Clinical trial

A Phase II, Randomized, Active-Controlled, Multi-Center Study Comparing the Efficacy and Safety of Targeted Therapy or Cancer Immunotherapy Guided by Genomic Profiling Versus Platinum-Based Chemotherapy in Patients With Cancer of Unknown Primary Site Who Have Received Three Cycles of Platinum Doublet Chemotherapy

Name

MX39795

Description

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.

Trial arms

Trial start

2018-07-10

Estimated PCD

2023-02-14

Trial end

2024-06-09

Status

Active (not recruiting)

Phase

Early phase I

Treatment

Alectinib

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).

Arms:

Molecularly-Guided Therapy

Vismodegib

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).

Arms:

Molecularly-Guided Therapy

Ipatasertib

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).

Arms:

Molecularly-Guided Therapy

Olaparib

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).

Arms:

Molecularly-Guided Therapy

Erlotinib

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)

Arms:

Molecularly-Guided Therapy

Bevacizumab

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)

Arms:

Molecularly-Guided Therapy

Vemurafenib

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)

Arms:

Molecularly-Guided Therapy

Cobimetinib

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)

Arms:

Molecularly-Guided Therapy

Trastuzumab Subcutaneous (SC)

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)

Arms:

Molecularly-Guided Therapy, Platinum-Based Chemotherapy

Pertuzumab

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)

Arms:

Molecularly-Guided Therapy, Platinum-Based Chemotherapy

Atezolizumab

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).

Arms:

Molecularly-Guided Therapy

Carboplatin

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.

Arms:

Platinum-Based Chemotherapy

Paclitaxel

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

Arms:

Molecularly-Guided Therapy, Platinum-Based Chemotherapy

Cisplatin

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.

Arms:

Platinum-Based Chemotherapy

Gemcitabine

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.

Arms:

Platinum-Based Chemotherapy

Entrectinib

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).

Arms:

Molecularly-Guided Therapy

Ivosidenib

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.

Arms:

Molecularly-Guided Therapy

Pemigatinib

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.

Arms:

Molecularly-Guided Therapy

Size

790

Primary endpoint

Progression Free Survival (PFS1)

From randomization to the first occurrence of disease progression as assessed by the investigator according to Response Evaluation Criteria In Solid Tumors v1.1 (RECIST v1.1) or death from any cause, through the end of study (approximately 70 months)

Eligibility criteria

Inclusion Criteria: * Histologically-confirmed unresectable cancer of unknown primary site (CUP) diagnosed according to criteria defined in the 2015 European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for CUP * No prior lines of systemic therapy for the treatment of CUP * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Candidate for platinum-based chemotherapy (according to the reference information for the intended chemotherapy) * At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) * Formalin-Fixed Paraffin-Embedded (FFPE) tumor tissue sample \</= 4 months old that is expected to be sufficient for generation of a comprehensive genomic profile at a central reference pathology laboratory Exclusion Criteria: * Squamous cell CUP * Participants who can be assigned to a specific subset of CUP for which a specific treatment is recommended by the 2015 ESMO Clinical Practice Guidelines for CUP or with a clinical and IHC profile indicative of a specific primary tumor (favorable prognosis CUP subsets): Poorly differentiated carcinoma with midline distribution; women with papillary adenocarcinoma of the peritoneal cavity; women with adenocarcinoma involving only the axillary lymph nodes; squamous cell carcinoma of the cervical lymph nodes; poorly differentiated neuroendocrine tumors; men with blastic bone metastases and elevated prostate-specific antigen (PSA); participants with a single, small, potentially resectable tumor; colon cancer-type CUP, including participants with a CK7 negative, CK20 positive, CDX-2 positive immunohistochemistry profile; CK7-positive, CK20-negative and TTF-1 positive tumors in a context suggestive of lung adenocarcinoma or thyroid cancer; IHC profile definitely indicative of breast cancer OR an IHC profile indicative of breast cancer and either a history of breast cancer or lymph nodes in the drainage areas of the breast; high-grade serious carcinoma histology and elevated CA125 tumor marker and/or a mass in the gynecological tract or any tumor mass or lymph node in the abdominal cavity; IHC profile suggestive of renal cell carcinoma and renal lesions, with a Bosniak classification higher than IIF; IHC profile compatible with cholangiocarcinoma or pancreatobiliary (or upper gastrointestinal carcinoma) AND 1 or 2 liver lesions without extrahepatic disease or with only pulmonary metastases and/or lymph nodes in the drainage areas of the liver * Known presence of brain or spinal cord metastasis (including metastases that have been irradiated only) * Histology and immunohistology profiles (per 2015 ESMO guidelines) that are not adenocarcinoma or poorly differentiated carcinoma/adenocarcinoma * History or known presence of leptomeningeal disease * Known human immunodeficiency virus (HIV) infection * Significant cardiovascular disease * Prior allogeneic stem cell or solid organ transplantation * Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or for up to 7 months after the final dose of treatment

Protocol

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Updated at

2023-11-18

1 organization

17 products

1 drug

1 indication

Organization

Hoffmann La Roche

Product

Vismodegib

Indication

Cancer of Unknown Primary Site