Colorectal Cancer Metastatic

Colorectal Cancer Metastatic Clinical Trial

— AFEQT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01670721
• Other study ID #: AFLIBL06266
• Secondary ID: 2012-000048-89U1
• Status: Completed
• Phase: Phase 3
• First received: July 13, 2012
• Last updated: August 3, 2015
• Start date: August 2012
• Est. completion date: June 2015

Study information

• Verified date: August 2015
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Institutional Ethical Committee
• Study type: Interventional

Clinical Trial Summary

Primary 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) according to side effects prevention and management guidelines.

Secondary Objective:

To document the Health-Related Quality of Life (HRQL) of aflibercept in this patient population.

Description:

Each patient will be treated until disease progression, unacceptable toxicity, death, Investigator's decision or patient's refusal for further treatment (whichever come first). Patients will be followed-up during treatment and for at least 30 days after its last study treatment (either aflibercept or FOLFIRI) administration, up to a maximum of 6 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 183
• Est. completion date: June 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

• 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.

Exclusion criteria:

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 case)

• 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 results.

• Pregnant or breast-feeding women. Positive pregnancy test for women of reproductive potential.

• 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 > 500 mg/24-h.

• 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 study inclusion.

• 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.

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer Metastatic
• Colorectal Neoplasms
• Neoplasms

Intervention

Drug:
• AFLIBERCEPT AVE0005
Pharmaceutical form:Concentrate for solution for infusion Route of administration: Intravenous
• irinotecan
Pharmaceutical form:Concentrate for solution for infusion Route of administration: Intravenous
• fluorouracil
Pharmaceutical form:Concentrate for solution for infusion Route of administration: Intravenous
• Leucovorin
Pharmaceutical form:Concentrate for solution for infusion Route of administration: Intravenous

Locations

Country	Name	City	State
France	Administrative office	Paris

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Regeneron Pharmaceuticals

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants reporting Adverse Events		up to a maximum of 6 months	Yes
Secondary	Health Related Quality of Life (HRQL) assessed by using changes from baseline in score derived from the 2 HRQL"questionnaires"		Every 4 weeks	No