Colorectal Cancer Metastatic (AFEQT)

This study is currently recruiting participants.
Verified November 2013 by Sanofi
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01670721
First received: July 13, 2012
Last updated: November 15, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer Metastatic
Drug: AFLIBERCEPT AVE0005
Drug: irinotecan
Drug: fluorouracil
Drug: Leucovorin
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Number of participants reporting Adverse Events [ Time Frame: up to a maximum of 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Health Related Quality of Life (HRQL) assessed by using changes from baseline in score derived from the 2 HRQL"questionnaires" [ Time Frame: Every 4 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 200
Study Start Date: August 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Aflibercept

One (1) hour intravenous infusion on Day 1 followed by FOLFIRI (irinotecan, 5-Fluorouracil and leucovorin) administered as follows:

  • dI-leucovorin infusion over 2 hour on Day 1
  • Irinotecan: infusion over 90-minute infusion, on Day 1, followed by bolus 5-FU and 5-FU continuous infusion over 46 hours infusion OR as individualized by physician's clinical judgment.

Treatment cycle to be administered every 2 weeks. Study treatment (aflibercept and FOLFIRI) has to be discontinued upon documentation of disease progression.

If FOLFIRI is permanently discontinued, then aflibercept should be continued until disease progression or unacceptable toxicity or patient's refusal of further treatment.

If aflibercept is permanently discontinued, then FOLFIRI can be continued until disease progression or unacceptable toxicity or patient's refusal of further treatment.

The end of treatment will be the date of the last treatment administration, either aflibercept or FOLFIRI whichever comes last

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

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01670721

Contacts
Contact: Trial Transparency Team Contact-US@sanofi-aventis.com

Locations
France
Administrative office Recruiting
Paris, France
Sponsors and Collaborators
Sanofi
Regeneron Pharmaceuticals
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01670721     History of Changes
Other Study ID Numbers: AFLIBL06266, 2012-000048-89, U1111-1128-9325
Study First Received: July 13, 2012
Last Updated: November 15, 2013
Health Authority: France: Institutional Ethical Committee

Additional relevant MeSH terms:
Colorectal Neoplasms
Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Fluorouracil
Irinotecan
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Antidotes
Protective Agents

ClinicalTrials.gov processed this record on April 21, 2014