Completed

CUPISCOTargeted Therapy vs. Chemotherapy for Cancer of Unknown Primary Site

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Study Aim

This study aims to evaluate the effectiveness of targeted therapy compared to chemotherapy in improving progression-free survival in patients with cancer of an unknown primary site.

What is being tested

Alectinib

+ Vismodegib

+ Ipatasertib

Drug
Who is being recruted

Neoplasm Metastasis+3

+ Neoplasms

+ Neoplasms, Unknown Primary

Over 18 Years
See all eligibility criteria
How is the trial designed

Treatment Study

Phase 2
Interventional
Study Start: July 2018
See protocol details

Summary

Principal SponsorHoffmann-La Roche
Last updated: January 28, 2026
Sourced from a government-validated database.Claim as a partner

Study start date: July 10, 2018

Actual date on which the first participant was enrolled.

This clinical trial aims to evaluate the effectiveness and safety of two different treatment approaches for patients with cancer of unknown primary site (CUP), a condition where the original tumor location is not identified. The study focuses on patients who have already received three cycles of chemotherapy containing platinum and have shown some disease control. Researchers are comparing the traditional chemotherapy method to a more personalized treatment approach, which uses genetic profiling to guide therapy decisions. This study is important because it could lead to more effective treatment strategies for patients with CUP, potentially improving their outcomes and quality of life. Participants in this study will be randomly assigned to receive either the standard platinum-based chemotherapy or a targeted therapy guided by their unique genetic profile. The targeted therapy or cancer immunotherapy is administered based on specific genetic markers found in the patient's tumor. The main goal is to measure how long the patients live without their cancer worsening, known as progression-free survival. The effectiveness of each treatment will be assessed by investigators using established criteria to evaluate tumor response. While the study aims to find a more effective treatment, participants may experience typical chemotherapy side effects or, in the case of targeted therapy, side effects specific to the drugs used. The hope is to discover whether personalized treatment provides better results compared to the traditional approach.

Official TitleA 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
NCT03498521
Principal SponsorHoffmann-La Roche
Last updated: January 28, 2026
Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.
Design Details

529 patients to be enrolled

Total number of participants that the clinical trial aims to recruit.

Treatment Study

These studies test new ways to treat a disease, condition, or health issue. The goal is to see if a new drug, therapy, or approach works better or has fewer side effects than existing options.



Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria

Any sex

Biological sex of participants that are eligible to enroll.

Over 18 Years

Range of ages for which participants are eligible to join.

Healthy volunteers not allowed

If individuals who are healthy and do not have the condition being studied can participate.

Conditions

Pathology

Neoplasm MetastasisNeoplasmsNeoplasms, Unknown PrimaryNeoplastic ProcessesPathologic ProcessesPathological Conditions, Signs and Symptoms

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

Study Plan

Find out more about all the medication administered in this study, their detailed description and what they involve.
Treatment Groups
Study Objectives

2 intervention groups are designated in this study

This study does not include a placebo group 

Treatment Groups

Group I

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

Group II

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

Study Objectives

Primary Objectives

Secondary Objectives

Study Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.

This study has 125 locations

Suspended

Freeman Hospital

Newcastle upon Tyne, United KingdomOpen Freeman Hospital in Google Maps
Suspended

Southampton General Hospital

Southampton, United Kingdom
Suspended

Torbay Hospital

Torquay, United Kingdom
Suspended

Blacktown Hospital

Blacktown, Australia
Completed125 Study Centers