Dinaciclib in Treating Patients With Stage III-IV Melanoma

Stage IV Melanoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01026324
• Other study ID #: NCI-2013-00522
• Secondary ID: NCI-2013-0052209
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• First received: December 3, 2009
• Last updated: November 3, 2014
• Start date: September 2009

Study information

• Verified date: August 2014
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 12
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Melanoma
• Stage IIIB Melanoma
• Stage IIIC Melanoma
• Stage IV Melanoma

Intervention

Drug:
• dinaciclib
Given IV

Other:
• pharmacological study
Correlative studies
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	Dana-Farber Cancer Institute	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recommended phase-2 dose of SCH727965		14 days	Yes
Primary	Percentage of patients alive (Phase II)		Up to 1 year	No
Secondary	Progression-free survival		Up to 6 months	No
Secondary	Safety and incidence of adverse events as assessed by NCI CTCAE version 4.0	Frequency tables of worst grade of adverse event, drug-related adverse events, and worst grade of laboratory value will be presented by dose cohort	Up to 1 year after completion of treatment	Yes
Secondary	Change in cdk2, combined cdk2/1 and cdk9 inhibition in surrogate tissues and tumor by IHC		Baseline to 72 hours after courses 1 and 2	No