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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier:
NCT01490866
First received: November 7, 2011
Last updated: January 22, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer
Drug: Axitinib
Drug: Bevacizumab
Drug: 5-FU
Drug: Leucovorin
Drug: Oxaliplatin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Single Agent Axitinib as Maintenance Therapy for Patients With First Line Metastatic Colorectal Cancer (mCRC)

Resource links provided by NLM:


Further study details as provided by SCRI Development Innovations, LLC:

Primary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Determine the PFS of patients with first-line mCRC treated with maintenance axitinib after initial treatment with FOLFOX plus bevacizumab.


Secondary Outcome Measures:
  • Objective Response Rate (ORR) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Determine the Response Rate of patients with first-line mCRC treated with maintenance axitinib after initial treatment with FOLFOX plus bevacizumab.

  • Toxicities [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
    Abnormal Thyroid Function - Serum or plasma thyroid function tests; Gastrointestinal Disorders - Supportive care for these events may include pre-medication with anti-emetics; Hematological and Urinary Disorders - Urine dipstick test; Hypertension - Measurements of BP

  • Time To Progression (TTP) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Determine Time To Progression of patients with first-line mCRC treated with maintenance axitinib after initial treatment with FOLFOX plus bevacizumab.

  • Overall Survival (OS) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Determine Overall Survival (OS) of patients with first-line mCRC treated with maintenance axitinib after initial treatment with FOLFOX plus bevacizumab.


Enrollment: 69
Study Start Date: December 2011
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: axitinib/bevacizumab Treatment

Phase II trial investigating axitinib as a single-agent maintenance therapy following standard first-line FOLFOX/bevacizumab therapy for patients with mCRC.

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

Drug: Axitinib
5-mg tablets PO BID
Drug: Bevacizumab
5 mg/kg Days 1 and 15; IV
Drug: 5-FU
400 mg/m2 Days 1 and 15; IV
Other Name: Fluorouracil
Drug: 5-FU
2400 mg/m2 over 46-48 hours Days 1 and 15; Continuous Intravenous
Other Name: Fluorouracil
Drug: Leucovorin
400 mg/m2 Days 1 and 15; IV
Drug: Oxaliplatin
85 mg/m2 Days 1 and 15; IV

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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  • Male or female patients >=18 years-of-age.
  • Life expectancy >=12 weeks.
  • Adequate hematologic function defined as:

    • Absolute neutrophil count (ANC) >=1500/μL
    • Hemoglobin (Hgb) >=9 g/dL (5.6 mmol/L).
    • Platelets >=100,000/uL
  • Adequate liver function defined as:

    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <2.5 x the institutional upper limit of normal (ULN) or <=5.0 x the institutional ULN in patients with liver metastases.
    • Total bilirubin within normal limits (WNL) (or <=1.5 x the institutional ULN in patients with liver metastases; or total bilirubin <=3.0 x ULN with direct bilirubin within normal limits in patients with well documented Gilbert Syndrome).
  • Adequate renal function defined as: serum creatinine <=1.5 mg/dL OR calculated 24 hour creatinine clearance >=60 mL/min.
  • 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.
  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: NCT01490866

Locations
United States, Arkansas
NEA Baptist Clinic
Jonesboro, Arkansas, United States, 72401
United States, Florida
Florida Cancer Specialists-South
Fort Myers, Florida, United States, 33916
Woodlands Medical Specialists
Pensacola, Florida, United States, 32503
Florida Cancer Specialists-North
St. Petersburg, Florida, United States, 33705
United States, Georgia
Northeast Georgia Medical Center
Gainesville, Georgia, United States, 30501
United States, Indiana
Oncology Hematology of SW Indiana
Newburgh, Indiana, United States, 47630
Hope Cancer Center
Terre Haute, Indiana, United States, 47802
United States, Michigan
Grand Rapids Oncology Program
Grand Rapids, Michigan, United States, 49503
United States, Nebraska
Nebraska Methodist Hospital
Omaha, Nebraska, United States, 68114
United States, New Jersey
Atlantic Health System
Summit, New Jersey, United States, 07901
United States, Tennessee
Tennessee Oncology
Nashville, Tennessee, United States, 37203
United States, Texas
Texas Health Physician Group
Dallas, Texas, United States, 75243
Sponsors and Collaborators
SCRI Development Innovations, LLC
Pfizer
Investigators
Study Chair: Johanna Bendell, M.D. SCRI Development Innovations, LLC
  More Information

No publications provided

Responsible Party: SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier: NCT01490866     History of Changes
Other Study ID Numbers: SCRI GI 154
Study First Received: November 7, 2011
Last Updated: January 22, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by SCRI Development Innovations, LLC:
Colorectal Cancer
Axitinib
FOLFOX/Bevacizumab

Additional relevant MeSH terms:
Colorectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Axitinib
Bevacizumab
Fluorouracil
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014