Trial Comparing a Strategy Based on Molecular Analysis to the Empiric Strategy in Patients With CUP

Study Overview
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Brief Summary
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This is a european randomised, phase III, multi-centric study comparing a diagnostic and therapeutic strategy based on molecular analysis followed by suspected primary cancer tailored specific therapy, to an empiric strategy in patients with carcinoma of unknown primary. The purpose of this trial is to determine whether or not a strategy based on molecular analysis is effective in improving the progression free survival rates of patients with carcinoma of unknown primary (CUP).

Official Title
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A Randomised Phase III Trial Comparing a Strategy Based on Molecular Analysis to the Empiric Strategy in Patients With Carcinoma of an Unknown Primary (CUP)

Conditions
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Neoplasms, Unknown Primary

Intervention / Treatment
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* Other: Cancer Type ID test
* Other: No test Empiric strategy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients presenting with carcinoma of unknown primary, confirmed by histopathological analysis (including an immunohistochemical analysis) and corresponding to one of the following histologic types : moderately or well-differentiated adenocarcinoma, poorly-differentiated adenocarcinoma, undifferentiated carcinoma, squamous-cell carcinoma Diagnostic work-up in keeping with Standard Options Recommandations des CAPI (Lesimple et al., 2003), Age > 18 years, Performance Status 0, 1 or 2 according to ECOG Good or poor prognosis CUP classified according to the GEFCAPI classification CUP with at least one measurable lesion Tumour sample available for molecular analysis CUP not belonging to a subgroup requiring a specific treatment, Satisfactory haematological, renal and hepatic function Cardiac, respiratory and neurological function compatible with the administration of cisplatin chemotherapy, No previous chemotherapy for a CUP Previous radiotherapy is acceptable, but it should be completed at least 4 weeks before the start of systemic treatment. Randomization can be performed during this time frame. All patients with reproductive potential must practice an effective method of birth control throughout the study. Female patients with childbearing potential must have a negative pregnancy test within 7 days before study treatment Information delivered to patient and informed consent form signed by the patient or legal representative. Exclusion Criteria: Patients in whom the diagnosis has not been histologically confirmed (a cytological analysis alone does not permit patient entry onto the trial), Patients with known HIV infection Patients with symptomatic brain metastases, Associated disease likely to prevent the patient from receiving the treatment, Previous history of cancer (excepted skin basocellular epithelioma or epithelioma in situ of the uterine cervix) during the 5 years before study entry, Patients already included in another clinical trial with an experimental therapy, Pregnant woman or woman who are breastfeeding, Compliance with trial medical follow-up impossible due to geographic, social or psychological reasons.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: test-guided strategy<br>Treatment considered as the standard at the time of patient inclusion based on the primary cancer suspected by the BioTheranostics Cancer Type ID test molecular analysis | Other: Cancer Type ID test<br>* CancerTYPE ID is a real-time RT-PCR assay that measures and interprets the differential expression of 92 genes as a molecular correlate for tumor classification. The test classifies 28 main tumor types and 50 subtypes using an algorithm incorporating gene expression data from a reference database of 2,094 tumor specimens. CancerTYPE ID is used, in conjunction with other clinical and diagnostic procedures, to help identify tumor type and histological subtype. The performance characteristics and reproducibility of the test have been published previously (Erlander et al., 2011 ; Kerr et al., 2012). CancerTYPE ID is conducted on formalin-fixed paraffin-embedded (FFPE) tumor specimens at bioTheranostics' high complexity laboratory, which is certified by Clinical Laboratory Improvement Amendments (CLIA), accredited by the College of American Pathologists (CAP), and approved by the State of New York.<br>|
| Active Comparator: Empiric strategy<br>Gemcitabine/Cisplatin | Other: No test Empiric strategy<br>* Empiric strategy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival | Progression according to RECIST criteria or death of any cause. | From date of randomization until the date of first progression or date of death from any cause, whichever came first, assessed up to 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate | Response will be assessed using RECIST criteria | An expected average of 1 year | 
| Tolerance (Toxicity grade III and IV, toxic death) | Toxicity will be assessed using NCI-CTC criteria version 4.0 | An expected average of 1 year | 
| Overall survival | Death of any cause | From the day of randomization to death or last date of follow-up, assessed up to 18 months |