A Trial of Single Agent Axitinib as Maintenance Therapy for Patients With First Line Metastatic Colorectal Cancer (mCRC)

NCT ID: NCT01490866

Last Updated: 2019-09-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-31
• Study Completion Date: 2015-07-31

Brief Summary

This is a non-randomized, open-label, Phase II trial investigating axitinib as a single-agent maintenance therapy following standard first-line FOLFOX/bevacizumab therapy for patients with mCRC.

Detailed Description

All patients will receive FOLFOX/bevacizumab for four 28-day cycles (a total of 16 weeks). After 4 cycles, maintenance axitinib will be started. With approval of the Medical Monitor,patients who are having significant benefit from FOLFOX/bevacizumab may continue chemotherapy to a maximum of six 28-day cycles. During trial treatment, all patients will be assessed for response every 8 weeks (2 cycles).

Conditions

Colorectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

FOLFOX/bevacizumab and Axitinib

Phase II trial investigating axitinib as a single-agent maintenance therapy following standard first-line FOLFOX/bevacizumab therapy for patients with mCRC. (FOLFOX is a combination of 5-Fluorouracil, Leucovorin and Oxaliplatin.)

All patients will receive FOLFOX/bevacizumab for four 28-day cycles (a total of 16 weeks). After 4 cycles, maintenance axitinib will be started.

Group Type: EXPERIMENTAL

Axitinib

Intervention Type: DRUG

5-mg tablets PO BID

Bevacizumab

Intervention Type: DRUG

5 mg/kg Days 1 and 15; IV

5-Fluorouracil

Intervention Type: DRUG

400 mg/m2 Days 1 and 15; IV

5-Fluorouracil

Intervention Type: DRUG

2400 mg/m2 over 46-48 hours Days 1 and 15; Continuous Intravenous

Leucovorin

Intervention Type: DRUG

400 mg/m2 Days 1 and 15; IV

Oxaliplatin

Intervention Type: DRUG

85 mg/m2 Days 1 and 15; IV

Interventions

Axitinib

5-mg tablets PO BID

Intervention Type: DRUG

Bevacizumab

5 mg/kg Days 1 and 15; IV

Intervention Type: DRUG

5-Fluorouracil

400 mg/m2 Days 1 and 15; IV

Intervention Type: DRUG

5-Fluorouracil

2400 mg/m2 over 46-48 hours Days 1 and 15; Continuous Intravenous

Intervention Type: DRUG

Leucovorin

400 mg/m2 Days 1 and 15; IV

Intervention Type: DRUG

Oxaliplatin

85 mg/m2 Days 1 and 15; IV

Intervention Type: DRUG

Other Intervention Names

AG-013736; Avastin; 5-FU; 5-FU; folinic acid; Eloxatin

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically confirmed metastatic adenocarcinoma of the colon or rectum.
• Patients must have measurable disease per RECIST Version 1.1.
• No previous systemic therapy for metastatic colorectal cancer. Previous radiosensitizing chemotherapy is allowed, if completed at least 4 weeks prior to Cycle 1 Day 1 of study treatment, and previous neoadjuvant and/or adjuvant chemotherapy is allowed, if completed at least 6 months prior to diagnosis of metastatic disease.
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 to 1.
• Life expectancy >=12 weeks.
• Adequate hematologic, renal and hepatic function
• Patients who are on coumadin should have an INR value within the therapeutic range (i.e., 2 to 3 x ULN). Patients who are on stable, chronic doses of coumadin are eligible.
• Male patients willing to use adequate contraceptive measures. Female patients who are not of child-bearing potential, and female patients of child-bearing potential who agree to use adequate contraceptive measures, who are not breastfeeding, and who have a negative serum or urine pregnancy test performed within 72 hours prior to start of treatment.
• Willingness and ability to comply with the trial and follow-up procedures.
• Ability to understand the investigative nature of this trial and give written informed consent.

