a trial of single agent axitinib as maintenance therapy for patients with first line metastatic colorectal cancer (mcrc)

Conditions: Colorectal Cancer

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.

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 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.

Keywords: colorectal cancer axitinib folfox/bevacizumab