug: Gemcitabine
Alectinib will be administered orally at the label-recommended dose (600 mg) twice daily until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months).
Vismodegib will be administered orally at the label-recommended dose (150 mg) once daily until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months).
Ipatasertib will be administered orally at the label-recommended dose (400 mg) once daily on Days 1-21 of each 28-day Cycle in combination with paclitaxel, and as monotherapy after the final administration of paclitaxel, until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months).
Olaparib will be administered orally at the label-recommended dose (400 mg) twice daily until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months).
Erlotinib will be administered orally in combination with Bevacizumab at the label recommended dose (150 mg) once daily until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months)
Bevacizumab will be administered intravenously at 15mg/kg every 3 weeks in combination with Erlotinib until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months)
Vemurafenib will be administered orally, 960 mg twice daily, in combination with Cobimetinib, until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months)
Cobimetinib will be administered orally, 60mg once daily, in combination with Vemurafenib, on Days 1-21 of each 28-day Cycle, until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months)
Trastuzumab will be administered subcutaneously, 600 mg every 3 weeks, in combination with Pertuzumab and chemotherapy, until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months)
Pertuzumab will be initially be administered intravenously, 840 mg, followed by 420 mg every 3 weeks, in combination with Trastuzumab and chemotherapy, until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months)
Atezolizumab will be administered intravenously at the label-recommended dose (1200 mg), alone or in combination with chemotherapy, every 3 weeks until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months).
Carboplatin will be administered intravenously at the area under the curve (AUC) dose once every 3 weeks for up to 9 Cycles (Cycle = 21 days) in some combination with the following: Paclitaxel, Gemcitabine, Atezolizumab, Pertuzumab, and Trastuzumab SC.
Paclitaxel will be administered intravenously, 175 mg/m\^2, once every 3 weeks for up to 9 cycles (Cycle = 21 days) in some combination with the following: Carboplatin, Ipatasertib, Atezolizumab, Pertuzumab, and Trastuzumab SC
Cisplatin will be administered intravenously, 60-75 mg/m\^2, once every three weeks, for up to 9 cycles (Cycle = 21 days) in some combination with the following: Gemcitabine, Paclitaxel, Atezolizumab, Pertuzumab, and Trastuzumab SC.
Gemcitabine will be administered intravenously, 1000 mg/m\^2, twice every three weeks for up to 9 cycles (Cycle = 21 days) in some combination with the following: Cisplatin, Carboplatin, Atezolizumab, Pertuzumab, and Trastuzumab SC.
Entrectinib will be administered orally at the label-recommended dose (600 mg) once daily until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months).
Ivosidenib will be administered orally at the label-recommended dose (500mg) once daily across a 28-day treatment cycle until loss of clinical benefit or unacceptable toxicity.
Pemigatinib will be administered orally at the label-recommended dose (13.5mg) once daily across a 21-day treatment cycle until loss of clinical benefit or unacceptable toxicity.
Progression Free Survival (PFS) as Assessed by the Investigator According to Response Evaluation Criteria In Solid Tumors v1.1 (RECIST v1.1)
This efficacy objective was to evaluate the efficacy of MGT vs platinum chemotherapy in term of PFS in participants with CUP whose best response to 3 cycles of platinum induction chemotherapy was assessed CR, PR, or SD.
Time frame: From randomization to the first occurrence of disease progression or death from any cause, until 330 PFS events were observed (approx. 4.3 years for MGT Cat 1 and 3.4 years for Chemotherapy Cat 1).
Overall Survival (OS)
Time frame: From randomization to death from any cause (approx. 4 years)
Objective Response Rate (ORR)
Time frame: Two consecutive occurrences of complete or partial response >/=4 weeks apart (up to approximately 4 months)
Duration of Response (DOR)
Time frame: From the first documentation of a complete response (CR) or partial response (PR) to disease progression or death from any cause, whichever occurs first (up to approximately 4 years)
Disease Control Rate (DCR)
Time frame: From randomization to death from any cause, through the end of study (approximately 4 years)
| Milestone | Molecularly-Guided Therapy (MGT) Category 1 | Chemotherapy Category 1 | Category 2 |
|---|---|---|---|
| Started | 326 | 110 | 93 |
| Completed | 0 | 0 | 0 |
| Not completed | 326 | 110 | 93 |
| Withdrew: Death | 227 | 79 | 84 |
| Withdrew: Exclusion criteria | 1 | 0 | 0 |
| Withdrew: Lost to follow-up | 4 | 3 | 3 |
| Withdrew: No profile due to technical failure | 1 | 0 | 0 |
| Withdrew: Physician decision | 3 | 1 | 0 |
| Withdrew: Withdrawal by subject | 11 | 6 | 2 |
| Withdrew: Study terminated by sponsor | 79 | 21 | 4 |
This efficacy objective was to evaluate the efficacy of MGT vs platinum chemotherapy in term of PFS in participants with CUP whose best response to 3 cycles of platinum induction chemotherapy was assessed CR, PR, or SD.
