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

October 20, 2017 updated by: Merck Sharp & Dohme LLC

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

81

Phase

  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: 2 Hour SCH 727965 infusion
Participants treated with 2 hour SCH 727965 IV infusion
Drug: SCH 727965
SCH 727965 2 hour IV infusion on Day 1 of each 3 week cycle, administered in dose-escalating cohorts (Part 1 of the trial)
Drug: SCH 727965
SCH 727965 8 hour IV infusion on Day 1 of each 3 week cycle,in dose-escalating cohorts
Drug: SCH 727965
SCH 727965 24 hour IV infusion on Day 1 of each 3 week cycle, in dose-escalating cohorts
Drug: SCH 727965
SCH 727965 29.6 mg/m2 2 hour IV infusion on Day 1 of each 3 week cycle
EXPERIMENTAL: 8 Hour SCH 727965 infusion
Participants treated with 8 hour SCH 727965 IV infusion.
Drug: SCH 727965
SCH 727965 2 hour IV infusion on Day 1 of each 3 week cycle, administered in dose-escalating cohorts (Part 1 of the trial)
Drug: SCH 727965
SCH 727965 8 hour IV infusion on Day 1 of each 3 week cycle,in dose-escalating cohorts
Drug: SCH 727965
SCH 727965 24 hour IV infusion on Day 1 of each 3 week cycle, in dose-escalating cohorts
Drug: SCH 727965
SCH 727965 29.6 mg/m2 2 hour IV infusion on Day 1 of each 3 week cycle
EXPERIMENTAL: 24 Hour SCH 727965 infusion
Participants treated with 24 hour SCH 727965 IV infusion.
Drug: SCH 727965
SCH 727965 2 hour IV infusion on Day 1 of each 3 week cycle, administered in dose-escalating cohorts (Part 1 of the trial)
Drug: SCH 727965
SCH 727965 8 hour IV infusion on Day 1 of each 3 week cycle,in dose-escalating cohorts
Drug: SCH 727965
SCH 727965 24 hour IV infusion on Day 1 of each 3 week cycle, in dose-escalating cohorts
Drug: SCH 727965
SCH 727965 29.6 mg/m2 2 hour IV infusion on Day 1 of each 3 week cycle
EXPERIMENTAL: 2 Hour SCH 727965 infusions plus aprepitant in Cycle 1
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
SCH 727965 2 hour IV infusion on Day 1 of each 3 week cycle, administered in dose-escalating cohorts (Part 1 of the trial)
Drug: SCH 727965
SCH 727965 8 hour IV infusion on Day 1 of each 3 week cycle,in dose-escalating cohorts
Drug: SCH 727965
SCH 727965 24 hour IV infusion on Day 1 of each 3 week cycle, in dose-escalating cohorts
Drug: SCH 727965
SCH 727965 29.6 mg/m2 2 hour IV infusion on Day 1 of each 3 week cycle
Drug: Aprepitant
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.
Other Names:
  • Emend
Drug: Ondansetron
Ondansetron 32 mg IV 30 minutes prior to the SCH 727965 infusion on Day 1 of Cycles 1 and 2.
Other Names:
  • Zofran
Drug: Dexamethasone
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.
Other Names:
  • Decadron
EXPERIMENTAL: 2 Hour SCH 727965 infusion plus aprepitant in Cycle 2
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
SCH 727965 2 hour IV infusion on Day 1 of each 3 week cycle, administered in dose-escalating cohorts (Part 1 of the trial)
Drug: SCH 727965
SCH 727965 8 hour IV infusion on Day 1 of each 3 week cycle,in dose-escalating cohorts
Drug: SCH 727965
SCH 727965 24 hour IV infusion on Day 1 of each 3 week cycle, in dose-escalating cohorts
Drug: SCH 727965
SCH 727965 29.6 mg/m2 2 hour IV infusion on Day 1 of each 3 week cycle
Drug: Aprepitant
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.
Other Names:
  • Emend
Drug: Ondansetron
Ondansetron 32 mg IV 30 minutes prior to the SCH 727965 infusion on Day 1 of Cycles 1 and 2.
Other Names:
  • Zofran
Drug: Dexamethasone
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.
Other Names:
  • Decadron

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Safety and tolerability of SCH 727965, including maximum administered dose and dose-limiting toxicity
Time Frame: End of trial
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.
Time Frame: Cycle 1
Cycle 1

Secondary Outcome Measures

Outcome Measure
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.
Time Frame: Cycle 1 Days 1 and 2, and Cycle 2 Days 1 and 2
Cycle 1 Days 1 and 2, and Cycle 2 Days 1 and 2

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

October 11, 2006

Primary Completion (ACTUAL)

February 22, 2010

Study Completion (ACTUAL)

February 22, 2010

Study Registration Dates

First Submitted

March 26, 2009

First Submitted That Met QC Criteria

March 26, 2009

First Posted (ESTIMATE)

March 30, 2009

Study Record Updates

Last Update Posted (ACTUAL)

October 23, 2017

Last Update Submitted That Met QC Criteria

October 20, 2017

Last Verified

October 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P04630

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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