A Multicenter, Single Arm, Open Label Clinical Trial Evaluating Safety and Health Related Quality of Life of Aflibercept in Combination With Irinotecan/5FU Chemotherapy (FOLFIRI) in Patients With Metastatic Colorectal Cancer (mCRC) Previously Treated With an Oxaliplatin-Containing Regimen
- Histologically or cytologically proven adenocarcinoma of the colon or rectum
- Metastatic disease
- Age ≥18 years
- ECOG PS 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 following the last administration of the oxaliplatin based chemotherapy.
Patients relapsing within 6 months of completion of oxaliplatin adjuvant chemotherapy
are also eligible.
- Patients must be affiliated to a Social Security System.
Related to Methodology
- Prior therapy with irinotecan oAbsolute neutrophil counts (ANC) < 1.5 x 109/L
oPlatelet count < 100 x 109/L oHemoglobin < 9.0 g/dL oTotal bilirubin >1.5 x ULN
oTransaminases >3 x ULN (unless liver metastasis are present, 5 x ULN in that case)
oAlkaline phosphatase >3 x ULN (unless liver metastasis are present, 5 x ULN in that
- Less than 4 weeks elapsed from prior radiotherapy or prior chemotherapy or major
surgery to the time of inclusion or until the surgical wound is fully healed
whichever came later (48 hours in case of minor surgical procedure or until wound
full healing observed).
- Treatment with any investigational drug within 30 days prior to inclusion.
- Adverse events (with exception of alopecia, peripheral sensory neuropathy and those
listed in specific exclusion criteria) from any prior anti cancer therapy of grade >1
[NCI CTCAE] v.4.0) at the time of inclusion.
- History of brain metastases, uncontrolled spinal cord compression, or carcinomatous
meningitis or new evidence of brain or leptomeningeal disease.
- Other prior malignancy. Basal cell or squamous cell skin cancer, carcinoma in situ of
the cervix or any other cancer from which the patient has been disease free for > 5
years are allowed.
- Any of the following within 6 months prior to inclusion: myocardial infarction,
severe/unstable angina pectoris, coronary/peripheral artery bypass graft, NYHA class
III or IV congestive heart failure, stroke or transient ischemic attack.
- Any of the following within 3 months prior to inclusion: Grade 3-4 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 inclusion.
- Known AIDS-related illnesses or known HIV disease requiring antiretroviral treatment.
- Any 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
- Pregnant or breast-feeding women. Positive pregnancy test for women of reproductive
- Patient with reproductive potential (female and male) who do not agree to use a
method of contraception during the study treatment period and for at least 6 months
following completion of study treatment. The definition of effective method will be
left to the investigator's judgment.
Related to Aflibercept:
- Urine protein-creatinine ratio (UPCR) >1 on morning spot urinalysis or proteinuria >
- Serum creatinine > 1.5 x ULN . If creatinine 1.0-1.5 x ULN, creatinine clearance,
calculated according to Cockroft-Gault formula, < 60 ml/min will exclude the patient.
- Uncontrolled hypertension (blood pressure > 140/90 mmHg or systolic blood pressure
>160 mmHg when diastolic blood pressure < 90 mmHg, on at least 2 repeated
determinations on separate days, or upon clinical judgement within 3 months prior to
- Patients on anticoagulant therapy with unstable dose of warfarin and/or having an
out-of-therapeutic range INR (>3) within the 4 weeks prior to inclusion.
- Evidence of clinically significant bleeding diathesis or underlying coagulopathy
(e.g. INR>1.5 without vitamine K antagonist therapy), non-healing wound.
Related to FOLFIRI
- Known DHPD deficiency
- Predisposing colonic or small bowel disorders in which the symptoms were uncontrolled
as indicated by baseline of > 3 loose stools daily.
- Prior history of chronic enteropathy, inflammatory enteropathy, chronic diarrhea,
unresolved bowel obstruction/sub-obstruction, more than hemicolectomy, extensive
small intestine resection with chronic diarrhea.
- History of anaphylaxis or known intolerance to atropine sulphate or loperamide or
appropriate antiemetics to be administered in conjunction with FOLFIRI
- Treatment with concomitant anticonvulsivant agents that are CYP3A4 inducers
(phenytoin, phenobarbital, carbamazepine), unless discontinued >7 days.
- Patients with known Gilbert's syndrome.
The above information is not intended to contain all considerations relevant to a
patient's potential participation in a clinical trial.