| Months | Molecularly-Guided Therapy (MGT) Category 1 | Chemotherapy Category 1 |
|---|---|---|
| Progression Free Survival (PFS) as Assessed by the Investigator According to Response Evaluation Criteria In Solid Tumors v1.1 (RECIST v1.1) | 6.14 (4.70 to 6.47) | 4.40 (4.17 to 6.37) |
| Months | Molecularly-Guided Therapy MGT) Category 1 | Chemotherapy Category 1 |
|---|---|---|
| Overall Survival (OS) | 15.18 (13.90 to 18.43) | 12.78 (9.86 to 15.38) |
| Percentage of participants | Molecularly-Guided Therapy MGT) Category 1 | Chemotherapy Category 1 |
|---|---|---|
| Complete response (CR) | 4.9 (2.83 to 7.85) | 3.6 (1.00 to 9.05) |
| Partial response (PR) | 12.9 (9.45 to 17.01) | 4.5 (1.49 to 10.29) |
| Stable disease (SD) | 44.5 (39.00 to 50.06) | 49.1 (39.43 to 58.80) |
| Non-CR/Non-PD | 7.1 (4.52 to 10.40) | 6.4 (2.60 to 12.67) |
| Not Applicable (NA) | 2.5 (1.07 to 4.78) | 2.7 (0.57 to 7.76) |
| Progressive disease (PD) | 17.8 (13.80 to 22.38) | 21.8 (14.51 to 30.70) |
| Not evaluable participants | 0.6 (0.07 to 2.20) | 0 (0.00 to 3.30) |
| Missing participants | 9.8 (6.81 to 13.57) | 11.8 (6.45 to 19.36) |
| Months | Molecularly-Guided Therapy MGT) Category 1 | Chemotherapy Category 1 |
|---|---|---|
| Duration of Response (DOR) | 16.39 (8.08 to NA) | NA (4.14 to NA) |
| Percentage of responders | Molecularly-Guided Therapy MGT) Category 1 | Chemotherapy Category 1 |
|---|---|---|
| Disease Control Rate (DCR) | 64.7 (59.27 to 69.91) | 60.0 (50.22 to 69.22) |
Collected over Approximately 4.5 years. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Molecularly-Guided Therapy (MGT) Category 1 | 227/326 (69.6%) | 119/312 (38.1%) | 279/312 (89.4%) |
| Chemotherapy Category 1 | 79/110 (71.8%) | 15/102 (14.7%) | 81/102 (79.4%) |
| Category 2 | 84/93 (90.3%) | 39/93 (41.9%) | 73/93 (78.5%) |
| Event | Molecularly-Guided Therapy (MGT) Category 1 | Chemotherapy Category 1 | Category 2 |
|---|---|---|---|
| AnaemiaBlood and lymphatic system disorders | 4/312 | 0/102 | 5/93 |
| SepsisInfections and infestations | 3/312 | 0/102 | 4/93 |
| Atrial fibrillationCardiac disorders | 0/312 | 0/102 | 3/93 |
| PyrexiaGeneral disorders | 7/312 | 0/102 | 2/93 |
| COVID-19Infections and infestations | 7/312 | 1/102 | 2/93 |
| Urinary tract infectionInfections and infestations | 6/312 | 0/102 | 2/93 |
| UrosepsisInfections and infestations | 0/312 | 1/102 | 2/93 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 1/312 | 0/102 | 2/93 |
| Ischaemic strokeNervous system disorders | 1/312 | 0/102 | 2/93 |
| Renal failureRenal and urinary disorders | 0/312 | 0/102 | 2/93 |
| Event | Molecularly-Guided Therapy (MGT) Category 1 | Chemotherapy Category 1 | Category 2 |
|---|---|---|---|
| AnaemiaBlood and lymphatic system disorders | 111/312 | 30/102 | 37/93 |
| NauseaGastrointestinal disorders | 88/312 | 20/102 | 23/93 |
| DiarrhoeaGastrointestinal disorders | 76/312 | 6/102 | 9/93 |
| FatigueGeneral disorders | 69/312 | 14/102 | 22/93 |
| NeutropeniaBlood and lymphatic system disorders | 62/312 | 24/102 | 11/93 |
| AstheniaGeneral disorders | 60/312 | 15/102 | 15/93 |
| Decreased appetiteMetabolism and nutrition disorders | 60/312 | 10/102 | 14/93 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 52/312 | 6/102 | 6/93 |
| ThrombocytopeniaBlood and lymphatic system disorders | 49/312 | 14/102 | 13/93 |
| ConstipationGastrointestinal disorders | 43/312 | 12/102 | 14/93 |
| Age, Continuous(Years) | Molecularly-Guided Therapy (MGT) Category 1 | Chemotherapy Category 1 | Category 2 | Total |
|---|---|---|---|---|
| Mean | 60.5 ± 11.5 | 61.1 ± 11.3 | 59.2 ± 12.7 | 60.42 ± 11.62 |
| Sex: Female, Male(Participants) | Molecularly-Guided Therapy (MGT) Category 1 | Chemotherapy Category 1 | Category 2 | Total |
|---|---|---|---|---|
| Female | 161 | 53 | 44 | 258 |
| Male | 165 | 57 | 49 | 271 |
| Race/Ethnicity, Customized(Participants) | Molecularly-Guided Therapy (MGT) Category 1 | Chemotherapy Category 1 | Category 2 | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 4 | 3 | 1 | 8 |
| Asian | 31 | 12 | 7 | 50 |
| Black or African American | 5 | 0 | 0 | 5 |
| Unknown | 43 | 14 | 15 | 72 |
| White | 242 | 81 | 70 | 393 |
| Missing | 1 | 0 | 0 | 1 |
| Race/Ethnicity, Customized(Participants) | Molecularly-Guided Therapy (MGT) Category 1 | Chemotherapy Category 1 | Category 2 | Total |
|---|---|---|---|---|
| Hispanic or Latino | 22 | 9 | 4 | 35 |
| Not Hispanic or Latino | 252 | 85 | 76 | 413 |
| Not Stated | 31 | 11 | 7 | 49 |
| Unknown | 21 | 5 | 6 | 32 |
Showing the first 100 of 125 sites across 33 countries. Choose a country and city above to see the rest.
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing
Ran from Jul 2018 to primary completion in Feb 2023, 55 months.
Results were first posted in Jun 2024, 1 year 4 months after primary completion.
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This study is completed, as verified in Nov 2025. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Olaparib · Pertuzumab · Atezolizumab · Ivosidenib · Pemigatinib