Clinical trial NCT00337389: Phase III Randomized Study of 5-FU, CoFactor, and Avastin vs. 5-FU, LV and Avastin for First-Line Colorectal Cancer.
Official title: A Phase III Multi-Center Randomized Clinical Trial to Evaluate the Safety and Efficacy of CoFactor and 5-Fluorouracil (5-FU) Plus Bevacizumab Versus Leucovorin and 5-FU Plus Bevacizumab as Initial Treatment for Metastatic Colorectal Carcinoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Metastatic Colorectal Cancer
Colon Cancer
Rectal Cancer
Keywords: Metastatic
Colorectal
Cancer
CoFactor
Stage IV
Lead sponsor: Mast Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2006-06-16
Enrollment: 1200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To compare the progression-free survival time (PFS) in patients treated with 5-FU modulated with CoFactor (plus bevacizumab) to 5-FU modulated with leucovorin (plus bevacizumab) in patients with Metastatic Colorectal Cancer.


Eligibility criteria: Inclusion Criteria:

1. Greater or equal to 18 years of age.
2. Surgically incurable, metastatic disease from proven colon or rectal adenocarcinoma.
3. Life expectancy of at least 3 months.
4. Histologically confirmed metastatic disease. Histological confirmation may be waived if needle biopsy presents a significant risk to the subject and the clinical setting is clinically consistent with metastasis of colorectal cancer, e.g. surgical findings at laparotomy, or positive PET scan, synchronous histologically confirmed primary tumor with typical metastatic pattern (stage D disease). Waiver can only be granted by the Sponsor, and these cases will be kept to less than 10% of the total study population.
5. Measurable disease. At least one unidimensionally measurable lesion with a diameter ≥10 mm using spiral CT scans (use of spiral CT must be documented in medical records and used consistently throughout the study) or ≥20 mm using conventional CT or MRI scans.
6. No prior systemic chemotherapy or immunotherapy for metastatic or advanced local disease. However patients may have had radiosensitizing doses of fluoropyrimidines (only 5-FU or capecitabine, with or without leucovorin or levamisole is permitted) if completed 6 months prior to treatment on this protocol. No prior irinotecan or oxaliplatin in combination with radiotherapy is allowed.
7. Prior adjuvant therapy is allowed if completed more than 6 months prior to treatment on this protocol. Regimens which included oxaliplatin and irinotecan are allowed.
8. ECOG Performance Status is 0-2 or Karnofsky performance level of 100-70.
9. Willing and able to provide written informed consent.

Exclusion Criteria:

1. Any prior exposure to bevacizumab.
2. A known intolerance to fluoropyrimidine (5-FU, capecitabine, floxuridine, UFT) therapy suggestive of dihydropyrimidine dehydrogenase (DPD) deficiency.
3. Use of the following drugs are not permitted on the protocol: sorivudine (or other nucleoside analogue), or Brivudin™ (or other DPD inhibitor).
4. Pregnancy or lactation. Women with a positive (or no) serum or urine pregnancy test within 15 days of Cycle 1 Week 1. Women must have been amenorrheic for at least 12 consecutive months to be considered to lack potential for child bearing.
5. If sexually active and of child-bearing potential, failure to agree to use adequate contraception during this study and for 60 days after discontinuation of study medication.
6. A concurrent infection, including diagnoses of FUO and evidence of possible central line sepsis (subjects must be afebrile at the start of therapy).
7. Any unstable oncologic emergency syndromes: superior vena cava syndrome, rising bilirubin needing stent placement, spinal cord compression, active bleeding, etc.
8. History of CNS metastasis, or other brain tumor, or history of stroke.
9. Radiation therapy within 6 weeks of Cycle 1 Week 1, or any radiation therapy which encompasses target lesions selected for this study unless those lesions have documented progression of disease.
10. Major surgery, open biopsy, or significant traumatic injury within 4 weeks of Cycle 1 Week 1, or anticipated need for major surgical procedure during the course of the study.
11. Fine needle aspiration or placement of a central line catheter within 7 days of Cycle 1 Week 1.
12. Inadequate bone marrow, liver or kidney function defined as:

