TRADE: Dose Escalation Tolerability of Abemaciclib in HR+ HER2- Early Stage Breast Cancer

NCT06001762 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 23-355
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 12

Brief Summary

In this research study, investigators are testing if a dose-increasing strategy for abemaciclib will have less side effects and be better tolerated than the standard dosage of abemaciclib for participants with early-stage high-risk hormone receptor positive breast cancer. The names of the study drugs involved in this study are:

• Abemaciclib (CDK4 and CDK6 inhibitor)
• Tamoxifen (Selective estrogen receptor modulator)
• Anastrozole/Letrozole (Non-steroidal aromatase inhibitors)
• Exemestane (steroidal aromatase inhibitor)
• LHRH (Gonadotropin-releasing hormone agonist, or Luteinizing hormone-releasing hormone agonist)

Conditions

Breast Cancer; Early-stage Breast Cancer; High Risk Breast Carcinoma

Keywords

Breast Cancer; Early-stage high-risk breast cancer; Early-stage breast cancer; High risk breast carcinoma

Outcome Measures

Primary Outcomes (1)

• Composite Adverse Rate at 3 months

  The rate of the composite endpoint will be reported, including disaggregated and combined rates of treatment discontinuations and/or dose reductions at 3 months.

  3 months

Secondary Outcomes (6)

• Incidence of Grade 2-4 Diarrhea

  Up to 26 weeks

• Composite Rate of Abemaciclib

  Up to 25 weeks

• Incidence of Treatment-Related Adverse Events

  Up to 25 weeks

• Rate of Inability to Reach the Full Dose

  Up to 25 weeks

• Therapeutic Adherence to Oral Adjuvant Therapy

  Up to 25 weeks

Study Arms (1)

Abemaciclib

EXPERIMENTAL

Study procedures will be conducted as follows: * Cycles 1 - 24 * Days 1 - 28 of 28-day cycle: Predetermined dose of Abemaciclib 2 x per day. * Endocrine therapy 1 x per day. * In clinic visits with blood tests, questionnaires, and assessments: * Day 1 of Cycles 1, 2, and 3 * Day 15 of Cycles 1 and 2 * Every three cycles after Cycle 3 Day 1. * End of treatment visit with blood tests, questionnaires, assessments, and stool sample collection.

Drug: Abemaciclib; Drug: Tamoxifen; Drug: Anastrozole; Drug: Letrozole; Drug: Exemestane; Drug: LHRH Agonist

Interventions

Abemaciclib DRUG

CDK4 and CDK6 inhibitor, tablet taken orally

Abemaciclib

Tamoxifen DRUG

Selective estrogen receptor modulator, taken orally per institutional standard of care

Abemaciclib

Anastrozole DRUG

Non-steroidal aromatase inhibitor, taken orally per institutional standard of care

Abemaciclib

Letrozole DRUG

Non-steroidal aromatase inhibitor, taken orally per institutional standard of care

Abemaciclib

Exemestane DRUG

Steroidal aromatase inhibitor, taken orally per institutional standard of care

Abemaciclib

LHRH Agonist DRUG

Luteinizing hormone-releasing hormone agonist), taken orally per institutional standard of care

Abemaciclib

Eligibility Criteria

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

You may qualify if:

• Stage II or III node-positive HR+/HER2- breast cancer per local laboratory assessment.
• Eligible participants must be appropriate candidates for adjuvant abemaciclib, per assessment of their treating physician.
• Participants must be candidates for adjuvant endocrine therapy, which may have started before or at time of entry onto the trial. Patient may be receiving adjuvant aromatase inhibitor or tamoxifen, +/- ovarian suppression.
• Participants must have undergone definitive surgery of the primary breast tumor(s) within 16 months of study entry.
• At least 21 days must have elapsed between last dose of chemotherapy and registration. Participants who previously received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events \[CTCAE\] Grade ≤1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to randomization.
• At least 14 days must have elapsed between end of radiotherapy and day 1 of treatment with abemaciclib. Participants who received prior radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. No radiotherapy should be planned to occur during study therapy.
• At least 14 days must have elapsed since most recent breast surgery prior to registration and patient has recovered from side effects of prior surgery.
• Bilateral or multifocal/multicentric breast cancers that meet eligibility criteria are allowed.
• ECOG performance status 0-1
• Men and women with any menopausal status ≥18 years of age
• Adequate organ function as defined below:
• Absolute neutrophil count (ANC) ≥ 1500 x 10\^9/L
• Platelets ≥ 100 x 10\^9/L
• Hemoglobin ≥ 8g/dL; patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin earlier than the day after the erythrocyte transfusion.
• Bilirubin ≤ 1.5 x ULN. For patients with Gilbert syndrome, the limit is ≤ 2 x institutional ULN AND direct bilirubin within the normal range of normality.

You may not qualify if:

• Prior treatment with any CDK4/6 inhibitor.
• Patients with node-negative breast cancer are not eligible for the trial.
• Concurrent therapy with other investigational agents.
• Diagnosis of inflammatory breast cancer (T4d).
• History of allergic reactions attributed to abemaciclib or similar chemical or biologic composition or excipients.
• Participants with a history of malignancy are ineligible except in the following circumstances:
• Individuals with a history of invasive breast cancer are not eligible unless they have been disease-free for a minimum of five years.
• Individuals with a malignancy history other than invasive breast cancer are eligible if they have no active malignancy and are deemed by the investigator to be at low risk for recurrence of that malignancy.
• Individuals with the following cancer history are eligible: adequately treated non- melanoma skin cancers, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS) of the breast, stage 1 grade 1 endometrial carcinoma. Other exceptions may exist following review with the sponsor-investigator
• Serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment \[e.g. estimated creatinine clearance \<30ml/min\], history of major surgical resection involving the stomach or small bowel, or preexisting uncontrolled Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea) or other conditions that in the opinion of the investigator limit compliance with study requirements.
• 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), or sudden cardiac arrest.
• Any of the following due to teratogenic potential of the study drugs:
• Pregnant women
• Nursing women
• Women of childbearing potential who are unwilling to employ adequate contraception (condoms, diaphragms, IUDS, surgical sterilization, abstinence, etc). Hormonal birth control methods are not permitted.

Sponsors & Collaborators

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

Study Sites (12)

Stamford Hospital

Stamford, Connecticut, 06904, United States

Location

Eastern Maine Medical Center (Northern Light)

Brewer, Maine, 04412, United States

Location

New England Cancer Specialists

Scarborough, Maine, 04074, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute at Steward St. Elizabeth's

Brighton, Massachusetts, 02135, United States

Location

Dana-Farber Cancer Institute at Foxborough

Foxborough, Massachusetts, 02035, United States

Location

Dana-Farber Cancer Institute at Merrimack Valley

Methuen, Massachusetts, 01844, United States

Location

Dana-Farber Cancer Institute at Milford

Milford, Massachusetts, 01757, United States

Location

Dana-Farber Cancer Institute at South Shore

South Weymouth, Massachusetts, 02190, United States

Location

Dana-Farber Cancer Insitute at Londonderry Hospital

Londonderry, New Hampshire, 03053, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

abemaciclib; Tamoxifen; Anastrozole; Letrozole; exemestane; Gonadotropin-Releasing Hormone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Nitriles; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Erica Mayer, MD, MPH

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

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: Principle Investigator

Study Record Dates

• First Submitted: August 14, 2023
• First Posted: August 21, 2023
• Study Start: October 5, 2023
• Primary Completion: January 22, 2025
• Study Completion (Estimated): January 1, 2027
• Last Updated: January 16, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (12)