Testing Palbociclib (PD-0332991) as Potentially Targeting Treatment in Cancers With CDK4 or CDK6 Amplification (MATCH - Subprotocol Z1C)

Phase 2

Active, not recruiting

Conditions: Advanced Lymphoma
Refractory Lymphoma
Refractory Malignant Solid Neoplasm
Advanced Malignant Solid Neoplasm

Interventions: Procedure: Biopsy Procedure
Procedure: Biospecimen Collection
Procedure: Computed Tomography
Procedure: Magnetic Resonance Imaging
Drug: Palbociclib

Registration Number: NCT06390839

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: This phase II MATCH treatment trial tests how well palbociclib (PD-0332991) works in treating patients with cancer that has certain genetic changes. Palbociclib (PD-0332991) is in a class of medications called kinase inhibitors. It is used in patients whose cancer has a certain mutation (change) in the CDK4 or CDK6 gene. It works by blocking the action of mutated CDK4 or CDK6 that signals cancer cells to multiply. This helps to stop or slow the spread of cancer cells.

Detailed Description: PRIMARY OBJECTIVE:

I. 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:

I. 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.

II. 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.

IV. 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 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo computed tomography (CT) or magnetic resonance imaging (MRI) and blood sample collection throughout the trial. Patients may also undergo a biopsy on study.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 1 year.

THE MATCH SCREENING TRIAL:

Please see NCT02465060 for information on the MATCH Screening Protocol and applicable documents.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 43

Inclusion Criteria

Patients must have met applicable eligibility criteria in the Master MATCH Protocol EAY131/ NCI-2015-00054 prior to registration to treatment subprotocol
Patients must have CDK4 amplification or CDK6 amplification, 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)
Patients must not have breast cancer, mantle cell lymphoma, myeloma, or liposarcoma
Patients must not have known hypersensitivity to palbociclib or compounds of similar chemical or biologic composition
Patients with known or symptoms of left ventricular dysfunction will be excluded
Patients must not have received prior therapy with a CDK4 or CDK6 inhibitor (including but not limited to palbociclib, abemaciclib, or ribociclib)
Patients must not be using drugs or foods that are known potent CYP3A4 inhibitors or inducers, or are CYP3A substrates with narrow therapeutic indices

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (palbociclib)	Biopsy Procedure	Patients receive palbociclib PO QD on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI and blood sample collection throughout the trial. Patients may also undergo a biopsy on study.
Treatment (palbociclib)	Biospecimen Collection	Patients receive palbociclib PO QD on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI and blood sample collection throughout the trial. Patients may also undergo a biopsy on study.
Treatment (palbociclib)	Computed Tomography	Patients receive palbociclib PO QD on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI and blood sample collection throughout the trial. Patients may also undergo a biopsy on study.
Treatment (palbociclib)	Magnetic Resonance Imaging	Patients receive palbociclib PO QD on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI and blood sample collection throughout the trial. Patients may also undergo a biopsy on study.
Treatment (palbociclib)	Palbociclib	Patients receive palbociclib PO QD on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI and blood sample collection throughout the trial. Patients may also undergo a biopsy on study.

Primary Outcome Measures

Name	Time	Method
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 analyzable patients. Objective response 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. Details about how to define complete response and partial response can be found in the master protocol. 90% two-sided binomial exact confidence interval is calculated for ORR.

Secondary Outcome Measures

Name	Time	Method
6-month Progression Free Survival (PFS) Rate	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, from which 6-month PFS rate is determined	Progression free survival is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. Disease progression was evaluated using the 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. Please refer to the protocol for detailed definitions of disease progression. 6 month PFS rate was estimated using the Kaplan-Meier method, which can provide a point estimate for any specific time point.
Progression Free Survival	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 was defined as time from treatment start date to date of disease progression or death from any causes, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Disease progression was evaluated using the 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. Please refer to the protocol for detailed definitions of disease progression.

Trial Locations

Locations (1): ECOG-ACRIN Cancer Research Group
🇺🇸
Philadelphia, Pennsylvania, United States
ECOG-ACRIN Cancer Research Group
🇺🇸Philadelphia, Pennsylvania, United States