Phase 2
N=529
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
Cancer of Unknown Primary Site
Bottom Line
View on ClinicalTrials.gov: NCT03498521 ↗Enrolled (actual)
529
Serious AEs
34.1%
Results posted
Jun 2024
Primary outcome: Primary: Progression Free Survival (PFS) as Assessed by the Investigator According to Response Evaluation Criteria In Solid Tumors v1.1 (RECIST v1.1) — 6.14; 4.40 Months — p=0.0177
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Alectinib (Drug); Vismodegib (Drug); Ipatasertib (Drug); Olaparib (Drug); Erlotinib (Drug); Bevacizumab (Drug); Vemurafenib (Drug); Cobimetinib (Drug); Trastuzumab Subcutaneous (SC) (Drug); Pertuzumab (Drug); Atezolizumab (Drug); Carboplatin (Drug); Paclitaxel (Drug); Cisplatin (Drug); Gemcitabine (Drug); Entrectinib (Drug); Ivosidenib (Drug); Pemigatinib (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Hoffmann-La Roche
- Primary completion
- Feb 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Progression Free Survival (PFS) as Assessed by the Investigator According to Response Evaluation Criteria In Solid Tumors v1.1 (RECIST v1.1) |
6.14; 4.40 | 0.0177 sig |
| SECONDARY Overall Survival (OS) |
15.18; 12.78 | — |
| SECONDARY Objective Response Rate (ORR) |
4.9; 3.6; 12.9; 4.5; 44.5; 49.1 | — |
| SECONDARY Duration of Response (DOR) |
16.39; NA | — |
| SECONDARY Disease Control Rate (DCR) |
64.7; 60.0 | — |
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
Data sourced from ClinicalTrials.gov (NCT03498521). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.