Exclusion Criteria

• History or known presence of central nervous system (CNS) metastases.
• Patients who have had a major surgical procedure (not including mediastinoscopy), or significant traumatic injury <=4 weeks prior to beginning treatment.
• Women who are pregnant or lactating. All females of child-bearing potential must have negative serum or urine pregnancy tests within 72 hours prior to study treatment (see Appendix D)
• History of hypersensitivity to active or inactive excipients of any component of treatment (5 fluorouracil, bevacizumab, oxaliplatin, or axitinib), or known dipyrimidine dehydrogenase deficiency.
• Patients with proteinuria at screening as demonstrated by:

• Urine dipstick for proteinuria >=2+ (patients discovered to have >=2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection, and must demonstrate <=1 g of protein/24 hours to be eligible)
• Patients with a serious non healing wound, active ulcer, or untreated bone fracture.
• Patients with evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation).
• Patients with history of hematemesis or hemoptysis (defined as having bright red blood of ½ teaspoon or more per episode) <=1 month prior to study enrollment.
• Patients requiring concomitant treatment with potent CYP3A4 or CYP1A2 inducers and CYP3A4 inhibitors.
• History of myocardial infarction or unstable angina <=6 months prior to beginning treatment.
• Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg while on antihypertensive medications). Initiation of antihypertensive agents is permitted provided adequate control is documented at least 1 week prior to Day 1 of study treatment.
• New York Heart Association Grade II or greater congestive heart failure.
• Serious cardiac arrhythmia requiring medication. Patients with chronic, rate-controlled atrial fibrillation are eligible.
• Significant vascular disease (e.g., aortic aneurysm requiring surgical repair, or recent peripheral arterial thrombosis) <=6 months prior to Day 1 of treatment.
• History of stroke or transient ischemic attack <=6 months prior to beginning treatment.
• Any prior history of hypertensive crisis or hypertensive encephalopathy.
• History of abdominal fistula or gastrointestinal perforation <=6 months prior to Day 1 of beginning treatment.
• Concurrent severe, intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.
• Any known positive test for human immunodeficiency virus, hepatitis C virus or acute or chronic hepatitis B infection.
• Mental condition that would prevent patient comprehension of the nature of, and risk associated with, the study.
• Use of any non-approved or investigational agent <=28 days prior to administration of the first dose of study drug. Patients may not receive any other investigational or anti-cancer treatments while participating in this study.
• Past or current history of neoplasm other than the entry diagnosis with the exception of treated non-melanoma skin cancer or carcinoma in situ of the cervix, or other cancers cured by local therapy alone and a disease free survival >=5 years.
• Infection requiring IV antibiotics.
• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter drug absorption (e.g. active inflammatory bowel disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or significant small bowel resection).
• Inability to swallow whole tablets.
• Patients with > Grade 2 peripheral neuropathy.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

SCRI Development Innovations, LLC

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Johanna Bendell, M.D.

Role: STUDY_CHAIR

SCRI Development Innovations, LLC

Locations

NEA Baptist Clinic

Jonesboro, Arkansas, United States

Florida Cancer Specialists-South

Fort Myers, Florida, United States

Woodlands Medical Specialists

Pensacola, Florida, United States

Florida Cancer Specialists-North

St. Petersburg, Florida, United States

Northeast Georgia Medical Center

Gainesville, Georgia, United States

Oncology Hematology of SW Indiana

Newburgh, Indiana, United States

Hope Cancer Center

Terre Haute, Indiana, United States

Grand Rapids Oncology Program

Grand Rapids, Michigan, United States

Nebraska Methodist Hospital

Omaha, Nebraska, United States

Atlantic Health System

Summit, New Jersey, United States

Tennessee Oncology

Nashville, Tennessee, United States

Texas Health Physician Group

Dallas, Texas, United States

Countries

United States

Other Identifiers

SCRI GI 154

Identifier Type: -

Identifier Source: org_study_id