NCT03498521

A Phase II Randomized Study Comparing the Efficacy and Safety of Targeted Therapy or Cancer Immunotherapy Versus Platinum-Based Chemotherapy in Patients With Cancer of Unknown Primary Site

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

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 529 (actual)
• Sponsor: Hoffmann-La Roche · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Conditions

• Cancer of Unknown Primary Site

Interventions

Type	Name	Description
DRUG	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).
DRUG	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).
DRUG	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).
DRUG	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).
DRUG	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)
DRUG	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)
DRUG	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)
DRUG	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)
DRUG	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)
DRUG	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)
DRUG	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).
DRUG	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.
DRUG	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
DRUG	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.
DRUG	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.
DRUG	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).
DRUG	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.
DRUG	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.

Timeline

• Start date: 2018-07-10
• Primary completion: 2023-02-14
• Completion: 2024-11-07
• First posted: 2018-04-13
• Last updated: 2025-11-19
• Results posted: 2024-06-14

Locations

125 sites across 33 countries: Australia, Austria, Brazil, Bulgaria, Chile, Colombia, Croatia, Czechia, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Japan, Latvia, Mexico, Netherlands, Norway, Peru, Poland, Portugal, Romania, South Korea, Spain, Switzerland, Thailand, Turkey (Türkiye), United Kingdom

Regulatory

• FDA-regulated drug study