A Study Comparing the Efficacy and Safety of Targeted Therapy or Cancer Immunotherapy Guided by molecular profiling Versus Platinum-Based Chemotherapy in Patients with Cancer of Unknown Primary Site who Have Received Three Cycles of Platinum Doublet Chemotherapy

Phase 1

Conditions: Cancer of Unknown Primary Site
MedDRA version: 20.0Level: LLTClassification code 10032248Term: Other malignant neoplasm of unspecified siteSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2017-003040-20-FR

Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 790

Inclusion Criteria

• Age >=18 years
• Histologically-confirmed metastatic or advanced unresectable CUP
• At least one lesion that is measurable according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
• Availability of a tumor Formalin-fixed paraffin-embedded(FFPE) block <=3 months old at Screening that is sufficient for generation of a Foundation One® comprehensive genomic profile at a central reference pathology laboratory
• Availability of test reports confirming local CUP diagnosis If test reports confirming local CUP diagnosis are not available, an FFPE block must be submitted that is sufficient to allow for central confirmation of CUP diagnosis
• Each patient must provide a blood sample for Foundation ACT® genomic profiling, which will be used to assign molecularly-guided therapy ONLY in those patients for whom a Foundation One® report could not be generated
• No prior systemic therapy for the treatment of CUP
• ECOG performance status of 0 or 1
• Life expectancy >=12 weeks
• Eligible for platinum-based doublet chemotherapy
• Adequate hematologic and end-organ function
• Use of appropriate contraceptive methods
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 190
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 600

Exclusion Criteria

• Squamous cell CUP
• Patients with any of the specific non-CUP neoplasms identified in the ESMO CUP guidelines, including:
Non-epithelial cancer and extra gonadal germ-cell tumor
• Patients belonging to any of the following subsets of CUP with favorable prognoses: Poorly differentiated carcinoma with midline distribution, Women with papillary adenocarcinoma of the peritoneal cavity and 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, Patients with a single, small, potentially resectable tumor, Colon cancer-type CUP
• Known presence of brain or spinal cord metastasis, as determined by CT or magnetic resonance imaging evaluation during screening
• History or known presence of leptomeningeal disease
• Uncontrolled or symptomatic hypercalcemia
• Known clinically significant history of liver disease consistent with Child-Pugh Class B or C, including active viral or other hepatitis, current alcohol abuse, or cirrhosis and human immunodeficiency virus infection
• Positive for hepatitis C virus antibody and hepatitis B surface antigen, and active tuberculosis at screening
• Significant cardiovascular disease within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
• History of malignancy other than CUP within 5 years prior to screening
• Prior allogeneic stem cell or solid organ transplantation
• Known allergy or hypersensitivity to any component of the platinum-doublet chemotherapy
• Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or for up to 24 months after the last dose of treatment