Dataset Information

A phase II study of cell cycle inhibitor UCN-01 in patients with metastatic melanoma: a California Cancer Consortium trial.

ABSTRACT:

Background

Genetic abnormalities in cell cycle control are common in malignant melanoma. UCN-01 (7-hydroxystaurosporine) is an investigational agent that exhibits antitumor activity by perturbing the cancer cell cycle. A patient with advanced melanoma experienced a partial response in a phase I trial of single agent UCN-01. We sought to determine the activity of UCN-01 against refractory metastatic melanoma in a phase II study. Patients and methods Patients with advanced melanoma received UCN-01 at 90 mg/m(2) over 3 h on cycle 1, reduced to 45 mg/m(2) over 3 h for subsequent cycles, every 21 days. Primary endpoint was tumor response. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). A two-stage (17 + 16), single arm phase II design was employed. A true response rate of ? 20% (i.e., at least one responder in the first stage, or at least four responders overall) was to be considered promising for further development of UCN-01 in this setting. Results Seventeen patients were accrued in the first stage. One patient was inevaluable for response. Four (24%) patients had stable disease, and 12 (71%) had disease progression. As there were no responders in the first stage, the study was closed to further accrual. Median PFS was 1.3 months (95% CI, 1.2-3.0) while median OS was 7.3 months (95% CI, 3.4-18.4). One-year and two year OS rates were 41% and 12%, respectively. A median of two cycles were delivered (range, 1-18). Grade 3 treatment-related toxicities include hyperglycemia (N = 2), fatigue (N = 1), and diarrhea (N = 1). One patient experienced grade 4 creatinine elevation and grade 4 anemia possibly due to UCN-01. No dose modification was required as these patients had disease progression. Conclusion Although well tolerated, UCN-01 as a single agent did not have sufficient clinical activity to warrant further study in refractory melanoma.

SUBMITTER: Li T

PROVIDER: S-EPMC3277821 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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A phase II study of cell cycle inhibitor UCN-01 in patients with metastatic melanoma: a California Cancer Consortium trial.

Li Tianhong T Christensen Scott D SD Frankel Paul H PH Margolin Kim A KA Agarwala Sanjiv S SS Luu Thehang T Mack Philip C PC Lara Primo N PN Gandara David R DR

Investigational new drugs 20101022 2

<h4>Background</h4>Genetic abnormalities in cell cycle control are common in malignant melanoma. UCN-01 (7-hydroxystaurosporine) is an investigational agent that exhibits antitumor activity by perturbing the cancer cell cycle. A patient with advanced melanoma experienced a partial response in a phase I trial of single agent UCN-01. We sought to determine the activity of UCN-01 against refractory metastatic melanoma in a phase II study. Patients and methods Patients with advanced melanoma receive ...[more]

PMID: 20967484

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Dataset Information

A phase II study of cell cycle inhibitor UCN-01 in patients with metastatic melanoma: a California Cancer Consortium trial.

Background

Publications

A phase II study of cell cycle inhibitor UCN-01 in patients with metastatic melanoma: a California Cancer Consortium trial.

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