Phase 1 Every-3-Week Dosing of SCH 727965 in Patients With Advanced Cancer (Study P04630)

Study Overview
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Brief Summary
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Part 1 and Part 2 of this trial will evaluate the safety, tolerability, maximum administered dose, and dose limiting toxicity of SCH 727965 administered every 3 weeks as a 2 hour intravenous (IV) infusion (Part 1), and as an 8-hour or 24-hour IV infusion (Part 2). Each 3-week period is considered one treatment cycle. Part 3 of this trial will evaluate the effect of coadministration of antiemetic drug aprepitant on the pharmacokinetics of SCH 727965 administered as a 2 hour IV infusion once every 3 weeks.

Official Title
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A Phase 1 Dose-Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of the Cyclin-Dependent Kinase (CDK) Inhibitor SCH 727965 Administered Every 3 Weeks in Subjects With Advanced Malignancies

Conditions
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Solid Tumors, Lymphoma, Non-Hodgkin, Multiple Myeloma

Intervention / Treatment
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* Drug: SCH 727965
* Drug: SCH 727965
* Drug: SCH 727965
* Drug: SCH 727965
* Drug: Aprepitant
* Drug: Ondansetron
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >=18 years, either sex, any race. Subjects must have histologically proven solid tumors, non-Hodgkin's lymphoma, or multiple myeloma. There must be no known standard therapy, or disease must be refractory to standard therapy. Eastern Cooperative Oncology Group performance status of 0, 1, or 2. Adequate hematologic, renal, and hepatic organ function and laboratory parameters. Exclusion Criteria: Symptomatic brain metastases or primary central nervous system malignancy. Previous radiation therapy to >25% of the total bone marrow. Previous treatment with SCH 727965. Known HIV infection.

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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2 Hour SCH 727965 infusion<br>Participants treated with 2 hour SCH 727965 IV infusion | Drug: SCH 727965<br>* SCH 727965 2 hour IV infusion on Day 1 of each 3 week cycle, administered in dose-escalating cohorts (Part 1 of the trial)<br>|
| Experimental: 8 Hour SCH 727965 infusion<br>Participants treated with 8 hour SCH 727965 IV infusion. | Drug: SCH 727965<br>* SCH 727965 8 hour IV infusion on Day 1 of each 3 week cycle,in dose-escalating cohorts<br>|
| Experimental: 24 Hour SCH 727965 infusion<br>Participants treated with 24 hour SCH 727965 IV infusion. | Drug: SCH 727965<br>* SCH 727965 24 hour IV infusion on Day 1 of each 3 week cycle, in dose-escalating cohorts<br>|
| Experimental: 2 Hour SCH 727965 infusions plus aprepitant in Cycle 1<br>Participants randomized to 2 Hour SCH 727965 infusion, plus concomitant ondansetron and dexamethasone in Cycles 1 and 2, and aprepitant in Cycle 1 only. | Drug: SCH 727965<br>* SCH 727965 29.6 mg/m2 2 hour IV infusion on Day 1 of each 3 week cycle<br>Drug: Aprepitant<br>* Oral aprepitant in Cycle 1 or Cycle 2, depending on the study arm: 125 mg 1 hour prior to the SCH 727965 infusion on Day 1, and 80 mg on Days 2 and 3.<br>* Other names: Emend;Drug: Ondansetron<br>* Ondansetron 32 mg IV 30 minutes prior to the SCH 727965 infusion on Day 1 of Cycles 1 and 2.<br>* Other names: Zofran;Drug: Dexamethasone<br>* Oral dexamethasone in Cycles 1 and 2: 12 mg 30 minutes prior to the SCH 727965 infusion on Day 1, and 8 mg in the morning on Days 2, 3, and 4.<br>* Other names: Decadron;|
| Experimental: 2 Hour SCH 727965 infusion plus aprepitant in Cycle 2<br>Participants randomized to 2 Hour SCH 727965 infusion, plus concomitant ondansetron and dexamethasone in Cycles 1 and 2, and aprepitant in Cycle 2 only. | Drug: SCH 727965<br>* SCH 727965 29.6 mg/m2 2 hour IV infusion on Day 1 of each 3 week cycle<br>Drug: Aprepitant<br>* Oral aprepitant in Cycle 1 or Cycle 2, depending on the study arm: 125 mg 1 hour prior to the SCH 727965 infusion on Day 1, and 80 mg on Days 2 and 3.<br>* Other names: Emend;Drug: Ondansetron<br>* Ondansetron 32 mg IV 30 minutes prior to the SCH 727965 infusion on Day 1 of Cycles 1 and 2.<br>* Other names: Zofran;Drug: Dexamethasone<br>* Oral dexamethasone in Cycles 1 and 2: 12 mg 30 minutes prior to the SCH 727965 infusion on Day 1, and 8 mg in the morning on Days 2, 3, and 4.<br>* Other names: Decadron;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of SCH 727965, including maximum administered dose and dose-limiting toxicity |  | End of trial | 
| In Part 1 and Part 2, pharmacodynamic effects of SCH 727965 with an ex vivo lymphocyte stimulation assay of participant's peripheral blood lymphocytes. |  | Cycle 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In Part 3, area under the plasma concentration versus time curve and maximum concentration of SCH 727965 administered as a 2 hour intravenous infusion with or without aprepitant in participants with advanced malignancies. |  | Cycle 1 Days 1 and 2, and Cycle 2 Days 1 and 2 |