Open-labeled, randomized multi-center phase II study evaluating the efficacy and safety of Paclitaxel/ Carboplatin with and without Cetuximab as first-line treatment of adeno- and undifferentiated carcinoma of unknown primary (CUP)

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 150

Inclusion Criteria

-Histologically or cytologically proven, non-resectable carcinoma of unknown primary (adenocarcinoma or non-differentiated carcinoma)
-Measurable tumor lesion(s) according to RECIST criteria
-WHO PS 0 to 1
-Signed written informed consent
-=18 years of age
-Effective contraception for both male and female subjects if the risk of conception exists
-Adequate bone marrow function: Neutrophil blood cell count (NBC) = 1,5x109/L, platelet count = 100x109/L, hemoglobin = 5,00 mmol/L (8 g/dL)
-Adequate liver and renal function: bilirubin = 1,5 x upper normal level (UNL) and not increasing more than 25% within the last 4 weeks, ASAT and ALAT = 2,5 x UNL or in case of liver metastases = 5 x UNL. Serum creatinine = 1.5 x UNL

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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

-Previous exposure to epidermal growth factor receptor-targeting therapy
-Previous chemotherapy except adjuvant treatment with progression of disease documented > 6 months after end of adjuvant treatment
-Radiotherapy (> 30 Gy) major abdominal or thoracic surgery within the last 4 weeks before inclusion
-Concurrent chronic systemic immunotherapy, chemotherapy or hormone therapy.
-Investigational agents or participation in clinical trials within 30 days before treatment start in this study
-Clinically relevant coronary disease or myocardial infarction within 12 months before study entry
-Possibility of a curative local treatment (surgery and/or radiotherapy)
-Women with axillary node metastasis as predominant tumor site
-Women with peritoneal carcinomatosis as predominant tumor site
-Men < 50 y. with retroperitoneal or mediastinal lymph node +/- lung metastases as predominant tumor site
-Identification of the primary or suspicion of a specific tumor entity by reference histopathology (i.e. Her-2 positive or hormone receptor positive tumors corresponding to breast cancer, CK7-negative/CK20-positive tumors with high probability for colorectal cancer)
-Peripheral neuropathy > CTC grade I
-Previous malignancy within the last 5 years (except history of basal cell carcinoma of skin or pre-invasive carcinoma of the cervix with adequate treatment)
-History of severe psychiatric illness
-Life expectancy less than six weeks
-Drug or alcohol abuse
-Known hypersensitivity reaction to any of the components of the study treatment
-Pregnancy (absence to be confirmed by ß-hCG test) or lactation period
-Brain metastasis and/or leptomeningeal disease (known or suspected)
-Acute or sub-acute intestinal occlusion or inflammatory bowel disease

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the progression free survival rate with Cetuximab/ Paclitaxel/ Carboplatin vs. Paclitaxel/ Carboplatin in patients with carcinoma of unknown primary;Secondary Objective: -Response rate (RR)<br>-Toxicity <br>-Median progression free survival (PFS) <br>-Overall survival (OS) <br>-Rate of secondary diagnosed primary tumors by histopathology<br>-Prognostic and predictive value of results of translational research (including EGFR-, ERCC1-, RRM1-, and TTF1-expression levels, k-ras mutation status, genomic profiling) with regard to treatment efficacy<br>;Primary end point(s): The rate of progression free survival at 8 months after randomization, defined as the proportion of patients alive with stable disease, partial or complete response, according to RECIST is the primary endpoint for the final analysis.

Secondary Outcome Measures