A Multinational, Randomized, Double-Blind Study, Comparing the Efficacy of Aflibercept Once Every 2 Weeks versus Placebo in Patients Treated with Gemcitabine for Metastatic Pancreatic Cancer.

Phase 1

Conditions: Patients Treated with Gemcitabine for Metastatic Pancreatic Cancer.

Registration Number: EUCTR2007-003476-19-FR

Lead Sponsor: sanofi-aventis recherche & développement

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 630

Inclusion Criteria

- Cytologically or histologically confirmed evidence of epithelial cancer (adenocarcinoma) of the exocrine pancreas.
- Metastatic disease. Patients with measurable and with non-measurable disease (as per RECIST criteria) are eligible.
- No prior chemotherapy for pancreatic disease. Prior irradiation or chemoradiotherapy with 5-fluorouracil, in which 5-FU was used as a radio-sensitizing agent, is allowed if the treatment-free interval is of at least 3 months.
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

- Related to the methodology :
• Chemotherapy or other systemic therapy for pancreatic cancer.
• Less than 42 days elapsed from prior major surgery (28 days from other prior surgery) to the time of randomization. Less than 28 days elapsed from prior radiation therapy.
• Prior treatment with anti-VEGF or VEGF-Receptor-inhibitors.
• Age < 18 years.
• ECOG performance status (PS) of 3-4.
• History of brain metastases, uncontrolled spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease.
• History of another neoplasm. Adequately treated basal cell or squamous cell skin cancers, carcinoma in situ of the cervix, or any other cancer from which the patient has been disease free for > 5 years are allowed.
• Participation in other clinical trial and any concurrent treatment with any investigational drug within 30 days prior to randomization.
• Any of the following events within the 3 months prior to randomization: treatment resistant peptic ulcer disease, erosive oesophagitis or gastritis, grade 3 or 4 gastrointestinal bleeding/hemorrhage, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism, or other uncontrolled thromboembolic event.
• Any of the following events within the 6 months prior to randomization: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft surgery, NYHA class III or IV congestive heart failure, stroke or transient ischemic attack.
• Occurrence of deep vein thrombosis within 4 weeks prior to randomization.
• Known human immunodeficiency virus (HIV) infection requiring antiretroviral treatment or acquired immunodeficiency-syndrome (AIDS)-related illness.
• Other severe acute or chronic medical condition, which could impair the ability of the patient to participate to the study or to interfere with interpretation of study results.
• Absence of signed and dated Institutional Review Board (IRB)-/Independent Ethical Committee (IEC)-approved patient informed consent form prior to enrollment into the study.
• Pregnant or breast-feeding woman. Positive serum or urine pregnancy test for women of reproductive potential prior to randomization.
• Patient with reproductive potential (male, female) who do not agree to use accepted and effective method of contraception during the study treatment period and for at least 3 months after the completion of the study treatment. The definition of effective method of contraception” will be based on the investigator’s judgment.

- Related to aflibercept
• Urine Protein-Creatinine Ratio (UPCR) > 1 on morning spot urinalysis or proteinuria > 500 mg/24h.
• Serum Creatinine > 1.5 x upper limit of normal (ULN). If creatinine 1.0 - 1.5 x ULN, creatinine clearance, calculated according to Cockcroft-Gault formula < 60 mL/min will exclude the patient.
• Uncontrolled hypertension defined as blood pressure > 150/100 mmHg (= grade 2 according to NCI CTCAE v. 3.0), or systolic blood pressure >180 mmHg if diastolic blood pressure < 90 mmHg, on at least 2 repeated determination on separate days within 3 months prior to study enrollment.
• Patients on anticoagulants therapy with unstable dose of warfarin and/or having an out-of-therapeutic range INR (>3) within the 4 weeks prior to randomization.
• Evidence of clinically significant bleeding diathesis, non-healing wound or underlying coagulopathy (e.g. INR>1.5 without vitamin K antagonist therapy…).

- Related to Gemcitabine
• Absolute neutrophil c

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To demonstrate improvement in overall survival (OS) with aflibercept by comparison to placebo in patients treated with gemcitabine as first line treatment for metastatic pancreatic cancer.;Primary end point(s): Overall Survival (OS), defined as the time interval from the date of randomization to the date of death due to any cause.;Secondary Objective: - To compare in the two treatment arms (by sequential order of statistical analysis):<br>•Progression Free Survival (PFS),<br>•Clinical Benefit assessed by Time to symptoms worsening (TTSW) and improvement in tumor related symptoms,<br>•Overall Response Rate (ORR) in patients with measurable disease at study entry (as per RECIST criteria). <br>- To assess the overall safety in the two treatment arms.<br>- To assess immunogenicity of aflibercept.<br>- To perform population pharmacokinetics in all patients randomized in selected centres.

Secondary Outcome Measures

Name	Time	Method

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