A Phase II Study of the CDK4/6 Inhibitor Abemaciclib in Patients With Solid Tumors Harboring Genetic Alterations in Genes Encoding D-Type Cyclins or Amplification of CDK4 or CDK6
Overview
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Dana-Farber Cancer Institute
- Enrollment
- 38
- Locations
- 2
- Primary Endpoint
- Progression-Free Rate
Overview
Brief Summary
This research study is studying a targeted therapy as a possible treatment for cancer abnormality in one of the following genes: CCND1, CCND2, CCND3, CDK4, or CDK6.
The drug involved in this study is:
-Abemaciclib
Detailed Description
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.
The FDA (the U.S. Food and Drug Administration) has not approved Abemaciclib as a treatment for any disease.
To participate in this study, the participant must have an abnormality in one of the following genes: CCND1, CCND2, CCND3, CDK4, or CDK6. Abnormalities in these genes may cause the cancer to grow more rapidly. CDK4 and CDK6 are proteins that are involved with the cell growth process. D-type cyclins (CCND1, CCND2, and CCND3) are proteins that help control the activity of CDK4 and CDK6.
Abemaciclib is being studied as a treatment for people with advanced cancer. Abemaciclib is a cyclin-dependent kinase (CDK) inhibitor. CDK inhibitors work to stop cell growth. In this research study, the investigators are hoping to learn whether Abemaciclib can be used to slow or stop the growth of cancers with specific genetic abnormalities.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Participants must have a histologically or cytologically confirmed advanced solid tumor of a non-breast origin, for which standard therapy proven to provide clinical benefit does not exist or is no longer effective.
- •For enrollment to Arm 1: Participants must have a confirmed CCND1, 2, or 3 high-level amplification, CCND1 mutation, or a CCND1 splice variant expected to lead to nuclear retention of cyclin D1 protein, via DFCI/BWH OncoPanel or any CLIA-certified method.
- •For enrollment to Arm 2: Participants must have a confirmed CDK4 or CDK6 high-level amplification, identified via DFCI/BWH OncoPanel or any CLIA-certified method.
- •Participants must have evaluable or measurable disease.
- •Age ≥ 18 years.
- •ECOG performance status of 0-1 (see APPENDIX A).
- •Participants must have normal organ and marrow function as defined below:
- •Absolute neutrophil count ≥1,500/mcL
- •Platelets ≥100,000/mcL
- •Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN)
Exclusion Criteria
- •Participants who have had chemotherapy, biologic therapy, investigational agents, radiotherapy, or major surgery within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study.
- •Participants who have had oral targeted therapy or oral tyrosine kinase inhibitors (TKIs) within 5 half-lives prior to entering the study.
- •Participants who have received prior treatment with a CDK4/6 inhibitor.
- •Participants must have recovered to eligibility levels from prior toxicity or adverse events as a result of previous treatment prior to entering the study.
- •Participants who are receiving any other investigational agents.
- •Participants with hematologic lymphoma.
- •Participants with symptomatic CNS metastases who are neurologically unstable and/or require radiation therapy are excluded.
- •Participants with brain metastases that do not meet the above criteria in the opinion of the treating investigator are allowed.
- •Symptomatic disease is allowed as long as symptoms are controlled and stable.
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to abemaciclib.
Arms & Interventions
Participants with CCND1, CCND2, or CCND3
- Abemaciclib will be administered orally on a daily basis
- Dosage will be determine by the PI
Intervention: Abemaciclib (Drug)
Participants with CDK4 or CDK6
- Abemaciclib will be administered orally on a daily basis
- Dosage will be determine by the PI
Intervention: Abemaciclib (Drug)
Outcomes
Primary Outcomes
Progression-Free Rate
Time Frame: 4 months
proportion of patients who are alive and progression-free at 4 months on both arms.
Secondary Outcomes
- Overall Response Rate(2 years)
- Toxicity(2 years)
- Adverse events by CTCAE 4.03(2 years)
Investigators
Geoffrey Shapiro, MD, PhD
Principal Investigator
Dana-Farber Cancer Institute