Dinaciclib in Treating Patients With Stage III-IV Melanoma

A Phase 1/2 Study of SCH727965 in Patients With Malignant Melanoma

This is a phase I/II trial is studying the side effects and best dose of dinaciclib and to see how well it works in treating patients with advanced melanoma. Dinaciclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Study Overview

• Status: Terminated
• Conditions: Stage IV Melanoma; Stage IIIB Melanoma; Stage IIIC Melanoma
• Intervention / Treatment: Other: laboratory biomarker analysis; Other: pharmacological study; Drug: dinaciclib

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the recommended phase 2 dose of SCH727965 administered as a 4-hour infusion every other week in patients with advanced malignant melanoma. (Phase I) II. To determine the 1-year overall survival of patients with malignant melanoma treated with SCH727965 at the dose and schedule derived in the phase 1 part of the study. (Phase II)

SECONDARY OBJECTIVES:

I. To characterize the safety profile and toxicities of SCH727965 administered as a 4-hour infusion every other week.

II. To determine the pharmacokinetics of SCH727965 administered as a 4-hour infusion every other week.

III. To determine the proportion of patients with malignant melanoma who are alive without progression of disease 6 months after beginning treatment with SCH727965 at the dose and schedule derived in the phase 1 part of the study.

IV. To determine the objective response rate to SCH727965 of patients with malignant melanoma enrolled to part 2 of the study.

V. To document cdk2, combined cdk2/1 and cdk9 inhibition in surrogate tissues and tumor.

VI. To correlate the degree of change of pharmacodynamic parameters in post-treatment compared to pre-treatment samples with clinical outcome.

VII. To correlate the degree of change of parameters defining cdk2, cdk2/1 and cdk9 inhibition with pharmacokinetic parameters.

VIII. To correlate pre-treatment cdk2 levels with the degree of change of parameters measuring cdk2 inhibition.

IX. To correlate pre-treatment cdk2 levels with clinical outcome. X. To correlate tumor p53 status with clinical outcome.

OUTLINE: This is a phase I dose-escalation study followed by a phase II study.

Patients receive dinaciclib IV over 4 hours on day 1. Courses repeat every 14 days in the absence of disease progression and unacceptable toxicity.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must have histologically confirmed, unresectable stage III or stage IV malignant melanoma
• ECOG performance status =< 1
• Absolute neutrophil count >= 1.5 x 10^9/L
• Platelets >= 100 x 10^9/L
• Total bilirubin within normal institutional limits
• AST(SGOT)/ALT(SGPT =< 1.5 x institutional upper limit of normal
• Creatinine =< 1.5 mg/dl OR
• Creatinine clearance >= 50 mL/min for patients with creatinine levels above institutional normal
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Eligible patients must agree to pre- and post-treatment biopsies of normal skin; in the phase 1 part of the study, patients with cutaneous disease or accessible lymph nodes must also agree to pre- and post-treatment tumor biopsies; in the phase 2 part of the study, tumor biopsies are required of the first 20 patients enrolled who have cutaneous disease or accessible lymph nodes
• Patients enrolled to the Phase 2 portion of the study must have measurable disease by RECIST criteria
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Patients who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier
• Patients may not be receiving any other investigational agents
• Patients with active CNS metastases are excluded; patients with a history of CNS metastases that have been treated must be stable for 4 weeks after completion of treatment, with image documentation required; patients must not be taking enzyme-inducing anticonvulsants and must be either off steroids or be receiving a stable dose of steroids
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with SCH727965
• HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with SCH727965; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
• Patients with other currently active malignancies are excluded, except those with an in-situ cancer or basal or squamous cell carcinoma of the skin
• In the phase 2 part of the study, patients who have received prior investigational treatment with a cdk inhibitor are excluded

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (dinaciclib); Patients receive dinaciclib IV over 4 hours on day 1. Courses repeat every 14 days in the absence of disease progression and unacceptable toxicity.	Other: laboratory biomarker analysis; Correlative studies; Other: pharmacological study; Correlative studies; Other Names: pharmacological studies; Drug: dinaciclib; Given IV; Other Names: SCH 727965; CDK inhibitor SCH 727965; cyclin-dependent kinase inhibitor SCH 727965

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recommended Phase-2 Dose of SCH727965	Due to difficult accrual to the trial, enrollment was ended early without determination of an MTD.	14 days
Percentage of Patients Alive (Phase II)	Due to difficult accrual to the trial, enrollment was ended early without entering into Phase II	Up to 1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression-free Survival	Up to 6 months

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Frank Hodi, Dana-Farber Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2009
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: December 3, 2009
• First Submitted That Met QC Criteria: December 3, 2009
• First Posted (Estimate): December 4, 2009

Study Record Updates

• Last Update Posted (Actual): April 4, 2017
• Last Update Submitted That Met QC Criteria: March 3, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Cyclin-Dependent Kinase Inhibitor Proteins
• Other Study ID Numbers: NCI-2013-00522 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U01CA062490 (U.S. NIH Grant/Contract); P30CA006516 (U.S. NIH Grant/Contract); 8296 (Other Identifier: CTEP); 09-152 (Other Identifier: Dana-Farber Cancer Institute)