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 recieved three cycles of platinum doublet chemotherapy

Phase 1

• Conditions: Cancer of Unknown Primary Site; MedDRA version: 20.0Level: LLTClassification code 10032248Term: Other malignant neoplasm of unspecified siteSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-003040-20-FI
• Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-05-07
• Last Update Posted: 4 April 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 790

Inclusion Criteria

• Age >=18 years
• Histologically-confirmed unresectable poor-risk or unfavorable prognosis subset of CUP as defined by European Society for Medical Oncology 2015 clinical practice guidelines for CUP
• At least one lesion that is measurable according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
• Availability of a tumor Formalin-fixed paraffin-embedded (FFPE) block <=4 months old at the start of creening that is expected to be sufficient and suitable (in quantity and quality) for generation of comprehensive genomic profile using Foundation medicine tissue biopsy assay at a central reference pathology laboratory
• Availability of local pathology reports confirming compatibility with CUP diagnosis and the associated slides used for the diagnosis. If the slides used for the local test confirming local CUP diagnosis are not available, an FFPE block must be submitted that is sufficient to allow for central confirmation of CUP diagnosis
• No prior systemic therapy for the treatment of CUP
- Prior local intratumoral therapy may be accepted. If prior local intratumoral therapy, at least one of the measurable lesion(s) must have not benefited from local intratumoral therapy
• ECOG performance status of 0 or 1
• Life expectancy >=12 weeks
• Eligible for platinum-based chemotherapy
• Adequate hematologic and end-organ function
• Agrees to use protocol defined methods of contraception
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 190
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 600

Exclusion Criteria

• Squamous cell CUP
• Patients with histology and immunohistology profiles (per 2015
ESMO guidelines) that are not adenocarcinoma
or poorly differentiated carcinoma / adenocarcinoma, i.e., non-epithelial
cancer, extragonadal germ-cell tumor, neuroendocrine tumors, sarcoma,
melanoma, mesothelioma, hematologic malignancies (list is not
limitative)
• Patient with an immunohistochemistry profile that provides a
definitive clinical indication of a primary
cancer with a specific treatment
• Patients 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 are also excluded. These are: 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, patients with a single, small,
potentially resectable tumor, colon cancer-type CUP (including patients
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 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, as determined by
CT or magnetic resonance imaging evaluation during screening
• History or known presence of leptomeningeal disease
• Known clinically significant history of liver disease consistent with
Child-Pugh Class B or C, including active viral or other hepatitis, current
alcohol abuse, or cirrhosis
• Human immunodeficiency virus infection
• Positive for hepatitis C virus antibody at screening. If a patient has a
positive HCV antibody test at screening, an HCV RNA test must also be
performed. A patient will be excluded from the study only if the HCV
antibody and the HCV RNA test are positive. If the HCV antibody test is
positive, but the HCV RNA test is negative, the patient may enroll in the
study
• Positive for hepatitis B surface antigen (HBsAg) at screening. If HBsAg
test is negative but the total hepatitis B core antibody test (HBcAb) is
positive, hepatitis B virus DNA must be performed and if the resulting
HBV DNA test is positive, the patient will be excluded from the study
• Active tuberculosis at screening
• Active infections requiring intravenous antibiotics
• Significant cardiovascular disease within 3 months prior to initiation of
study treatment, unstable arrhythmia, or unstable angina
• History of malignancy within 5 years prior to initiation of study
treatment with the exception of the cancer under investigat

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified