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

NCT03130439 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 17-024
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Breast Cancer

Keywords

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR; Overall Response Rate(ORR) = (CR + PR)/sample size.

  2 years

Secondary Outcomes (4)

• Progression Free Survival

  Baseline to the earlier of progression (per Response Evaluation Criteria in Solid Tumors 1.1), date of death due to any cause, or date of last disease evaluation. Participants will be followed up up to 16.5 months.

• Overall Survival

  Baseline to date of death due to any cause, or at date last known alive.Participants will be followed once every 6 months until death.Those removed from protocol therapy for unacceptable adverse event(s) will be followed until resolution or stabilization.

• Disease Control Rate

  2 years

• Clinical Benefit Rate

  2 years

Study Arms (1)

Abemaciclib

EXPERIMENTAL

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

Drug: Abemaciclib

Interventions

Abemaciclib DRUG

Abemaciclib (LY2835219) has been shown in vitro to be a selective ATP-competitive inhibitor of CDK4 and CDK6 kinase activity that prevents the phosphorylation and subsequent inactivation of the Rb tumor suppressor protein, thereby inducing G1 cell cycle arrest and inhibition of cell proliferation.

Also known as: LY2835219

Abemaciclib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 50% of tumor cells staining positive for RB.
• Prior Chemotherapy:
• Patients may have received 1-3 prior systemic therapies for metastatic disease (note: for patients who have first developed recurrent/metastatic disease within 12 months of completing any (neo)-adjuvant therapy for triple-negative breast cancer, the (neo)-adjuvant therapy is counted as a prior line of therapy).
• 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 during 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:

You may not qualify if:

• 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.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Eli Lilly and Company: collaborator

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

abemaciclib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Sara Tolaney, MD, MPH
• Organization: Dana-Farber Cancer Institute

Sara_Tolaney@dfci.harvard.edu

617-632-5743

Study Officials

• Sara Tolaney, MD, MPH

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 24, 2017
• First Posted: April 26, 2017
• Study Start: May 26, 2017
• Primary Completion: August 18, 2021
• Study Completion: January 30, 2022
• Last Updated: February 20, 2026
• Results First Posted: September 22, 2022

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)