Dinaciclib in Treating Patients With Advanced Melanoma



Status:Recruiting
Conditions:Skin Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:Any
Updated:2/4/2013
Start Date:September 2009

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


This phase I/II trial is studying the side effects and best dose of dinaciclib (SCH727965)
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


PRIMARY OBJECTIVES:

I. The primary objective of the phase 1 part of this study is to determine the recommended
phase 2 dose of SCH727965 administered as a 4-hour infusion every other week in patients
with advanced malignant melanoma.

II. The primary objective of the phase 2 part of this study is 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.

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:

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

After completion of study treatment, patients are followed up every 3 months .

Inclusion Criteria:

- Patients must have normal organ and marrow function as defined below:

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) =< 2.5 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

- 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

- 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

- 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 must have histologically confirmed, unresectable Stage III or Stage IV
malignant melanoma

- Patients must have received no more than one prior cytotoxic chemotherapycontaining
regimen for metastatic disease and no more than 2 prior treatment regimens overall
for metastatic disease

- ECOG performance status =< 1

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

- 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

- 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

- 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

- Pregnant women are excluded from this study because SCH727965 is an agent with the
potential for teratogenic or abortifacient effects

- 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
We found this trial at
3
sites
330 Brookline Ave
Boston, Massachusetts 02215
617-667-7000
Beth Israel Deaconess Medical Center Beth Israel Deaconess Medical Center (BIDMC) is one of the...
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185 Cambridge Street
Boston, Massachusetts 02114
617-724-5200
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Boston, Massachusetts 02115
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