    * Serum creatinine more than 1.5 times the upper limit of normal,
    * Urine protein to creatinine ratio \>1,
    * Serum bilirubin \> 2 times the upper limit of normal,
    * ANC \< 1.5 x 109/L,
    * Hemoglobin \< 9.0 g / dL
    * Platelet count \< 90 x 109/L,
    * SGOT (AST) and SGPT (ALT) more than 3 times the upper limit of normal, or more than 5 times the upper limit of normal for subjects with documented liver metastases.
13. Myocardial infarction, transient ischemic attack, cerebral bleeding, translumenal cardiac angiography or cardiac stent placement or other arterial thrombotic event within 12 months prior to Cycle 1 Week 1.
14. Active, clinically significant cardiovascular or symptomatic arterial peripheral vascular disease \[e.g., uncontrolled hypertension, congestive heart failure, claudication, unstable angina, symptomatic cardiac arrhythmia, or New York Heart Association (NYHA) Class 2 or greater\].
15. Presence of serious non-healing wounds, gastro-duodenal ulcers active by endoscopy, gastro-intestinal perforation or intra-abdominal abscess, skin ulcers, or bone fractures.
16. INR \>1.5 unless on therapeutic doses of oral anticoagulants (e.g. warfarin). If so, must have an in-range INR (usually between 2-3) on a stable dose of drug.
17. Participation in another experimental drug study within 4 weeks prior to Cycle 1 Week 1.
18. Known or suspected anaphylaxis reaction to leucovorin or any allergic reaction to a drug which, in the opinion of the Investigator, suggests an increased potential for a hypersensitivity to CoFactor or other study drug including excipients.
19. Presence of organ allograft requiring immunosuppressive therapy.
20. Unwilling or unable to comply with the study protocol or history of psychiatric disability judged by the investigator to preclude granting of informed consent.

Primary outcomes:
measure: Progression Free Survival
Secondary outcomes:
measure: Response Rate
measure: Overall Survival
measure: Incidence and Severity of Adverse Events
Other outcomes:
Locations:
city: Florence
country: United States
facility: Research Center In
state: Alabama
city: Anaheim
country: United States
facility: Research Center In
state: California
city: Apple Valley
country: United States
facility: Research Center In
state: California
city: Beverly Hills
country: United States
facility: Research Center In
state: California
city: Irvine
country: United States
facility: Research Center In
state: California
city: Mission Hills
country: United States
facility: Research Center In
state: California
city: Poway
country: United States
facility: Research Center In
state: California
city: Rancho Mirage
country: United States
facility: Research Center In
state: California
city: Sacramento
country: United States
facility: Mercy General Hospital
state: California
city: Sacramento
country: United States
facility: Research Center In
state: California
city: San Diego
country: United States
facility: Research Center In
state: California
city: San Diego
country: United States
facility: Research Site In
state: California
city: Vista
country: United States
facility: Research Center In
state: California
city: Boynton Beach
country: United States
facility: Research Center In
state: Florida
city: Merritt Island
country: United States
facility: Research Center In
state: Florida
city: Port St. Lucie
country: United States
facility: Research Center In
state: Florida
city: Tarpon Springs
country: United States
facility: Research Center In
state: Florida
city: Gurnee
country: United States
facility: Research Center In
state: Illinois
city: Joliet
country: United States
facility: Research Center In
state: Illinois
city: Skokie
country: United States
facility: Research Center In
state: Illinois
city: Indianapolis
country: United States
facility: Research Center In
state: Indiana
city: Wichita
country: United States
facility: Research Center In
state: Kansas
city: Hazard
country: United States
facility: Research Center In
state: Kentucky
city: Baltimore
country: United States
facility: Research Center In
state: Maryland
city: Flint
country: United States
facility: Research Center In
state: Michigan
city: Freesoil
country: United States
facility: Research Center In
state: Michigan
city: Grand Rapids
country: United States
facility: Research Center In
state: Michigan
city: Port Huron
country: United States
facility: Research Center In
state: Michigan
city: Jackson
country: United States
facility: Research Center In
state: Mississippi
city: Henderson
country: United States
facility: Research Center In
state: Nevada
city: Las Vegas
country: United States
facility: Research Center In
state: Nevada
city: Reno
country: United States
facility: Research Center In
state: Nevada
city: Cherry Hill
country: United States
facility: Research Center In
state: New Jersey
city: Farmington
country: United States
facility: Research Center In
state: New Mexico
city: East Setauket
country: United States
facility: Research Center In
state: New York
city: Greenville
country: United States
facility: Research Center In
state: North Carolina
city: Middletown
country: United States
facility: Research Center In
state: Ohio
city: Cranston
country: United States
facility: Research Center In
state: Rhode Island
city: Charleston
country: United States
facility: Research Center In
state: South Carolina
city: Columbia
country: United States
facility: Research Center In
state: South Carolina
city: Chattanooga
country: United States
facility: Research Center In
state: Tennessee
city: Collierville
country: United States
facility: Research Center In
state: Tennessee
city: Fort Worth
country: United States
facility: Research Center In
state: Texas
city: Ogden
country: United States
facility: Research Center In
state: Utah
city: Lacey
country: United States
facility: Research Center In
state: Washington
city: Walla Walla
country: United States
facility: Research Center In
state: Washington
city: Zrenjanin
country: Former Serbia and Montenegro
facility: Research Center In
Study officials:
affiliation: Yale University
name: M. Wasif Saif, MD, MBBS
role: STUDY_CHAIR
References: