T-DM1 With or Without Abemaciclib for the Treatment of HER2-Positive Metastatic Breast Cancer

NCT04351230 | Withdrawn Phase 2 DMC FDA Drug

• 3 other identifiers: ACCRU-BR-1801NCI-2020-02218P30CA015083
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 6

Brief Summary

This phase II trial studies how well T-DMI with or without abemaciclib works for the treatment of HER2-positive breast cancer that has spread to other places in the body (metastatic). T-DM1 is a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug called DM1. Trastuzumab attaches to HER2 positive cancer cells in a targeted way and delivers DM1 to kill them. Abemaciclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving T-DM1 and abemaciclib may work better in treating patients with breast cancer compared to T-DM1 alone.

Conditions

Anatomic Stage IV Breast Cancer AJCC v8; HER2 Positive Breast Carcinoma; Metastatic Breast Carcinoma; Prognostic Stage IV Breast Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  For each treatment arm, the distribution of PFS times will be estimated using the Kaplan-Meier method. A stratified log rank test) will be used to assess whether the PFS is increased with the addition of abemaciclib to trastuzumab emtansine (T-DM1). Also, a point and interval estimate of the hazard of progression with abemaciclib plus T-DM1 relative to the hazard of progression with abemaciclib alone with be obtained from the results of fitting a stratified Cox model with treatment arm as the covariate.

  The time elapsed between treatment initiation and tumor progression or death from any cause, assessed up to 5 years

Secondary Outcomes (4)

• Incidence of adverse events

  Up to 5 years

• Overall response rate (ORR)

  Up to 5 years

• Duration of response

  Up to 5 years

• Overall survival (OS)

  From randomization to death due to any cause, assessed up to 5 years

Study Arms (2)

Arm A (trastuzumab emtansine)

ACTIVE COMPARATOR

Patients receive trastuzumab emtansine IV over 90 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Biological: Trastuzumab Emtansine

Arm B (trastuzumab emtansine, abemaciclib)

EXPERIMENTAL

Patients receive trastuzumab emtansine IV over 90 minutes on day 1 and abemaciclib PO BID on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: Abemaciclib; Biological: Trastuzumab Emtansine

Interventions

Abemaciclib DRUG

Given IV

Also known as: LY-2835219, LY2835219, Verzenio

Arm B (trastuzumab emtansine, abemaciclib)

Trastuzumab Emtansine BIOLOGICAL

Given PO

Also known as: Ado Trastuzumab Emtansine, ADO-Trastuzumab Emtansine, Kadcyla, PRO132365, RO5304020, T-DM1, Trastuzumab-DM1, Trastuzumab-MCC-DM1, Trastuzumab-MCC-DM1 Antibody-Drug Conjugate, Trastuzumab-MCC-DM1 Immunoconjugate

Arm A (trastuzumab emtansine); Arm B (trastuzumab emtansine, abemaciclib)

Eligibility Criteria

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

You may qualify if:

• Agree to undergo a core biopsy of breast cancer tissue derived from a local, regional or distant site for mandatory confirmation of ER+/ER-, progesterone receptor (PR) and HER2 status
• NOTE: If a single lesion is present, imaging must be completed after the lesion is biopsied and measurements must be taken from this image for disease evaluation by Response Evaluation Criteria in Solid Tumors (RECIST) to be considered eligible for this trial
• NOTE: The study requires a fresh biopsy for clinical and research purposes and archival tissue does not suffice. If the patient has already undergone a biopsy at the time of disease progression prior to enrolling on the trial, an additional research biopsy will still be required
• Imaging or histologic evidence of progression of unresectable locally advanced or metastatic breast cancer
• One of the following must be true:
• Progressed/relapsed during or within 12 months of completing neo-adjuvant treatment with a regimen containing a taxane, trastuzumab and pertuzumab
• Progressed/relapsed during or within 12 months of completing adjuvant treatment with a regimen containing a taxane, trastuzumab and pertuzumab
• Progressed/relapsed during metastatic treatment with a regimen containing a taxane, trastuzumab and pertuzumab
• Progressed/relapsed \> 12 months after receipt of adjuvant T-DM1
• A total of 1 or 2 prior lines of the following breast cancer therapies in any disease setting
• Chemotherapy alone
• HER2-directed therapy alone
• Chemotherapy with HER2 directed therapy
• Note: Any number of prior lines of endocrine therapy received in any disease setting
• Measurable disease as defined by RECIST criteria

You may not qualify if:

• Any of the following prior therapies:
• Surgery =\< 21 days prior to pre-registration
• Chemotherapy =\< 21 days prior to pre-registration
• Radiation =\< 14 days prior to pre-registration
• NOTE: Single fraction radiotherapy is allowed/exempt from this washout period
• NOTE: Must have fully recovered from the toxicities of therapy, except for alopecia or peripheral neuropathy
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
• NOTE: Examples include interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline grade 2 or higher diarrhea
• Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy which interacts with the study drug(s)
• 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

Sponsors & Collaborators

• Academic and Community Cancer Research United: lead
• National Cancer Institute (NCI): collaborator

Study Sites (6)

Yuma Regional Medical Center

Yuma, Arizona, 85364, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Carle Cancer Center NCI Community Oncology Research Program

Urbana, Illinois, 61801, United States

Location

Michigan Cancer Research Consortium NCORP

Ann Arbor, Michigan, 48106, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Saint Vincent Hospital Cancer Center Green Bay

Green Bay, Wisconsin, 54301, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

abemaciclib; Ado-Trastuzumab Emtansine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Maytansine; Macrolides; Lactones; Organic Chemicals; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Trastuzumab; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Ciara C O'Sullivan

  Academic and Community Cancer Research United

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2020
• First Posted: April 17, 2020
• Study Start: November 11, 2020
• Primary Completion: February 16, 2022
• Study Completion: February 16, 2022
• Last Updated: May 26, 2022

Record last verified: 2022-02

Locations

US (6)