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

Conditions: Cancer of Unknown Primary Site

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.


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