Safety and Quality of Life study of Aflibercept in patients with metastatic Colorectal Cancer previously treated with an oxaliplatin-based regime

• Conditions: Colorectal Neoplasms; MedDRA version: 16.1Level: PTClassification code 10052358Term: Colorectal cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-005724-17-HU
• Lead Sponsor: Sanofi aventis Groupe

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-01-15
• Last Update Posted: 19 May 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 900

Inclusion Criteria

- Histologically or cytologically proven adenocarcinoma of the colon or rectum
- Metastatic disease
- Eastern Cooperative Oncology Group performance status 0-1
- One and only one prior chemotherapeutic regimen for metastatic disease. This prior chemotherapy must be an oxaliplatin containing regimen. Patients must have progressed during or after the oxaliplatin based chemotherapy. Patients relapsed within 6 months of completion of oxaliplatin adjuvant chemotherapy are eligible.
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 300
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 600

Exclusion Criteria

- Prior therapy with irinotecan
- Inadequate bone marrow, liver and renal function: neutrophils < 1.5x109/L, platelets < 100x109/L, hemoglobin < 9.0 g/dL, total bilirubin >1.5 x upper normal limit (ULN), transaminases >3 x ULN (unless liver metastasis are present), alkaline phosphatase >3 x ULN (unless liver metastasis are present), serum creatinine > 1.5 x ULN.
- Less than 4 weeks from prior radiotherapy, prior chemotherapy, prior major surgery (or until the surgical wound is fully healed).
- Treatment with any investigational drug within the prior 30 days.
- Treatment with concomitant anticonvulsivant agents that are CYP3A4 inducers (phenytoin, phenobarbital, carbamazepine), unless discontinued >7 days.
- History of brain metastases, uncontrolled spinal cord compression, or carcinomatous meningitis or new evidence of brain or leptomeningeal disease.
- Prior malignancy (other than colorectal) including prior malignancy from which the patient has been disease free for < 5 years (except adequately treated basal or squamous cell skin cancer or carcinoma in situ of the cervix).
- Any of the following within 6 months prior to study inclusion: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, severe congestive heart failure, stroke or transient ischemic attack.
- Any of the following within 3 months prior study inclusion: severe gastrointestinal bleeding/hemorrhage, treatment resistant peptic ulcer disease, erosive oesophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism or other uncontrolled thromboembolic event.
- Occurrence of deep vein thrombosis within 4 weeks, prior to study inclusion.
- Known dihydropyrimidine dehydrogenase deficiency.
- Predisposing colonic or small bowel disorders in which the symptoms were uncontrolled.
- Prior history of chronic enteropathy, inflammatory enteropathy, chronic diarrhea, unresolved bowel obstruction/sub-obstruction, more than hemicolectomy, extensive small intestine resection with chronic diarrhea.
- Known Gilbert’s syndrome.
- Unresolved or unstable toxicity from any prior anti cancer therapy at the time of inclusion.
- History of anaphylaxis or known intolerance to atropine sulphate or loperamide or appropriate antiemetics to be administered in conjunction with FOLFIRI (irinotecan, 5-Fluorouracil, leucovorin).
- Severe acute or chronic medical condition, which could impair the ability of the patient to participate to the study.
- Urine protein-creatinine ratio (UPCR) >1 on morning spot urinalysis or proteinuria > 500 mg/24-h.
- Uncontrolled hypertension within 3 months prior to study inclusion.
- Patients on anticoagulant therapy with unstable dose of warfarin and/or having an out-of-therapeutic range INR within the 4 weeks prior to study inclusion.
- Evidence of clinically significant bleeding predisposition or underlying coagulopathy, non-healing wound.
- Pregnant or breast-feeding women.
- Patients with reproductive potential who do not agree to use an accepted effective method of contraception.

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 safety of aflibercept in patients with metastatic Colorectal Cancer (mCRC) treated with irinotecan/5FU combination (FOLFIRI) after failure of an oxaliplatin based regimen (patients similar to those evaluated in the VELOUR trial);Secondary Objective: To document the Health-Related Quality of Life (HRQL) of aflibercept in this patient population.<br>;Primary end point(s): - Number of participants reporting adverse events<br>- Number of participants reporting laboratory<br>abnormalities;Timepoint(s) of evaluation of this end point: Up to 30 days after the end of<br>treatment

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Health-Related Quality of Life (HRQL) assessed by<br>using changes from baseline in scores derived from<br>the 3 HRQL questionnaires;Timepoint(s) of evaluation of this end point: Every 4 weeks