Study of the Anti-Angiogenesis Agent Axitinib in Patients With Stage III Malignant Melanoma
Stage IIIA Melanoma
Stage IIIB Melanoma
Stage IIIC Melanoma
Procedure: therapeutic conventional surgery
Other: laboratory biomarker analysis
Other: pharmacological study
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase 2 Study of the Anti-Angiogenesis Agent Axitinib (AG-013736) in Patients With Stage III Malignant Melanoma|
- Overall response rate, defined as the percentage of patients with a confirmed Clinical Response (CR) or Partial Response (PR) [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]The response rate (CR or PR according to Response Evaluation Criteria in Solid Tumors (RECIST) will be provided with an exact 95% 2-sided confidence interval calculated using a method based on the F distribution.
- Progression-free survival (PFS) [ Time Frame: From the date of first dose of axitinib to the first date that criteria for progression were met or the patient died, assessed up to 1 year ] [ Designated as safety issue: No ]An estimate of the PFS curve from the Kaplan-Meier method will be presented. Median event time and a 2-sided 95% confidence interval for the median will be provided.
- Duration of overall response [ Time Frame: From the day the criteria for PR or CR were met to the first day criteria for progression occurred, assessed up to 1 year ] [ Designated as safety issue: No ]Estimates of duration of overall response from the Kaplan-Meier method will be presented. Median event time (if appropriate) and a 2-sided 95% confidence interval for the median will be provided. The number of CR and PR patients may be small and thereby limit use of the Kaplan-Meier method to provide reliable information. In this case, descriptive statistics or listings will be provided.
- Survival [ Time Frame: From the day of first dose of axitinib to the day of death, assessed up to 1 year ] [ Designated as safety issue: No ]An estimate of the survival time curve from the Kaplan-Meier method will be presented. Median event time and a 2-sided 95% confidence interval for the median will be provided.
- Frequencies of patients experiencing at least one adverse event (AE) [ Time Frame: Up to at least 28 days after the last dose of study drug ] [ Designated as safety issue: Yes ]Will be displayed by body system and preferred term according to Medical Dictionary for Regulatory Activities (MedDRA) terminology. Detailed information collected for each AE will include: description of the event, duration, whether the AE was serious, intensity, relationship to study drug, action taken, and clinical outcome. Intensity (severity) of the AEs will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
|Study Start Date:||December 2011|
|Estimated Study Completion Date:||December 2019|
|Estimated Primary Completion Date:||December 2018 (Final data collection date for primary outcome measure)|
Patients receive axitinib PO BID on days 1-28. Treatment repeats every 4 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery within 14-21 days after completion of treatment. Beginning 28-56 days after surgery, patients receive axitinib PO BID on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity
Procedure: therapeutic conventional surgery
Undergo surgeryOther: laboratory biomarker analysis
Correlative studiesDrug: Axitinib
Axitinib will be administered 5 mg orally twice each day (BID) continuously. Dose adjustments will be based on adverse events.
Other Names:Other: pharmacological study
The American Cancer Society estimates that there will be about 68,720 new cases of melanoma (29,900 in men and 25,200 in women) annually in the United States, and about 8,650 people will die from this cancer. The systemic therapy of advanced disease remains palliative until new agents are found that might improve the survival of patients with stage III melanoma.
Melanomas are often vascular, and a decrease in the number of blood vessels that supply the tumor may starve it of needed nutrients. An approach to blocking the growth of blood vessels that supply the tumor is to inhibit the vascular endothelial growth factor receptor tyrosine kinase (VEGFR TK) signaling pathway. Axitinib (AG 013736) is a VEGFR TK inhibitor.
Because of the poor prognosis of patients with stage III melanoma and indications that anti-angiogenesis compounds might have clinically meaningful activity in this disease, a Phase 2 trial of the vascular endothelial growth factor receptor tyrosine kinase (VEGFR TK) inhibitor Axitinib (AG 013736) is warranted.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01321437
|United States, California|
|Chao Family Comprehensive Cancer Center|
|Orange, California, United States, 92868|
|Principal Investigator:||John P. Fruehauf, MD, PhD||Chao Family Comprehensive Cancer Center|