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Anatomic Stage IV Breast Cancer AJCC v8Phase 2NCT04351230

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

A Phase 2 study testing Abemaciclib and Trastuzumab Emtansine in people with Anatomic Stage IV Breast Cancer AJCC v8 and HER2 Positive Breast Carcinoma, run by Academic and Community Cancer Research United at 6 sites in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Abemaciclib and Trastuzumab Emtansine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
6 sitesUnited States
Study dates
11 Nov 2020to 16 Feb 2022
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • PRE-REGISTRATION - INCLUSION CRITERIA
  • 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:
Show all 43Show fewer
  • 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
  • NOTE: Tumor lesions in a previously irradiated area are not considered measurable disease. Disease that is measurable by physical examination only is not eligible
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS): 0 or 1
  • Left ventricular ejection fraction (LVEF) >= 50% as determined by echocardiography or multiple-gated acquisition imaging =< 21 days prior to pre-registration
  • Able to swallow oral medication
  • Provide written informed consent =< 28 days prior to pre-registration
  • Willingness to return to enrolling institution for follow-up (during the active monitoring phase of the study)
  • Willingness to provide mandatory tissue specimens for correlative research
  • RANDOMIZATION - INCLUSION CRITERIA
  • Local, histological confirmation of metastatic HER2-positive breast cancer per American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines; one of the following must apply
  • 3+ by immunohistochemistry (IHC)
  • 2+ by IHC and in situ hybridization (ISH) amplified
  • Discontinued all cancer therapies (chemotherapy, radiotherapy, immunotherapy, and endocrine therapy), except trastuzumab, >= 21 days prior to randomization for myelosuppressive agents or >= 14 days prior to randomization for non-myelosuppressive agents
  • NOTE: All residual toxicities (except alopecia) should be at baseline or grade 1 (including peripheral neuropathy)
  • NOTE: If indicated, patients can commence treatment with bisphosphonates of RANK-L inhibitors (e.g., denosumab) any time prior to randomization. No washout period or treatment delay is required prior to commencing study treatment
  • Absolute neutrophil count >= 1.5 x 10^9/L (obtained =< 14 days prior to randomization)
  • Platelet count >= 100,000/mm^3 (obtained =< 14 days prior to randomization)
  • Hemoglobin >= 9.0 g/dL (obtained =< 14 days prior to randomization)
  • Creatinine =< 1.5 X upper limit of normal (ULN) (obtained =< 14 days prior to randomization)
  • Total bilirubin =< 1.5 x ULN (obtained =< 14 days prior to randomization) (except in cases of known Gilbert's syndrome where =< 2.0 x ULN is allowed and direct bilirubin within normal levels is permitted)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN (obtained =< 14 days prior to randomization)
  • NOTE: If liver metastases are present, AST and ALT =< 5 x ULN are acceptable
  • Prothrombin time (PT)/international normalized ratio (INR)/partial thromboplastin time (PTT) =< 1.5 X ULN OR if patient is receiving anticoagulant therapy and PT or PTT is within therapeutic range of intended use of coagulants (obtained =< 14 days prior to randomization)
  • Negative pregnancy test =< 7 days prior to randomization, for persons of childbearing potential only
  • NOTE: A female of childbearing potential must have a negative serum pregnancy test within 7 days of the first dose of T-DM1 +/- abemaciclib and agree to use a highly effective contraception method during the treatment period and for 6 months following the last dose of T-DM1 +/- abemaciclib
  • Women and men of reproductive potential should agree to use an appropriate method of birth control throughout their participation in this study due to the teratogenic potential of the therapy utilized in this trial. Appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives or double barrier method (diaphragm plus condom). Birth control must be used during the treatment period and continued for at least 6 months after the last dose of treatment with T-DM1 +/- abemaciclib
  • Cases of pregnancy that occur during maternal exposures to T-DM1+/- abemaciclib, or cases of pregnancy in female partners/spouses of male patients, should be reported. If a female patient is determined to be pregnant following T-DM1 +/- abemaciclib initiation, she must discontinue treatment immediately. Data on fetal outcome and breast-feeding are to be collected for regulatory reporting and drug safety evaluation
  • Willingness to provide mandatory blood specimens for correlative research

