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

Rectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00337389
• Other study ID #: 510-05
• Status: Active, not recruiting
• Phase: Phase 3
• First received: June 14, 2006
• Last updated: November 15, 2007
• Start date: May 2006

Study information

• Verified date: November 2007
• Source: Mast Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1200
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colon Cancer
• Colorectal Neoplasms
• Metastatic Colorectal Cancer
• Rectal Cancer

Intervention

Drug:
• 5- Fluorouracil (5-FU)

• bevacizumab (Avastin)

• Leucovorin

• CoFactor (ANX-510)

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Mast Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Former Serbia and Montenegro, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival
Secondary	Response Rate
Secondary	Overall Survival
Secondary	Incidence and Severity of Adverse Events