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

An Open-Label, Multicenter, Phase II Trial of ABI-007 (A Cremophor® -Free, Protein Stabilized, Nanoparticle Paclitaxel) in Previously Treated Patients With Metastatic Melanoma

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.

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.

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