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 recieved 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-CY
• Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-01-14
• Last Update Posted: 5 April 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 790

Inclusion Criteria

• Age >=18 years
• Histologically-confirmed unresectable poor-risk or unfavorable prognosis subset of CUP as defined by European Society for Medical Oncology 2015 clinical practice guidelines for 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 <=4 months old at Screening that is expected to be sufficient for generation of a comprehensive genomic profile using Foundation Medicine tissue biopsy assayat a central reference pathology laboratory
• Availability of local pathology reports confirming compatibility with CUP diagnosis and the associated slides used for the diagnosis. If the slides used for the local test confirming local CUP diagnosis are not available, an FFPE block must be submitted that is sufficient to allow for central confirmation of CUP diagnosis
• No prior systemic therapy for the treatment of CUP
• ECOG performance status of 0 or 1
• Life expectancy >=12 weeks
• Eligible for platinum-based chemotherapy
• Adequate hematologic and end-organ function
• For women of childbearing potential: agreement to remain abstinent or use contraception with a failure rate of <1% per year during the treatment period and after the final dose of study treatment for at least:
– 2 weeks for erlotinib
– 1 month for ipatasertib and olaparib
– 3 months for alectinib and entrectinib
– 5 months for atezolizumab
– 6 months for bevacizumab, cobimetinib, vemurafenib, carboplatin, cisplatin, paclitaxel and gemcitabine,
– 7 months for trastuzumab and pertuzumab
– 24 months for vismodegib
Women must refrain from donating eggs during this same period
• For men with a female partner of childbearing potential who is not pregnant must remain abstinent or use a condom plus an additional contraception that together result in a failure rate of <1% per year during the treatment period and after the final dose of study treatment for at least:
2 weeks for erlotinib
1 month for ipatasertib
2 months for vismodegib
3 months for alectinib and entrectinib
6 months for bevacizumab, cobimetinib, vemurafenib, carboplatin, cisplatin, paclitaxel and gemcitabine
7 months for trastuzumab and pertuzumab
Men must refrain from donating sperm during this same period
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
• Histology and immunohistology profiles that are not adenocarcinoma or poorly differentiated carcinoma / adenocarcinoma, i.e., non-epithelial cancer, extragonadal germ-cell tumor, neuroendocrine tumors, sarcoma, melanoma, mesothelioma, hematologic malignancies (list is not limitative)
• Patient with an immunohistochemistry profile that provides a definitive clinical indication of a primary
cancer with a specific treatment
• 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, 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, Patients with a single, small, potentially resectable tumor, Colon cancer-type CUP (including patients with a CK7 negative, CK20 positive, CDX-2 positive immunohistochemistry profile)
• 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
• Human immunodeficiency virus infection
• Positive for hepatitis C virus antibody and hepatitis B surface antigen (HBsAg) at screening. If HBsAg test is negative but total hepatitis B core antibody test (HBcAb) is positive, hepatitis B virus DNA must be performed and if positive, this will be an exclusion criterion
• Active tuberculosis at screening
• Active infections requiring intravenous antibiotics
• Significant cardiovascular disease within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
• Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment
• History of malignancy other than CUP within 5 years prior to screening
• Prior allogeneic stem cell or solid organ transplantation

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified