Study Of FOLFIRI Chemotherapy With Or Without Sunitinib In Patients With Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the safety and efficacy of FOLFIRI (Irinotecan, Leucovorin and 5 Fluorouracil) chemotherapy when combined with sunitinib or FOLFIRI chemotherapy without adding sunitinib as the first line treatment of patients with metastatic colorectal cancer.

Detailed Description
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On June 25, 2009, the independent Data Monitoring Committee (DMC) reviewed the progress of Study A6181122. The DMC determined Study A6181122 had met pre-specified futility criteria and was unlikely to meet its primary endpoint to demonstrate a statistically significant improvement in progression-free survival (PFS) in patients treated with sunitinib plus FOLFIRI versus placebo plus FOLFIRI. No new safety findings were noted. Pfizer notified clinical trial investigators involved in the study and regulatory agencies of these findings. Patients receiving benefit on treatment as determined by the investigator may remain on study.

Official Title
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A Multicenter, Randomised, Double-Blind, Phase 3 Study Of Sunitinib In Metastatic Colorectal Cancer Patients Receiving Irinotecan, 5-Fluorouracil And Leucovorin (FOLFIRI) As First Line Treatment

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: 5 fluorouracil
* Drug: irinotecan
* Drug: levo- leucovorin
* Drug: sunitinib
* Drug: 5 fluorouracil
* Drug: irinotecan
* Drug: levo- leucovorin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed (histologically or cytologically) colorectal adenocarcinoma with metastatic disease. Not received previous therapy for metastatic colorectal disease but for whom FOLFIRI treatment is clinically indicated. Adequate organ function defined by blood test. Exclusion Criteria: History of another primary cancer in the last 3 years. Previous full field radiotherapy within the last 4 weeks or limited field radiotherapy within 2 weeks of enrolling into the study. Or previous radiation treatment of more that 30% of the bone marrow. History of presence of brain metastasis, spinal cord compression carcinomatous meningitis or leptomeningeal disease.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: 5 fluorouracil<br>* 400mg/m2 bolus injection day 1 followed by 2400mg/m2 continuous infusion for 46 hours every 14 days<br>Drug: irinotecan<br>* 180mg/m2 iv day 1 every 14 days<br>Drug: levo- leucovorin<br>* 200mg/m2 iv; day 1 every 14 days<br>Drug: sunitinib<br>* 37.5mg of blinded therapy every day for 28 days followed by 14 days of blinded therapy free period<br>|
| Placebo Comparator: 2<br> | Drug: 5 fluorouracil<br>* 400mg/m2 bolus injection day 1 followed by 2400mg/m2 continuous infusion for 46 hours every 14 days<br>Drug: irinotecan<br>* 180mg/m2 iv day 1 every 14 days<br>Drug: levo- leucovorin<br>* 200mg/m2 iv; day 1 every 14 days<br>Drug: placebo<br>* 37.5mg of blinded placebo therapy every day for 28 days followed by 14 days of blinded therapy free period<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | PFS defined as time from date of randomization to date of first documentation of objective tumour progression or death due to any cause, whichever occurred first. | First dose of study treatment up to 30 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS was defined as the time from randomization to the date of death due to any cause. OS data were censored on the day following the date of the last contact at which the patient was known to be alive. | Baseline up to 30 months | 
| Number of Participants With Overall Confirmed Objective Response | Objective disease response: participants with a confirmed complete response (CR) or partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST). CR was defined as the disappearance of all target lesions. PR was defined as a greater than or equal to 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. | Day 28 of Cycle 1 up to 30 months | 
| Duration of Response (DR) | DR was defined as the time from the first objective documentation of CR or PR that was subsequently confirmed to the first documentation of disease progression or to death due to any cause, whichever occurred first. | Day 28 of Cycle 1 up to 30 months | 
| Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Assessment Inventory of Gastrointestinal Symptoms (MDASI-GI) Symptom Intensity Score | Symptom Intensity score is comprised of the sum of 13 MDASI core items (ie, pain, fatigue, nausea, disturbed sleep, distress, shortness of breath, remembering things, lack of appetite, drowsiness, dry mouth, sadness, vomiting, numbness or tingling). Participant asked to rate severity of each symptom at their worst in past 24 hours; each item rated from 0 to 10, with 0=symptom not present and 10=as bad as you can imagine; lower scores indicated better outcome (range: 0 to 130). | Day 1 of Cycles 1-3 and Day 1 of every odd-numbered cycle thereafter until end of treatment (EOT)/withdrawal | 
| Change From Baseline in MDASI-GI Symptom Interference Score | Symptom Interference score is comprised of the sum 6 function items from MDASI core (general activity, walking, work, mood, relations with other people, and enjoyment of life). Participant asked to rate how much symptoms have interfered in past 24 hours; each item rated from 0 to 10, with 0=did not interfere and 10=interfered completely; lower scores indicated better outcome (range: 0 to 60). | Day 1 of Cycles 1-3 and Day 1 of every odd-numbered cycle thereafter until EOT/withdrawal | 
| Change From Baseline in European Quality of Life (EuroQol) EQ-5D Self-Report Questionnaire | EQ-5D: participant-rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problem); 3 indicates worst health state (eg, confined to bed). Scoring formula developed by EuroQol Group assigns a utility value for each domain. Score is transformed and results in total score range -1.11 to 1.000; higher score indicates better health state. | Day 1 of Cycles 1-3 and Day 1 of every odd-numbered cycle thereafter until EOT/withdrawal | 
| Change From Baseline in EuroQol (EQ) Visual Analog Scale (VAS) (EQ-VAS) | EQ-5D: participant-rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state. | Day 1 of Cycles 1-3 and Day 1 of every odd-numbered cycle thereafter until EOT/withdrawal | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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colorectal neoplasms