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A phase II study of erlotinib and bevacizumab in patients with advanced upper gastrointestinal carcinomas, refractory or intolerable to standard systemic therapy

Conditions
Histologically or cytologically verified upper gastro-intestinal carcinoma, including carcinomas of the esophagus, cardia, stomac, pancreas, gall bladder, and bile ducts of the following histological subtypes: adenocarcinoma, planocellular or squamous cell carcinoma, and anaplastic/high-grade or undifferentiated carcinoma
Registration Number
EUCTR2006-001308-35-DK
Lead Sponsor
The Finsen Center, Rigshospitalet
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
All
Target Recruitment
63
Inclusion Criteria

Histologically or cytologically verified upper gastro-intestinal carcinoma, including carcinomas of the esophagus, cardia, stomac, pancreas, gall bladder, and bile ducts of the following histological subtypes: adenocarcinoma, planocellular or squamous cell carcinoma, and anaplastic/high-grade or undifferentiated carcinoma.
PS 0-2 (ECOG scale)
Age over 18 years
Life expectancy > 3 months
Sufficient organ function, defined as:
Platelets > 100 x 109/liter
Leukocytes > 3,0 x 109/liter
ACN > 1,5 x 109/liter
ASAT and/or ALAT < 3 x upper normal limit
Bilirubin < 1,5 x upper normal limit
EDTA clearance > 45 ml/min
APTT and INR < normal limit
Fertile females must use oral contraceptive, IUD (intrauterine device) or preservatives. Fertile males must use preservatives.

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

Radiotherapy or chemotherapy within the last 4 weeks
Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids
Any prior EGFR- or VEGFR-based therapy
Any condition (medical, social, psychological), which would prevent adequate information and follow-up
Tumor located close to major blood vessels and judged to possess a high risk of serious bleeding
Any other active malignancy, except basal or squamous cell carcinoma of the skin, or carcinoma in situ
Any significant cardiac disease (New York Heart Association Class II or greater), significant arrythmia, congestive heart failure, acute myocardial infarction within 6 months or unstable angina pectoris
Clinically significant peripheral vascular disease
Evidence of coagulapathy
Use of ASA, NSAIDs or clopidogrel
Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to treatment, anticipation of need for major surgical procedure during the curse of the study
Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to treatment
History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 month prior to treatment
Any ongoing infection, uncontrolled diabetes mellitus, serious non-healing wound or ulcer
Pregnancy or breast feeding
Ongoing therapeutic anti-coagulation
Hypertension with blood pressure > 150/100 mmHg

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: To determine the median time to progression (TTP) and response rate (RR) of the combination of erlotinib and bevacizumab in patients with advanced upper gastro-intestinal carcinomas, refractory or intolerant to standard systemic therapy.;Secondary Objective: To determine safety, tolerability and toxicity. <br>To determine median and overall survival (OS).<br>To correlate efficacy of treatment with the expression of tumor markers obtained in serum (EFGR, bFGF, p-VEGF-A, and sVEGF-R2), in paraffin embedded tumor tissue (micro vessel density (MVD), and expression of VEGFR and EGFR, after immunostaining), and in fresh frozen tumor biopsies (micro array-based analyses of patterns of gene expression).<br>;Primary end point(s): median time to progression (TTP) and response rate (RR) <br>safety, tolerability and toxicity. <br>median and overall survival (OS).<br>
Secondary Outcome Measures
NameTimeMethod
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