A Trial of Single Agent Axitinib as Maintenance Therapy for Patients With First Line Metastatic Colorectal Cancer (mCRC)
Condition: Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: Axitinib; Bevacizumab; 5-Fluorouracil; 5-Fluorouracil; Leucovorin; Oxaliplatin
Intervention description: 5-mg tablets PO BID; 5 mg/kg Days 1 and 15; IV; 400 mg/m2 Days 1 and 15; IV; 2400 mg/m2 over 46-48 hours Days 1 and 15; Continuous Intravenous; 400 mg/m2 Days 1 and 15; IV; 85 mg/m2 Days 1 and 15; IV
Intervention MeSH terms: Leucovorin; Bevacizumab; Fluorouracil; Oxaliplatin; Axitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 70.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Colorectal Cancer; Axitinib; FOLFOX/Bevacizumab

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.
    

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.