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

Advanced Malignant Solid Neoplasm Clinical Trial

Official title:

MATCH Treatment Subprotocol Z1C: Phase II Study of Palbociclib (PD-0332991) in Patients With Tumors With CDK4 or CDK6 Amplification

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT06390839
• Other study ID #: NCI-2024-01137
• Secondary ID: NCI-2024-01137EA
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 12, 2017
• Est. completion date: March 24, 2025

Study information

• Verified date: May 2024
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 49
• Est. completion date: March 24, 2025
• Est. primary completion date: March 24, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Lymphoma
• Advanced Malignant Solid Neoplasm
• Lymphoma
• Neoplasms
• Refractory Lymphoma
• Refractory Malignant Solid Neoplasm

Intervention

Procedure:
• Biopsy
Undergo biopsy
• Biospecimen Collection
Undergo blood sample collection
• Computed Tomography
Undergo CT scan
• Magnetic Resonance Imaging
Undergo MRI

Drug:
• Palbociclib
Given PO

Locations

Country	Name	City	State
United States	ECOG-ACRIN Cancer Research Group	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate (ORR)	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. 90% two-sided confidence interval is calculated for ORR. For the purposes of this study, patients should be re-evaluated for response: For treatments given in 21 day (3 week) cycles: every 3 cycles (9 weeks) for the first 33 cycles, and every 4 cycles thereafter (12 weeks); For treatments given in 28 day (4 week) cycles: every 2 cycles (8 weeks) for the first 26 cycles, and every three cycles thereafter (12 weeks); For treatments given in 42 day (6 week) cycles: every 2 cycles (12 weeks)	Up to 3 years
Secondary	Overall survival (OS)	Will be evaluated specifically for each drug (or step). OS will be estimated using the Kaplan-Meier method.	From start of treatment on that step until death, or censored at the date of last contact, assessed up to 3 years
Secondary	6-month progression free survival (PFS) rate	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.	From start of treatment on that step until determination of disease progression or death from any cause, censored at the date of last disease assessment for patients who have not progressed, assessed at 6 months
Secondary	Progression free survival	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.	From start of treatment on that step until determination of disease progression or death from any cause, censored at the date of last disease assessment for patients who have not progressed, assessed up to 3 years