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

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

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.

• Melanoma
• Malignant Melanoma

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.