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 (CUPISCO)

Roche

Status and phase: Active, not recruiting; Phase 2

Conditions: Cancer of Unknown Primary Site

Treatments: Drug: Atezolizumab; Drug: Bevacizumab; Drug: Ivosidenib; Drug: Trastuzumab Subcutaneous (SC); Drug: Entrectinib; Drug: Cobimetinib; Drug: Paclitaxel; Drug: Vemurafenib; Drug: Gemcitabine; Drug: Ipatasertib; Drug: Cisplatin; Drug: Pertuzumab; Drug: Alectinib; Drug: Erlotinib; Drug: Pemigatinib; Drug: Vismodegib; Drug: Carboplatin; Drug: Olaparib

Study type: Interventional

Funder types: Industry; Other

Identifiers

NCT03498521

MX39795

2017-003040-20 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 528 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

528 participants in 2 patient groups

Molecularly-Guided Therapy

Experimental group

Description:

Participants will be assigned to molecularly-guided therapy based on genomic profile.

Treatment:

Drug: Olaparib

Drug: Vismodegib

Drug: Pemigatinib

Drug: Erlotinib

Drug: Alectinib

Drug: Pertuzumab

Drug: Ipatasertib

Drug: Paclitaxel

Drug: Cobimetinib

Drug: Vemurafenib

Drug: Entrectinib

Drug: Trastuzumab Subcutaneous (SC)

Drug: Ivosidenib

Drug: Bevacizumab

Drug: Atezolizumab

Platinum-Based Chemotherapy

Active Comparator group

Description:

Participants will receive platinum-based chemotherapy (Carboplatin or Cisplatin in combination with Gemcitabine or Paclitaxel).

Treatment:

Drug: Carboplatin

Drug: Cisplatin

Drug: Pertuzumab

Drug: Gemcitabine

Drug: Paclitaxel

Drug: Trastuzumab Subcutaneous (SC)