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

National Cancer Institute (NCI)

Status and phase: Active, not recruiting; Phase 2

Conditions: Refractory Lymphoma; Hematopoietic and Lymphoid Cell Neoplasm; Advanced Malignant Solid Neoplasm; Advanced Lymphoma; Refractory Malignant Solid Neoplasm

Treatments: Drug: Palbociclib

Study type: Interventional

Funder types: NIH

Identifiers

NCT04439201

U10CA180820 (U.S. NIH Grant/Contract)

U24CA196172 (U.S. NIH Grant/Contract)

EAY131-Z1B (Other Identifier)

NCI-2020-03171 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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. 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.

Enrollment: 40 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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40 participants in 1 patient group

Treatment (palbociclib)

Experimental group

Description:

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

Treatment:

Drug: Palbociclib