Phase III Randomized Study of 5-FU, CoFactor, and Avastin vs. 5-FU, LV and Avastin for First-Line Colorectal Cancer.

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

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.

Study Overview

• Status: Unknown
• Conditions: Metastatic Colorectal Cancer; Rectal Cancer; Colon Cancer
• Intervention / Treatment: Drug: Leucovorin; Drug: 5- Fluorouracil (5-FU); Drug: bevacizumab (Avastin); Drug: CoFactor (ANX-510)

• Study Type: Interventional
• Enrollment (Anticipated): 1200
• Phase: Phase 3

Contacts and Locations

Study Locations

• Former Serbia and Montenegro
  • Zrenjanin, Former Serbia and Montenegro
    • Research Center In
• United States
  • Alabama
    • Florence, Alabama, United States
      • Research Center In
  • California
    • Anaheim, California, United States
      • Research Center In
    • Apple Valley, California, United States
      • Research Center In
    • Beverly Hills, California, United States
      • Research Center In
    • Irvine, California, United States
      • Research Center In
    • Mission Hills, California, United States
      • Research Center In
    • Poway, California, United States
      • Research Center In
    • Rancho Mirage, California, United States
      • Research Center In
    • Sacramento, California, United States, 95819
      • Mercy General Hospital
    • Sacramento, California, United States
      • Research Center In
    • San Diego, California, United States
      • Research Center In
    • San Diego, California, United States
      • Research Site In
    • Vista, California, United States
      • Research Center In
  • Florida
    • Boynton Beach, Florida, United States
      • Research Center In
    • Merritt Island, Florida, United States
      • Research Center In
    • Port St. Lucie, Florida, United States
      • Research Center In
    • Tarpon Springs, Florida, United States
      • Research Center In
  • Illinois
    • Gurnee, Illinois, United States
      • Research Center In
    • Joliet, Illinois, United States
      • Research Center In
    • Skokie, Illinois, United States
      • Research Center In
  • Indiana
    • Indianapolis, Indiana, United States
      • Research Center In
  • Kansas
    • Wichita, Kansas, United States
      • Research Center In
  • Kentucky
    • Hazard, Kentucky, United States
      • Research Center In
  • Maryland
    • Baltimore, Maryland, United States
      • Research Center In
  • Michigan
    • Flint, Michigan, United States
      • Research Center In
    • Freesoil, Michigan, United States
      • Research Center In
    • Grand Rapids, Michigan, United States
      • Research Center In
    • Port Huron, Michigan, United States
      • Research Center In
  • Mississippi
    • Jackson, Mississippi, United States
      • Research Center In
  • Nevada
    • Henderson, Nevada, United States
      • Research Center In
    • Las Vegas, Nevada, United States
      • Research Center In
    • Reno, Nevada, United States
      • Research Center In
  • New Jersey
    • Cherry Hill, New Jersey, United States
      • Research Center In
  • New Mexico
    • Farmington, New Mexico, United States
      • Research Center In
  • New York
    • East Setauket, New York, United States
      • Research Center In
  • North Carolina
    • Greenville, North Carolina, United States
      • Research Center In
  • Ohio
    • Middletown, Ohio, United States
      • Research Center In
  • Rhode Island
    • Cranston, Rhode Island, United States
      • Research Center In
  • South Carolina
    • Charleston, South Carolina, United States
      • Research Center In
    • Columbia, South Carolina, United States
      • Research Center In
  • Tennessee
    • Chattanooga, Tennessee, United States
      • Research Center In
    • Collierville, Tennessee, United States
      • Research Center In
  • Texas
    • Fort Worth, Texas, United States
      • Research Center In
  • Utah
    • Ogden, Utah, United States
      • Research Center In
  • Washington
    • Lacey, Washington, United States
      • Research Center In
    • Walla Walla, Washington, United States
      • Research Center In

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 1; CoFactor, 5-FU, Avastin	Drug: 5- Fluorouracil (5-FU); Drug: bevacizumab (Avastin); Drug: CoFactor (ANX-510)
ACTIVE_COMPARATOR: 2; Leucovorin, 5-FU, Avastin	Drug: Leucovorin; Drug: 5- Fluorouracil (5-FU); Drug: bevacizumab (Avastin)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Progression Free Survival

Secondary Outcome Measures

Outcome Measure
Response Rate
Overall Survival
Incidence and Severity of Adverse Events

Collaborators and Investigators

• Sponsor: Mast Therapeutics, Inc.
• Investigators: Study Chair: M. Wasif Saif, MD, MBBS, Yale University

Study record dates

Study Major Dates

• Study Start: May 1, 2006

Study Registration Dates

• First Submitted: June 14, 2006
• First Submitted That Met QC Criteria: June 14, 2006
• First Posted (ESTIMATE): June 16, 2006

Study Record Updates

• Last Update Posted (ESTIMATE): November 19, 2007
• Last Update Submitted That Met QC Criteria: November 15, 2007
• Last Verified: November 1, 2007

More Information

Terms related to this study

• Keywords: Cancer; Metastatic; Colorectal; Stage IV; CoFactor
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Micronutrients; Vitamins; Antidotes; Vitamin B Complex; Fluorouracil; Bevacizumab; Leucovorin
• Other Study ID Numbers: 510-05