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.
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)
- AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional (ULN) -OR-
- AST(SGOT)/ALT(SGPT) ≤ 5 × institutional (ULN) if liver metastases are present
- Serum Creatinine ≤ 1.5 × institutional ULN -OR-
- Creatinine clearance ≥ 60 mL/min (Cockroft-Gault Equation)
- The effects of abemaciclib on the developing human fetus are unknown. For this reason
women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry, for
the duration of study participation, and for 3 months after completion of abemaciclib
administration. Should a woman become pregnant or suspect she is pregnant while she or
her partner is participating in this study, she should inform her treating physician
immediately. A negative serum pregnancy test is required for women of childbearing
potential prior to study entry.
- Ability to understand and the willingness to sign a written informed consent document.
- Ability to swallow and retain oral medication.
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.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.
- Pregnant women are excluded from this study because abemaciclib is an agent with the
potential for teratogenic or abortifacient effects. Because there is an unknown but
potential risk for adverse events in nursing infants secondary to treatment of the
mother with abemaciclib, breastfeeding should be discontinued if the mother is treated
with abemaciclib. A negative serum pregnancy test is required for women of
childbearing potential prior to study entry.
- Participants with known HIV-positive status are ineligible because these participants
are at increased risk of lethal infections when treated with marrow-suppressive
therapy. Appropriate studies will be undertaken in participants receiving combination
antiretroviral therapy when indicated.
- Participants with known active Hepatitis B or Hepatitis C.
- Participants receiving an enzyme-inducing antiepileptic drug (EIAED) who cannot be
transferred to a non-EIAED (e.g., levetiracetam, lacosamide, lamotrigine, etc.) prior
to the initiation of protocol therapy.
