Dinaciclib in Treating Patients With Stage IV Melanoma

Study Overview
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Brief Summary
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This phase II trial is studying the side effects and how well dinaciclib works in treating patients with stage IV melanoma. Dinaciclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Description
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PRIMARY OBJECTIVES: I. To assess the 1-year overall survival rate in patients with stage IV melanoma treated with dinaciclib. SECONDARY OBJECTIVES: I. To assess the 6-month progression-free survival rate in these patients. II. To evaluate the response rate (confirmed and unconfirmed complete and partial responses) in the subset of patients with measurable disease. III. To assess the safety and tolerability of dinaciclib given to patients with stage IV melanoma. OUTLINE: This is a multicenter study. Patients receive dinaciclib IV over 2 hours on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 months for up to 3 years.

Official Title
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A Phase II Trial of SCH 727965 (NSC 747135) in Patients With Stage IV Melanoma

Conditions
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Acral Lentiginous Melanoma, Cutaneous Nodular Melanoma, Lentigo Maligna Melanoma, Low-CSD Melanoma, Mucosal Melanoma, Recurrent Melanoma, Stage IV Cutaneous Melanoma AJCC v6 and v7

Intervention / Treatment
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* Drug: Dinaciclib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biopsy-confirmed malignant melanoma Stage IV disease Cutaneous or mucosal origin Melanoma of unknown primary allowed No ocular melanoma Measurable or non-measurable disease No prior or concurrent brain metastases as confirmed by CT scan or MRI Zubrod performance status 0-1 ANC ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 9 g/dL Serum bilirubin ≤ 1.5 times upper limit of normal (ULN) (including patients with hepatic metastases) SGOT or SGPT ≤ 2.5 times ULN (≤ 5 times ULN in the presence of hepatic metastases) Serum creatinine ≤ 1.5 times ULN Not pregnant or nursing Fertile patients must use effective contraception No other prior malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years No prior therapy with a cyclin-dependent kinase inhibitor At least 14 days since prior radiotherapy At least 28 days since prior systemic chemotherapy At least 28 days since prior adjuvant systemic therapy At least 28 days since prior surgery No more than 1 prior systemic therapy regimen (chemotherapy, biologic/immunotherapy, hormonal therapy, or a combination regimen) for stage IV melanoma and any side effects must have resolved to ≤ grade 1 Any number of prior adjuvant systemic therapy regimens allowed, including interferon alfa-2b, GM-CSF, chemotherapy, and chemobiotherapy Therapy for stage IV resected free-of-disease will be considered adjuvant therapy Prior radiotherapy allowed provided any side effects have resolved to ≤ grade 1 Prior surgery (for both the primary and stage IV disease) allowed provided side effects have resolved to ≤ grade 1 No other concurrent or planned non-study treatment (including chemotherapy, hormonal therapy, biologic therapy, or radiotherapy) No concurrent CYP3A4 inhibitors or inducers No concurrent grapefruit or grapefruit juice

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive dinaciclib IV over 2 hours on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. | Drug: Dinaciclib<br>* Given IV<br>* Other names: SCH 727965;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact. | Weekly, up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival Assessed by Response Evaluation Criteria for Solid Tumors (RECIST) | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. The duration from the date of randomization to the date of first documentation of progressive disease, symptomatic deterioration, or death dure to any cause. | Disease assessment was performed every 6 weeks, up to 3 years. | 
| Response Rate (Confirmed and Unconfirmed Complete and Partial Responses) Assessed by RECIST | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | Disease assessments for response were performed every 6 weeks, up to 3 years | 
| Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Adverse Events (AEs) are reported by CTCAE Version 3.0. Only adverse events that are possibly, probably or definitely related to study drug are reported. The outcome measure here is different from Serious Adverse Event, whose definition could be more strict and specific. The number of patients who suffers the certain adverse event listed here could be larger than the number listed in following serious adverse event. | Toxicity assessment was evaluated after each cycle (21 days), up to 3 years. |