Who cannot join

  • PRE-REGISTRATION - EXCLUSION CRITERIA
  • 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
Show all 42Show fewer
  • 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
  • Any of the following =< 14 days prior to pre-registration:
  • Active bacterial infection (requiring intravenous [IV] antibiotics)
  • Fungal infection,
  • Detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C)
  • Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
  • Other active non-breast malignancy =< 3 years prior to pre-registrations
  • EXCEPTIONS: Patients with a history of adequately treated cancers that are of very low risk of recurrence (i.e. papillary thyroid cancer treated with surgery, carcinoma in situ of the cervix, non-melanoma skin cancer) are eligible
  • NOTE: If there is a history of prior malignancy, the patient must not be receiving other specific anti-neoplastic treatment
  • History of any of the following conditions:
  • Syncope of cardiovascular etiology
  • Ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation)
  • Sudden cardiac arrest
  • History of myocardial infarction =< 6 months prior to pre-registration or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
  • Received prior treatment with any CDK 4 and CDK 6 inhibitor (e.g. abemaciclib, ribociclib or palbociclib) or participated in any CDK 4 and CDK 6 inhibitor clinical trial for which treatment assignment is still blinded
  • Received live virus vaccine =< 28 days prior to pre-registration
  • Currently taking and unable to discontinue medications that are moderate or strong inhibitors and/or inducers of CYP3A or CYP3A4 before pre-registration
  • Unstable or newly diagnosed brain metastases requiring local treatment
  • NOTE: Stable treated brain metastases allowed
  • Specifically, central nervous system metastasis are allowed provided they have been treated (i.e., surgery, radiation, and/or radiosurgery) >= 12 weeks prior to pre-registration and have stable neurologic function, including no requirement for medication(s) to control symptoms for >= 2 weeks prior to pre-registration
  • NOTE: Patients with known leptomeningeal disease are not eligible
  • RANDOMIZATION - EXCLUSION CRITERIA
  • Unable to provide histological confirmation of metastatic or locally advanced HER2-positive breast cancer per ASCO CAP guidelines
  • Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
  • Pregnant persons
  • Nursing persons
  • Persons of childbearing potential who are unwilling to employ adequate contraception

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Michigan Cancer Research Consortium NCORP

    Ann Arbor, Michigan, 48106

  • Saint Vincent Hospital Cancer Center Green Bay

    Green Bay, Wisconsin, 54301

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • Carle Cancer Center NCI Community Oncology Research Program

    Urbana, Illinois, 61801

  • Yuma Regional Medical Center

    Yuma, Arizona, 85364

Other trials in United States

About this study

Official title: Phase II Trial of Abemaciclib and T-DM1 in Women and Men With HER2-positive Advanced or Metastatic Breast Cancer Who Progressed on Treatment With a Taxane, Trastuzumab and Pertuzumab

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess whether progression-free survival (PFS) is improved with the addition of abemaciclib to trastuzumab emtansine (T-DM1) for patients with estrogen receptor positive (ER+)HER2-positive advanced or metastatic breast cancer who progressed on treatment with a taxane, trastuzumab and pertuzumab (Cohort 1).

II. To assess whether progression-free survival (PFS) is improved with the addition of abemaciclib to T-DM1 for patients with estrogen receptor negative (ER-) HER2-positive advanced or metastatic breast cancer who progressed on treatment with a taxane, trastuzumab and pertuzumab (Cohort 2).

SECONDARY OBJECTIVES:

  1. To assess the safety and tolerability of each treatment regimen. II. To assess overall survival (OS) and objective response rate (ORR) of each treatment regimen.

