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

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01490866
• Other study ID #: SCRI GI 154
• Status: Completed
• Phase: Phase 2
• Start date: January 2012
• Est. completion date: July 2015

Study information

• Verified date: September 2019
• Source: SCRI Development Innovations, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: July 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

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

Locations

Country	Name	City	State
United States	Texas Health Physician Group	Dallas	Texas
United States	Florida Cancer Specialists-South	Fort Myers	Florida
United States	Northeast Georgia Medical Center	Gainesville	Georgia
United States	Grand Rapids Oncology Program	Grand Rapids	Michigan
United States	NEA Baptist Clinic	Jonesboro	Arkansas
United States	Tennessee Oncology	Nashville	Tennessee
United States	Oncology Hematology of SW Indiana	Newburgh	Indiana
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	Woodlands Medical Specialists	Pensacola	Florida
United States	Florida Cancer Specialists-North	Saint Petersburg	Florida
United States	Atlantic Health System	Summit	New Jersey
United States	Hope Cancer Center	Terre Haute	Indiana

Sponsors (2)

Lead Sponsor	Collaborator
SCRI Development Innovations, LLC	Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival	Defined as the time from first treatment until objective tumor progression or death from any cause, assessed according to Response Evaluation Criteria for Solid Tumors (RECIST) v1.1.	24 months
Secondary	Objective Response Rate	Defined as the percentage of evaluable patients showing a complete or partial response (CR or PR) per RECIST v1.1 criteria. CR = disappearance of all lesions. PR = at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Stable disease (SD) = neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest (nadir) sum LD since start of treatment.	every 8 weeks, assessed up to approximately 24 months
Secondary	Time To Progression (TTP)	Defined as the time after a disease is diagnosed (or treated) until worsening of the disease.	every 8 weeks, assessed approximately up to 24 months
Secondary	Overall Survival (OS)	Defined as the time from first treatment until death from any cause.	every 8 weeks until progression then every 3 months for up to 5 years.
Secondary	Frequency of Adverse Events as a Measure of Safety	The frequency of adverse events (AEs) was analyzed in 2 groups of patients, those receiving FOLFOX/bevacizumab (N=70), and patients who received axitinib maintenance (N = 48). AEs were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0.	Every 4 weeks plus 30 days during treatment and up to 5 years thereafter.