Clinical trial · Interventional
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
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
NCT03498521CI-TRIAL-00097492CUPISCOcompletedPhase 2Results postedClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Cancer of Unknown Primary Site | Malignant Neoplasm of Unknown Primary | ALIAS | 0.90 |
Interventions
Interventions (18)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Alectinib | Drug | Alectinib | ALIAS |
| Atezolizumab | Drug | Atezolizumab | ALIAS |
| Bevacizumab | Drug | Bevacizumab | ALIAS |
| Carboplatin | Drug | Carboplatin | ALIAS |
| Cisplatin | Drug | Cisplatin | ALIAS |
| Cobimetinib | Drug | Cobimetinib | ALIAS |
| Entrectinib | Drug | Entrectinib | ALIAS |
| Erlotinib | Drug | Erlotinib | ALIAS |
| Gemcitabine |
Design
Arms and outcomes
Arms (2)
- type
- EXPERIMENTAL
- label
- Molecularly-Guided Therapy
- description
- Participants will be assigned to molecularly-guided therapy based on genomic profile.
- interventionNames
- Drug: Alectinib
- Drug: Vismodegib
- Drug: Ipatasertib
- Drug: Olaparib
- Drug: Erlotinib
- Drug: Bevacizumab
- Drug: Vemurafenib
- Drug: Cobimetinib
- Drug: Trastuzumab Subcutaneous (SC)
- Drug: Pertuzumab
- Drug: Atezolizumab
- Drug: Paclitaxel
- Drug: Entrectinib
- Drug: Ivosidenib
- Drug: Pemigatinib
- type
- ACTIVE_COMPARATOR
- label
- Platinum-Based Chemotherapy
- description
- Participants will receive platinum-based chemotherapy (Carboplatin or Cisplatin in combination with Gemcitabine or Paclitaxel).
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
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
References
Publications (1)
- DERIVEDKramer A, Bochtler T, Pauli C, Shiu KK, Cook N, de Menezes JJ, Pazo-Cid RA, Losa F, Robbrecht DG, Tomasek J, Arslan C, Ozguroglu M, Stahl M, Bigot F, Kim SY, Naito Y, Italiano A, Chalabi N, Duran-Pacheco G, Michaud C, Scarato J, Thomas M, Ross JS, Moch H, Mileshkin L. Molecularly guided therapy versus chemotherapy after disease control in unfavourable cancer of unknown primary (CUPISCO): an open-label, randomised, phase 2 study. Lancet. 2024 Aug 10;404(10452):527-539. doi: 10.1016/S0140-6736(24)00814-6. Epub 2024 Jul 31. PMID 39096924