Clinical Trials /

Study of the CDK4/6 Inhibitor Abemaciclib in Solid Tumors Harboring Genetic Alterations in Genes Encoding D-type Cyclins or Amplification of CDK4 or CDK6

NCT03310879

Description:

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

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of the CDK4/6 Inhibitor Abemaciclib in Solid Tumors Harboring Genetic Alterations in Genes Encoding D-type Cyclins or Amplification of CDK4 or CDK6
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: 17-343
  • NCT ID: NCT03310879

Conditions

  • Cancer

Interventions

DrugSynonymsArms
AbemaciclibParticipants with CCND1, CCND2, or CCND3

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Participants with CCND1, CCND2, or CCND3ExperimentalAbemaciclib will be administered orally on a daily basis Dosage will be determine by the PI
  • Abemaciclib
Participants with CDK4 or CDK6ExperimentalAbemaciclib will be administered orally on a daily basis Dosage will be determine by the PI
  • Abemaciclib

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-Free Rate
Time Frame:4 months
Safety Issue:
Description:proportion of patients who are alive and progression-free at 4 months on both arms.

Secondary Outcome Measures

Measure:Overall Response Rate
Time Frame:2 years
Safety Issue:
Description:objective response rate by RECIST 1.1 for patients enrolled to both arms.
Measure:Toxicity
Time Frame:2 years
Safety Issue:
Description:Adverse event data in all participants by CTCAE 4.03

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Cancer

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