Trial Comparing a Strategy Based on Molecular Analysis to the Empiric Strategy in Patients With CUP (GEFCAPI04)

• Response rate [ Time Frame: An expected average of 1 year ] [ Designated as safety issue: No ]
  Response will be assessed using RECIST criteria
• Tolerance (Toxicity grade III and IV, toxic death) [ Time Frame: An expected average of 1 year ] [ Designated as safety issue: No ]
  Toxicity will be assessed using NCI-CTC criteria version 4.0
• Overall survival [ Time Frame: From the day of randomization to death or last date of follow-up, assessed up to 18 months ] [ Designated as safety issue: No ]
  Death of any cause

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).

• Other: TOO Pathwork test
  Molecular test The pathwork Tissue of origin test is a microarray and analytics test that uses gene expression to quantify the similarity of gene expression pattern of poorly differentiated, undifferentiated and metastatic tumor specimens to the gen expression patterns of 15 cancers.
• Other: No test Empiric strategy
  Empiric strategy

• Experimental: test-guided strategy
  Treatment considered as the standard at the time of patient inclusion based on the primary cancer suspected by the Pathwork Tissue Of Origin (TOO) molecular analysis
  Intervention: Other: TOO Pathwork test
• Active Comparator: Empiric strategy
  Gemcitabine/Cisplatin
  Intervention: Other: No test Empiric strategy

Inclusion Criteria:

1. Patients presenting with carcinoma of unknown primary, confirmed by histo-pathological 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
2. Diagnostic work-up in keeping with Standard Options Recommandations des CAPI (Lesimple et al., 2003),
3. Age > 18 years,
4. Performance Status 0, 1 or 2 according to ECOG
5. Good or poor prognosis CUP classified according to the GEFCAPI classification, with at least one measurable lesion
6. Tumour sample available for molecular analysis
7. CUP not belonging to a subgroup requiring a specific treatment,
8. Satisfactory haematological, renal and hepatic function
9. Cardiac, respiratory and neurological function compatible with the administration of cisplatin chemotherapy,
10. No previous chemotherapy,
11. Previous radiotherapy completed at least 4 weeks earlier,
12. 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
13. Information delivered to patient and informed consent form signed by the patient or legal representative.

Exclusion Criteria:

1. Patients in whom the diagnosis has not been histologically confirmed (a cytological analysis alone does not permit patient entry onto the trial),
2. Patients with known HIV infection
3. Patients with symptomatic brain metastases,
4. Associated disease likely to prevent the patient from receiving the treatment,
5. Previous history of cancer (excepted skin basocellular epithelioma or epithelioma in situ of the uterine cervix) during the 5 years before study entry,
6. Patients already included in another clinical trial with an experimental therapy,
7. Pregnant woman or woman who are breastfeeding,
8. Compliance with trial medical follow-up impossible due to geographic, social or psychological reasons.