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.
- 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.
- 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
- 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
In both cohorts, courses repeat every 4 weeks in the absence of disease progression or
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
- 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
- 18 and over
- ECOG 0-1
- More than 12 weeks
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Hemoglobin ≥ 9 g/dL
- 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
- Creatinine ≤ 1.5 mg/dL
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective barrier contraception 1 month before and during
- 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:
- Not specified
- 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
- No concurrent steroids except as needed for hypersensitivity to study drug
- See Disease Characteristics
- Concurrent radiotherapy to a symptomatic non-target lesion (including recurrent or
new brain metastases that develop during study participation) allowed
- Not specified
- 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