Clinical Trials /

Abemaciclib for Patients With Retinoblastoma-Positive, Triple Negative Metastatic Breast Cancer

NCT03130439

Description:

This research study is studying a drug called Abemaciclib as a possible treatment for have metastatic triple-negative type of breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Abemaciclib for Patients With Retinoblastoma-Positive, Triple Negative Metastatic Breast Cancer
  • Official Title: A Phase 2 Study of Abemaciclib for Patients With Retinoblastoma-Positive, Triple Negative Metastatic Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: 17-024
  • NCT ID: NCT03130439

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
AbemaciclibLY2835219Abemaciclib

Purpose

This research study is studying a drug called Abemaciclib as a possible treatment for have metastatic triple-negative type of breast cancer.

Detailed Description

      This research study is a Phase II clinical trial. Phase II clinical trials test the safety
      and effectiveness of an investigational intervention to learn whether the intervention works
      in treating a specific disease. "Investigational" means that the intervention is being
      studied.

      The FDA (the U.S. Food and Drug Administration) has not approved abemaciclib as a treatment
      for any disease.

      Some triple-negative breast cancers show expression of the Rb protein and are referred to as
      "Rb-positive." The Rb protein is important because it controls the way that cancer cells
      divide and grow. Drugs like abemaciclib work by changing the way that Rb functions. This can
      potentially stop cancer cells from dividing, and can also potentially lead to cancer cell
      death.

      In this research study, the investigators are are looking to see how safe abemaciclib is and
      how well it will work to help people with triple-negative breast cancer that is Rb-positive.
    

Trial Arms

NameTypeDescriptionInterventions
AbemaciclibExperimental-Abemaciclib will be administered orally, twice daily on days 1 to 28
  • Abemaciclib

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed invasive breast cancer,
             which is recurrent, locally advanced, unresectable or metastatic.

          -  Patients must have at least one lesion that is not within a previously radiated field
             and that is measurable on computerized tomography (CT) or magnetic resonance imaging
             (MRI) scans per RECIST version 1.1. Bone lesions are not considered measurable.

          -  Either the primary tumor and/or metastatic tumor must be triple-negative on the most
             recent sample as defined below:

               -  Hormone receptor status: the invasive tumor must be ER- and PR-negative, or
                  staining present in <1% by immunohistochemistry (IHC)

               -  HER2 status: the invasive tumor must be Human Epidermal Growth Factor Receptor 2
                  Negative (HER2-negative) by the ASCO CAP guidelines

          -  Either the primary tumor and/or the metastatic tumor must be RB positive as defined
             below:

             --RB status: the invasive tumor must have greater than 10% of tumor cells staining
             positive for RB.

          -  Prior Chemotherapy:

               -  Patients may have received 1-3 prior chemotherapeutic regimens for metastatic
                  disease OR

               -  Patients must have developed recurrent/metastatic disease within 6 months of
                  completing an anthracycline and taxane containing (neo)-adjuvant therapy regimen
                  for triple-negative breast cancer.

               -  Patients must have been off treatment with myelosuppressive chemotherapy for at
                  least 21 days or nonmyelosuppressive agents for 14 days before registration.
                  Patients should also be adequately recovered (to baseline or grade 1) from acute
                  toxicities of prior treatment except for residual alopecia and peripheral
                  neuropathy.

          -  Prior biologic therapy: Patients must have discontinued all biologic therapy at least
             21 days before registration.

          -  Prior radiation therapy: Patients may have received prior radiation therapy in either
             the metastatic or early-stage setting. Radiation therapy must be completed at least
             14 days prior to study registration.

          -  Patients on bisphosphonates or RANK-L inhibitors may continue receiving these
             therapies dur¬ing study treatment. There is no washout period required between the
             last dose of these therapies and the start of abemaciclib.

          -  The patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0-1

          -  Patients must have normal organ and marrow function as defined below:

               -  Absolute neutrophil count ≥1500/mm3

               -  Platelets ≥100,000/mm3

               -  Hemoglobin ≥8 g/dL

               -  Total Bilirubin ≤1.5x the upper limit of normal (ULN)

               -  Serum creatinine ≤1.5 mg/dL OR calculated GFR ≥60mL/min

               -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 times the
                  upper limit of normal. For patients with documented liver metastases, AST/ALT ≤
                  5.0 times the upper limit of normal.

