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

• Register: ClinicalTrials.gov
• Last refreshed on: 27 November 2023
• Main ID: NCT03498521
• Date of registration: 05/04/2018
• Prospective Registration: Yes
• Primary sponsor: Hoffmann-La Roche
• Public title: 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
• Scientific title: 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
• Date of first enrolment: July 10, 2018
• Target sample size: 790
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03498521
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Australia, Austria, Brazil, Bulgaria, Chile, Colombia, Croatia, Cyprus, Czechia, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Japan, Kazakhstan, Korea, Republic of, Latvia, Mexico, Netherlands, Norway, Peru, Poland, Portugal, Romania, Spain, Switzerland, Thailand, Turkey, United Kingdom

Contacts

• Name: Clinical Trials
• Affiliation: Hoffmann-La Roche

Key inclusion & exclusion 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 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Cancer of Unknown Primary Site

Intervention(s)

Drug: Atezolizumab

Drug: Paclitaxel

Drug: Vismodegib

Drug: Bevacizumab

Drug: Pemigatinib

Drug: Carboplatin

Drug: Gemcitabine

Drug: Cobimetinib

Drug: Entrectinib

Drug: Trastuzumab Subcutaneous (SC)

Drug: Erlotinib

Drug: Ipatasertib

Drug: Pertuzumab

Drug: Vemurafenib

Drug: Alectinib

Drug: Cisplatin

Drug: Ivosidenib

Drug: Olaparib

Primary Outcome(s)

Progression Free Survival (PFS1) [Time Frame: From randomization to the first occurrence of disease progression as assessed by the investigator according to Response Evaluation Criteria In Solid Tumors v1.1 (RECIST v1.1) or death from any cause, through the end of study (approximately 70 months)]

Secondary Outcome(s)

Overall Survival (OS) [Time Frame: From randomization to death from any cause, through the end of study (approximately 70 months)]

Duration of Response (DOR1) [Time Frame: From the first documentation of a complete response (CR) or partial response (PR) to disease progression or death from any cause, whichever occurs first (up to approximately 70 months)]

Disease Control Rate (DCR1) [Time Frame: From randomization to death from any cause, through the end of study (approximately 70 months)]

Objective Response Rate (ORR1) [Time Frame: Two consecutive occurrences of complete or partial response >/=4 weeks apart]

Percentage of Participants with Adverse Events (AEs) [Time Frame: From baseline through the end of study (approximately 70 months)]

Secondary ID(s)

MX39795

2017-003040-20

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Foundation Medicine, Inc.