Study of the Anti-Angiogenesis Agent Axitinib in Patients With Stage III Malignant Melanoma
Condition: Melanoma; Malignant Melanoma; Stage IIIA Melanoma; Stage IIIB Melanoma; Stage IIIC Melanoma
MeSH terms: Melanoma
Intervention: therapeutic conventional surgery; laboratory biomarker analysis; Axitinib; pharmacological study
Intervention description: Undergo surgery; Correlative studies; Axitinib will be administered 5 mg orally twice each day (BID) continuously. Dose adjustments will be based on adverse events.; Correlative studies
Intervention MeSH terms: Axitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Melanoma; Axitinib; Anti-angiogenesis; Neoadjuvant Melanoma

Summary:

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

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically documented melanoma with local lymph node stage III metastases.

          -  No prior systemic therapy. Prior adjuvant therapy with interferon does not count.

          -  No expectation of further effects of prior anticancer therapy.

          -  At least 1 target lesion, as defined by RECIST, that has not been irradiated. New
             lesions that have developed in a previously irradiated field may be used as sites of
             measurable disease assuming all other criteria are met. All target lesions must have a
             unidimensional diameter of at least 1 cm for spiral CT scans if the reconstruction
             algorithm is 0.5 cm), or an standard uptake value (SUV) value ≥ 2.5. Baseline
             measurements/evaluations must be completed within 4 weeks prior to treatment.

          -  Adequate bone marrow, hepatic, and renal function documented within 14 days prior to
             treatment as documented by:

               -  absolute neutrophil count (ANC, calculated as the absolute number of neutrophils
                  and bands) ≥1.5 x 10^9 cells/L

               -  platelets ≥100 x 10^9 cells /L

               -  aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x upper
                  limit of normal (ULN), unless there are liver metastases in which case AST and
                  ALT ≤5.0 x ULN

               -  total bilirubin ≤1.5 x ULN

               -  serum creatinine ≤1.5 x ULN or calculated creatinine clearance ≥60 mL/min

               -  urinary protein <2+ by urine dipstick. If dipstick is ≥2+ then a 24-hour urine
                  collection can be done and the patient may enter only if urinary protein is <2 g
                  per 24 hours

          -  Age ≥18 years.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  No evidence of preexisting uncontrolled hypertension as documented by 2 baseline blood
             pressure readings taken at least 1 hour apart. The baseline systolic blood pressure
             readings must be ≤140, and the baseline diastolic blood pressure readings must be ≤90.
             Patients whose hypertension is controlled by antihypertensive therapies are eligible.

          -  Women of childbearing potential must have a negative serum or urine pregnancy test
             within 7 days prior to treatment.

          -  Written and voluntary informed consent

        Exclusion Criteria:

          -  Stage IV disease

          -  History of hemoptysis

          -  Gastrointestinal abnormalities including:

               -  inability to take oral medication

               -  requirement for intravenous alimentation

               -  prior surgical procedures affecting absorption including gastric resection

               -  treatment for active peptic ulcer disease in the past 6 months

               -  active gastrointestinal bleeding, unrelated to cancer, as evidenced by
                  hematemesis, hematochezia or melena in the past 3 months without evidence of
                  resolution documented by endoscopy or colonoscopy.

               -  malabsorption syndromes.

          -  Previous treatment with anti-angiogenesis agents including thalidomide, or inhibitors
             of epidermoid growth factor (EGF), platelet derived growth factor (PDGF), or
             fibroblast growth factors (FGF) receptors.

          -  Current use or anticipated inability to avoid use of drugs that are known potent
             cytochrome P450 3A4 (CYP3A4) inhibitors (ie, grapefruit juice, verapamil,
             ketoconazole, miconazole, itraconazole, erythromycin, clarithromycin, ergot
             derivatives, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, and
             delavirdine).

          -  Current use or anticipated inability to avoid use of drugs that are known CYP3A4 or
             Cytochrome P450 1A2 (CYP1A2) inducers (ie, carbamazepine, dexamethasone, felbamate,
             omeprazole, phenobarbital, phenytoin, primidone, rifabutin, rifampin, and St. John's
             wort).

          -  Active seizure disorder or evidence of brain metastases. (Appropriate imaging should
             be done to rule out brain metastases.)

          -  A serious uncontrolled medical disorder or active infection that would impair their
             ability to receive study treatment.

          -  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.

          -  10. Major surgical procedure or any radiation therapy within 4 weeks of treatment,
             minimum rest period is 28 days post surgery; maximum rest period 56 days post surgery.

          -  Dementia or significantly altered mental status that would prohibit the understanding
             or rendering of informed consent and compliance with the requirements of this
             protocol.

          -  Patients (male and female) having procreative potential who are not using adequate
             contraception or practicing abstinence.

          -  Women who are pregnant or breast-feeding.