          -  Female subjects of childbearing potential must have a negative serum pregnancy test
             at screening. Women of childbearing potential are defined as those who have not been
             surgically sterilized and have had a menstrual period in the past year

          -  The patient must be ≥18 years old

          -  Capable of understanding and complying with the protocol and has signed the informed
             consent document.

          -  Able to swallow study drug.

          -  Sexually active patients (male and female) must use medically acceptable methods of
             contraception during the course of the study and for 3 months after completion of
             study treatment. If a woman becomes pregnant or suspects she is pregnant while
             participating in this study, she should inform her treating physician immediately.
             While on the study and for 3 months after final drug administration, women may not
             breast-feed.

          -  Confirmed availability of formalin-fixed, paraffin-embedded (FFPE) tumor tissue

          -  Patients with tumor that is felt to be accessible to biopsy must be willing to
             provide tissue from a newly obtained core biopsy of a tumor lesion at baseline.
             Biopsies will be obtained up to 1 week (7 days) prior to initiation of treatment on
             Cycle 1, Day 1. Patients who undergo an attempted research biopsy procedure for the
             purpose of this protocol, and in whom inadequate tissue is obtained, are not required
             to undergo a repeat biopsy in order to continue on protocol.

        Exclusion Criteria:

          -  Received a prior CDK4/6 inhibitor.

          -  Undergone major surgery within 14 days of the initial dose of study drug

          -  Received another investigational agent (defined as any agent/device that has not
             received regulatory approval for any indication) within 14 days of the first dose of
             study drug for a nonmyelosupressive agent, or 21 days of the first dose of study drug
             for a myelosuppressive agent.

          -  Has any severe concurrent disease, infection, or comorbid condition that renders the
             patient inappropriate for enrollment in the opinion of the investigator.

          -  Has an active bacterial, fungal, and/or known viral infection. Patients with known
             HIV infection are excluded given the potential for interactions between
             antiretroviral agents and abemaciclib, and the potential for increased risk of
             life-threatening infection with therapy that is myelosuppressive. Patients with known
             Hepatitis B or Hepatitis C infection are excluded only if there is evidence of active
             infection (detectable Hepatitis B surface antigen, detectable Hepatitis C RNA)

          -  Documented brain metastases that are untreated, symptomatic, or require therapy to
             control symptoms. Participants with previously diagnosed brain metastases are
             eligible if they have completed treatment at least one month prior to trial
             registration, are neurologically stable, and have recovered from effects of
             radiotherapy or surgery.

               -  Any corticosteroid use for brain metastases must have been discontinued without
                  the subsequent appearance of symptoms for ≥2 weeks before the first study drug.

               -  Treatment for brain metastases may have included whole brain radiotherapy,
                  radiosurgery, or a combination as was deemed appropriate by the treating
                  physician.

               -  Patients who meet the above criteria and are clinically stable on
                  anti-convulsant medication are eligible only if their anti-convulsant does not
                  alter hepatic cytochrome P450 activity in a way that might interfere with
                  metabolism of abemaciclib.

          -  Pregnant women are excluded from this study because of the potential for teratogenic
             effects.

          -  Lactating women are excluding from the study.

          -  Individuals with a history of a second malignancy are ineligible except for the
             following circumstances: individuals with a history of other malignancies are
             eligible if they have been disease-free for at least 5 years and are deemed by the
             investigator to be at low risk for recurrence of that malignancy. Individuals with
             the following cancers are eligible if they are diagnosed and have completed treatment
             within the past 5 years: cervical cancer in situ, and non-melanoma cancer of the
             skin. Patients with other cancers diagnosed within the past 5 years and felt to be at
             low risk of recurrence should be discussed with the principle investigator to
             determine eligibility.

          -  Have received any live vaccination within 28 days of first dose of study drug.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate
Time Frame:2 years
Safety Issue:
Description:ORR as confirmed Complete Response (CR) or Partial Response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST)

Secondary Outcome Measures

Measure:Progression Free Survival
Time Frame:2 years
Safety Issue:
Description:
Measure:Overall Survival
Time Frame:2 years
Safety Issue:
Description:
Measure:Disease Control Rate
Time Frame:2 years
Safety Issue:
Description:
Measure:Clinical Benefit Rate
Time Frame:2 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Breast Cancer

Last Updated

April 26, 2017