Patient case: 55-year-old male with Melanoma. Genetic variant: NRAS (Q61K). Other conditions: Hypertension.

Clinical trial: ABI-007 in Treating Patients With Inoperable Locally Recurrent or Metastatic Melanoma

Summary: RATIONALE: Drugs used in chemotherapy, such as ABI-007, work in different ways to stop tumor cells from dividing so they stop growing or die.
  PURPOSE: This phase II trial is studying how well ABI-007 works in treating patients with inoperable (unresectable) locally recurrent or metastatic melanoma.

Detailed description: OBJECTIVES:
  Primary
  -  Determine the antitumor activity of ABI-007 in patients with inoperable locally recurrent or metastatic melanoma.
  -  Determine the safety and tolerability of this drug in these patients.
  Secondary
  -  Determine the time to disease progression, in terms of the rate and duration of response or stable disease, in patients treated with this drug.
  -  Determine the survival of patients treated with this drug.
  -  Determine the effects of this drug on biomarkers of melanoma in these patients.
  -  Correlate biomarker levels with response in patients treated with this drug.
  OUTLINE: This is an open-label, multicenter study. Patients are assigned to 1 of 2 treatment cohorts according to prior cytotoxic chemotherapy (previously treated vs chemotherapy-naïve).
  -  Cohort I (previously treated): Patients receive ABI-007 IV over 30 minutes on days 1, 8, and 15.
  -  Cohort II (chemotherapy-naïve): Patients receive a higher dose of ABI-007 as in cohort I.
  In both cohorts, courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
  Patients are followed monthly for 6 months and then every 3 months thereafter.
  PROJECTED ACCRUAL: A total of 24-70 patients (12-35 per cohort) will be accrued for this study.

Eligibility: DISEASE CHARACTERISTICS:
  -  Histologically or cytologically confirmed melanoma
  -  Inoperable locally recurrent or metastatic disease
  -  Measurable disease
  -  No lytic or blastic bone metastasis as only evidence of metastasis
  -  Prior radiotherapy to a target lesion allowed provided there has been clear progression of disease since completion of radiotherapy
  -  No active brain metastasis, including leptomeningeal involvement
  -  Prior brain metastasis allowed provided the disease is in complete remission for at least 1 month after therapy
  PATIENT CHARACTERISTICS:
  Age
  -  18 and over
  Performance status
  -  ECOG 0-1
  Life expectancy
  -  More than 12 weeks
  Hematopoietic
  -  Absolute neutrophil count ≥ 1,500/mm^3
  -  Platelet count ≥ 100,000/mm^3
  -  Hemoglobin ≥ 9 g/dL
  Hepatic
  -  AST and ALT ≤ 2.5 times upper limit of normal (ULN)
  -  Alkaline phosphatase ≤ 2.5 times ULN (unless bone metastasis is present in the absence of liver metastasis)
  -  Bilirubin ≤ 1.5 mg/dL
  Renal
  -  Creatinine ≤ 1.5 mg/dL
  Other
  -  Not pregnant or nursing
  -  Negative pregnancy test
  -  Fertile patients must use effective barrier contraception 1 month before and during study participation
  -  No pre-existing peripheral neuropathy ≥ grade 2
  -  No prior allergy or hypersensitivity to study drug
  -  No concurrent clinically significant illness
  -  No other concurrent active malignancy
  -  No serious medical risk factors involving any of the major organ systems that would preclude study participation
  PRIOR CONCURRENT THERAPY:
  Biologic therapy
  -  Not specified
  Chemotherapy
  -  Recovered from prior chemotherapy
  -  More than 4 weeks since prior cytotoxic chemotherapy
  -  At least 3 weeks since prior anthracyclines
  -  No concurrent taxane or anthracyclines
  -  No concurrent doxorubicin
  Endocrine therapy
  -  No concurrent steroids except as needed for hypersensitivity to study drug
  Radiotherapy
  -  See Disease Characteristics
  -  Concurrent radiotherapy to a symptomatic non-target lesion (including recurrent or new brain metastases that develop during study participation) allowed
  Surgery
  -  Not specified
  Other
  -  More than 4 weeks since prior investigational drugs and recovered
  -  No other concurrent anticancer therapy
  -  No concurrent participation in another clinical study
  -  No other concurrent investigational therapies
  -  No concurrent ritonavir, saquinavir, indinavir, or nelfinavir

Relevance to patient case: not relevant