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

This study has been completed.
Sponsor:
Information provided by:
Pfizer
ClinicalTrials.gov Identifier:
NCT00457691
First received: April 4, 2007
Last updated: June 9, 2011
Last verified: June 2011
  Purpose

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.


Condition Intervention Phase
Metastatic Colorectal Cancer
Drug: 5 fluorouracil
Drug: irinotecan
Drug: levo- leucovorin
Drug: sunitinib
Drug: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Progression-free Survival (PFS) [ Time Frame: First dose of study treatment up to 30 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: Baseline up to 30 months ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Overall Confirmed Objective Response [ Time Frame: Day 28 of Cycle 1 up to 30 months ] [ Designated as safety issue: No ]
    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.

  • Duration of Response (DR) [ Time Frame: Day 28 of Cycle 1 up to 30 months ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Assessment Inventory of Gastrointestinal Symptoms (MDASI-GI) Symptom Intensity Score [ Time Frame: Day 1 of Cycles 1-3 and Day 1 of every odd-numbered cycle thereafter until end of treatment (EOT)/withdrawal ] [ Designated as safety issue: No ]
    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).

  • Change From Baseline in MDASI-GI Symptom Interference Score [ Time Frame: Day 1 of Cycles 1-3 and Day 1 of every odd-numbered cycle thereafter until EOT/withdrawal ] [ Designated as safety issue: No ]
    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).

  • Change From Baseline in European Quality of Life (EuroQol) EQ-5D Self-Report Questionnaire [ Time Frame: Day 1 of Cycles 1-3 and Day 1 of every odd-numbered cycle thereafter until EOT/withdrawal ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in EuroQol (EQ) Visual Analog Scale (VAS) (EQ-VAS) [ Time Frame: Day 1 of Cycles 1-3 and Day 1 of every odd-numbered cycle thereafter until EOT/withdrawal ] [ Designated as safety issue: No ]
    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.


Enrollment: 768
Study Start Date: June 2007
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: 5 fluorouracil
400mg/m2 bolus injection day 1 followed by 2400mg/m2 continuous infusion for 46 hours every 14 days
Drug: irinotecan
180mg/m2 iv day 1 every 14 days
Drug: levo- leucovorin
200mg/m2 iv; day 1 every 14 days
Drug: sunitinib
37.5mg of blinded therapy every day for 28 days followed by 14 days of blinded therapy free period
Placebo Comparator: 2 Drug: 5 fluorouracil
400mg/m2 bolus injection day 1 followed by 2400mg/m2 continuous infusion for 46 hours every 14 days
Drug: irinotecan
180mg/m2 iv day 1 every 14 days
Drug: levo- leucovorin
200mg/m2 iv; day 1 every 14 days
Drug: placebo
37.5mg of blinded placebo therapy every day for 28 days followed by 14 days of blinded therapy free period

Detailed Description:

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.

  Eligibility

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

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00457691

  Show 130 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided by Pfizer

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer Inc
ClinicalTrials.gov Identifier: NCT00457691     History of Changes
Other Study ID Numbers: A6181122
Study First Received: April 4, 2007
Results First Received: March 9, 2011
Last Updated: June 9, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
colorectal neoplasms

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Fluorouracil
Irinotecan
Sunitinib
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

ClinicalTrials.gov processed this record on July 22, 2014