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


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
Stage IIIB Melanoma, Stage IIIC Melanoma, Stage IV Melanoma

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Trial Information

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


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.


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

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Recommended phase-2 dose of SCH727965

Outcome Time Frame:

14 days

Safety Issue:

Yes

Principal Investigator

Frank Hodi

Investigator Role:

Principal Investigator

Investigator Affiliation:

Dana-Farber Cancer Institute

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2013-00522

NCT ID:

NCT01026324

Start Date:

September 2009

Completion Date:

Related Keywords:

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

Name

Location

Dana-Farber Cancer InstituteBoston, Massachusetts  02115