Study of the Anti-Angiogenesis Agent Axitinib in Patients With Stage III Malignant Melanoma - Full Text View

Purpose

The purpose of this research study is to determine the efficacy of Axitinib in treating individuals with Stage III melanoma.

Condition	Intervention	Phase
Melanoma Malignant Melanoma	Drug: Axitinib	Phase 2

Study Type:	Interventional
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Melanoma

Drug Information available for: Axitinib

U.S. FDA Resources

Further study details as provided by University of California, Irvine:

Primary Outcome Measures:

To determine progression-free survival (PFS) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
The primary objective of this study is to determine the activity of AG-013736 in metastatic melanoma as measured by the overall response rate, complete response (CR) and partial response (PR) by RECIST. A response will also be considered to have occurred if there is a >/= 30% reduction in the involved nodal basin specific uptake value (SUV) on PET/CT.

Secondary Outcome Measures:

Determine the response rate according to RECIST criteria, safety profile of AG-013736, duration of response, and overall survival. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
The secondary objectives include the following:
- determine the safety profile of AG-013736
- determine the progression-free survival
- determine overall survival
- obtain blood samples for population pharmacokinetic analyses
- explore relationships between clinical response and plasma soluble proteins
- explore relationships between clinical response with host and tumor genomics

Estimated Enrollment:	60
Study Start Date:	December 2011
Estimated Study Completion Date:	December 2017
Estimated Primary Completion Date:	December 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Axitinib Axitinib will be administered 5 mg orally twice each day (BID) continuously. Dose adjustments will be based on adverse events. Eighteen patients will be entered into the first stage of a 2-stage Simon Minimax design. If there is ≥ 1 response, 14 additional patients will be entered. Up to 28 additional patients (for a total of up to 60) may be treated in order to gain additional safety and activity information should the initial 2-stage trial be positive at the end of Stage 2. Multiple centers will be used to accrue patients in a 12-month period.	Drug: Axitinib Axitinib will be administered 5 mg orally twice each day (BID) continuously. Dose adjustments will be based on adverse events. Eighteen patients will be entered into the first stage of a 2-stage Simon Minimax design. If there is ≥ 1 response, 14 additional patients will be entered. Up to 28 additional patients (for a total of up to 60) may be treated in order to gain additional safety and activity information should the initial 2-stage trial be positive at the end of Stage 2. Multiple centers will be used to accrue patients in a 12-month period. Other Name: AG-013736

Arms

Assigned Interventions

Experimental: Axitinib

Axitinib will be administered 5 mg orally twice each day (BID) continuously. Dose adjustments will be based on adverse events.

Eighteen patients will be entered into the first stage of a 2-stage Simon Minimax design. If there is ≥ 1 response, 14 additional patients will be entered. Up to 28 additional patients (for a total of up to 60) may be treated in order to gain additional safety and activity information should the initial 2-stage trial be positive at the end of Stage 2. Multiple centers will be used to accrue patients in a 12-month period.

Drug: Axitinib

Axitinib will be administered 5 mg orally twice each day (BID) continuously. Dose adjustments will be based on adverse events.

Eighteen patients will be entered into the first stage of a 2-stage Simon Minimax design. If there is ≥ 1 response, 14 additional patients will be entered. Up to 28 additional patients (for a total of up to 60) may be treated in order to gain additional safety and activity information should the initial 2-stage trial be positive at the end of Stage 2. Multiple centers will be used to accrue patients in a 12-month period.

Other Name: AG-013736

Detailed Description:

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. However, because large-scale clinical trials are often necessary to demonstrate the safety and effectiveness of a drug, it is desirable to determine if new agents provide some measure of effectiveness of these new agents prior to investing in such studies.

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. Besides having the potential to block the growth of blood vessels (angiogenesis) through VEGFR TK inhibition, Axitinib also has the additional antitumor potential through platelet derived growth factor receptor (PDGFR) TK inhibition.

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 to determine its activity and tolerability for Stage III melanoma. As a Phase 2 open label study of Axitinib, each consented patient who meets all inclusion criteria will initially receive 5 mg orally twice daily. Study tests, procedures and monitoring will be performed throughout the study to determine therapy response rate and patient safety.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

18 years of age or older.
Confirmed diagnosis of Stage III Melanoma, with lymph node involvement.
Agreement to use an effective contraceptive method, continuing until 1 year after last dose of Axitinib.
Adequate organ function, bone marrow, liver, and kidney, as confirmed by blood and urine laboratory tests.
Willingness to sign and give written informed consent for participation in the study.

Exclusion Criteria:

Have a diagnosis of Stage IV melanoma
Have any of the following gastrointestinal abnormalities including:
1. inability to take oral medication
2. need to receive nourishment intravenously (through an IV inserted into your blood vessel)
3. prior surgical procedures affecting absorption including gastric resection
4. treatment for active peptic ulcer disease in the past 6 months
5. active gastrointestinal bleeding, unrelated to cancer in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy.
6. malabsorption syndromes.
Have an active seizure disorder or evidence of brain metastases.
Have a serious uncontrolled medical disorder or active infection that would impair ability to receive study treatment.
Have a history of a malignancy (other than melanoma) except those treated with curative intent for skin cancer (other than melanoma) or in situ breast or cervical cancer or those treated with curative intent for any other cancer with no evidence of disease for 5 years
Have had major surgery or any radiation therapy within 4 weeks of treatment.
Men with child fathering potential who are not using adequate contraception or practicing abstinence
Women of childbearing potential who are not using adequate contraception or practicing abstinence.
Women who are pregnant or breast-feeding.

Please note this is not a complete list of eligibility criteria.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01321437

Contacts

Contact: Chao Family Comprehensive Cancer Center University of California, Irvine Medical Center

1-877-UC-STUDY

ucstudy@uci.edu

Locations

United States, California
Chao Family Comprehensive Cancer Center	Recruiting
Orange, California, United States, 92868
Principal Investigator: John P. Fruehauf, MD, PhD

Sponsors and Collaborators

University of California, Irvine

Pfizer

Investigators

Principal Investigator:

John P. Fruehauf, MD, PhD

Chao Family Comprehensive Cancer Center

More Information

No publications provided

Responsible Party:	Chao Family Comprehensive Cancer Center, Cancer Center, University of California, Irvine
ClinicalTrials.gov Identifier:	NCT01321437 History of Changes
Other Study ID Numbers:	UCI 10-55, 2011-8282
Study First Received:	March 21, 2011
Last Updated:	October 26, 2012
Health Authority:	United States: Food and Drug Administration United States: Institutional Review Board

Keywords provided by University of California, Irvine:

Melanoma
Axitinib
Anti-angiogenesis
Neoadjuvant Melanoma

Additional relevant MeSH terms:

Melanoma
Nevi and Melanomas
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue

Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on June 17, 2013