CORRELATIVE RESEARCH OBJECTIVES:

  1. To assess whether the presence of vimentin expression or the level of tumor infiltrating lymphocytes (TILs) in the baseline tumor specimen is associated with an increased likelihood of longer PFS in the abemaciclib arms compared to the non-abemaciclib arms (regardless of ER status).

II. To assess both the baseline prognostic effects of circulating tumor cell (CTC) levels, ER expression in CTCs, HER2 expression in CTCs, serum TK1 levels, circulating tumor-derived deoxyribonucleic acid (ctDNA), ESR1, or PIK3CA mutations and whether a reduction in these levels after 2 cycles of treatment is associated with an increased likelihood of longer PFS overall and separately in the treatment arms.

III. To assess whether polymorphisms in FCgamma receptors (FCGR2A and FCGR3A) are associated with inferior PFS.

IV. To describe alterations seen in the peripheral blood immune system architecture after 2 cycles of treatment.

  1. To assess whether peripheral blood immune markers at baseline are prognostic and whether change in peripheral blood immune markers after 2 cycles of treatment are associated with PFS.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive T-DM1 intravenously (IV) over 90 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive T-DM1 IV over 90 minutes on day 1 and abemaciclib orally (PO) twice daily (BID) on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 6 months for up to 5 years.

Being tested
Abemaciclib, Trastuzumab Emtansine
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AbemaciclibDrug

    Also called LY-2835219, LY2835219, Verzenio

    Given IV

  • Trastuzumab EmtansineBiological

    Also called Ado Trastuzumab Emtansine, ADO-Trastuzumab Emtansine, Kadcyla, PRO132365

    Given PO

Study groups in NCT04351230
Study groupRoleWhat they receive
Arm A (trastuzumab emtansine)Active comparatorPatients receive trastuzumab emtansine IV over 90 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Trastuzumab Emtansine
Arm B (trastuzumab emtansine, abemaciclib)ExperimentalPatients 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.
Receives: Drug: Abemaciclib; Biological: Trastuzumab Emtansine

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (4)

  1. Incidence of adverse events

    Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be used to grade and assign attribution to each adverse event reported. For each treatment arm, the proportion of patients who report developing a grade 2-5 of this adverse event (AE) will be determined.

    Measured: Up to 5 years

  2. Overall response rate (ORR)

    ORR is defined as the number of patients whose disease meets the Response Evaluation Criteria in Solid Tumors (RECIST) for a partial (PR) or complete (CR) on two consecutive evaluations at least 12 weeks apart divided by the total number of patients in that cohort who started protocol treatment. For each treatment arm, a 90% binomial confidence interval will be constructed for the true overall response rate.

    Measured: Up to 5 years

  3. Duration of response

    For the patients whose disease responded to treatment by meeting the criteria for CR or PR on two consecutive evaluations at least 12 weeks apart, the duration of response will be tabulated.

    Measured: Up to 5 years

  4. Overall survival (OS)

    Overall survival estimates for each treatment arm will be determined using the Kaplan Meier method. This study was not designed to compare the OS distributions of these 2 treatment regimens. As such, no hypothesis testing will be performed. A point and interval estimate of the hazard of death 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.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Apr 2020
  2. Study start11 Nov 2020
  3. Primary completion16 Feb 2022
  4. Study completion16 Feb 2022

Why it stopped: There are no patients enrolled on this study and all efforts are being discontinued

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04351230
Sponsor's protocol ID
ACCRU-BR-1801
Other IDs
NCI-2020-02218, ACCRU-BR-1801, P30CA015083
Status last verified
Feb 2022
First submitted
15 Apr 2020
Last updated
26 May 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Abemaciclib and Trastuzumab Emtansine in people with Anatomic Stage IV Breast Cancer AJCC v8 and HER2 Positive Breast Carcinoma, run by Academic and Community Cancer Research United at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 43 inclusion and 42 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 26 May 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free survival (PFS) (time frame: The time elapsed between treatment initiation and tumor progression or death from any cause, assessed up to 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04351230.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 May 2022.

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