Testing Palbociclib (PD-0332991) as a Potential Targeted Treatment in Cancers With CCND1, 2, 3 Amplification (MATCH-Subprotocol Z1B)

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Active, not recruiting
CT.gov ID
NCT04439201
Collaborator
(none)
70
1
1

Study Details

Study Description

Brief Summary

This phase II MATCH treatment trial identifies the effects of palbociclib in patients whose cancer has genetic changes called CCND1, 2, or 3 amplification. Palbociclib blocks proteins called CDK4 and CDK6, which may stop cancer cell growth when CCND1, 2, or 3 amplifications are present. Researchers hope to learn if palbociclib will shrink this type of cancer or stop its growth.

Detailed Description

PRIMARY OBJECTIVE:
  1. To evaluate the proportion of patients with objective response (OR) to targeted study agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma.
SECONDARY OBJECTIVES:
  1. To evaluate the proportion of patients alive and progression free at 6 months of treatment with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple myeloma.

  2. To evaluate time until death or disease progression. III. To identify potential predictive biomarkers beyond the genomic alteration by which treatment is assigned or resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and imaging-based assessment platforms.

  3. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes from pre- through post-therapy imaging can predict objective response and progression free survival and to evaluate the association between pre-treatment radiomic phenotypes and targeted gene mutation patterns of tumor biopsy specimens.

OUTLINE:

Patients receive palbociclib orally (PO) once daily (QD) on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months if less than 2 years from study entry, and then every 6 months for year 3 from study entry.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
70 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
MATCH Treatment Subprotocol Z1B: Phase II Study of Palbociclib (PD-0332991) in Patients With Tumors With CCND1, 2, 3 Amplification
Actual Study Start Date :
May 31, 2016
Anticipated Primary Completion Date :
Jun 30, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment (palbociclib)

Patients receive palbociclib PO QD days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity

Drug: Palbociclib
Given PO
Other Names:
  • 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-8h-pyrido(2,3-d)pyrimidin-7-one
  • Ibrance
  • PD 0332991
  • PD 332991
  • PD 991
  • PD-0332991
  • Outcome Measures

    Primary Outcome Measures

    1. Objective response rate (ORR) [Tumor assessments occurred at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration]

      ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among eligible and treated patients. Objective response rate is defined consistent with Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. For each treatment arm, 90% two-sided binomial exact confidence interval will be calculated for ORR.

    Secondary Outcome Measures

    1. Overall survival (OS) [Assessed every 3 months for =< 2 years and every 6 months for year 3]

      OS is defined as time from treatment start date to date of death from any cause. Patients alive at the time of analysis are censored at last contact date. OS will be evaluated specifically for each drug (or step) using the Kaplan-Meier method.

    2. Progression free survival (PFS) [Assessed at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration]

      PFS is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. PFS will be estimated using the Kaplan-Meier method.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol

    • Patients must have amplification of CCND1, 2, or 3, or another aberration, as determined via the MATCH Master Protocol

    • Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block)

    Exclusion Criteria:
    • Patients must not have known hypersensitivity to palbociclib or compounds of similar chemical or biologic composition

    • Patients must not have breast cancer, mantle cell lymphoma or myeloma

    • Patients with known or symptoms of left ventricular dysfunction will be excluded

    • Patients must not have had prior treatment with palbociclib, ribociclib, abemaciclib or any other CDK4/6 inhibitors

    • Patients must not be using drugs or foods that are known potent CYP3A4 inhibitors or inducers, or are CYP3A4 substrates with narrow therapeutic indices

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 ECOG-ACRIN Cancer Research Group Philadelphia Pennsylvania United States 19103

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Amy S Clark, ECOG-ACRIN Cancer Research Group

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT04439201
    Other Study ID Numbers:
    • NCI-2020-03171
    • NCI-2020-03171
    • EAY131-Z1B
    • EAY131-Z1B
    • U10CA180820
    • U24CA196172
    First Posted:
    Jun 19, 2020
    Last Update Posted:
    Jun 30, 2022
    Last Verified:
    Feb 1, 2022
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jun 30, 2022