Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Carcinoma

Breast Neoplasms

Breast Diseases

Skin Diseases

Bone Density Conservation Agents

Antineoplastic Agents

All Drugs and Chemicals

Tamoxifen

Hormones

Exemestane

Letrozole

Estrogens

Prolactin Release-Inhibiting Factors

Estrogen Receptor Modulators

Selective Estrogen Receptor Modulators

Anastrozole

Aromatase Inhibitors

Enzyme Inhibitors

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormone Antagonists

Antineoplastic Agents, Hormonal

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.

CDK4 and CDK6 inhibitor, tablet taken orally

Abemaciclib

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

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

Steroidal aromatase inhibitor, taken orally per institutional standard of care

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

LHRH Agonist

Erica Mayer, MD, MPH

K.M. Steve Lo, MD

Chiara Battelli, MD

Shana Berwick, MD

Alys Malcolm, MD

Natalie Sinclair, MD

Pedro Sanz-Altamira, MD

Natalie Sinclaire, MD

Meredith Faggen, MD

Meredith Faggeen, MD

Jeanna Walsh, MD

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)

This research study is a prospective, single-arm, open label, phase 2 study designed to evaluate 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.

This research study involves adjuvant abemaciclib plus endocrine (anti-hormone) therapy that works to target breast cancer. Adjuvant therapy is treatment given after surgery, chemotherapy, and/or radiation therapy.

The U.S. Food and Drug Administration (FDA) has approved abemaciclib as a treatment option for early-stage high-risk hormone receptor breast cancer. The FDA has also approved hormonal therapies as treatment for hormone receptor positive breast cancer.

The research study procedures include screening for eligibility, study treatment including laboratory evaluations and questionnaires, blood tests, tumor biopsies, and stool collections.

Participation in this research study is expected to last for at least 2 years and up to 5 years.

It is expected that about 90 people will take part in this research study.

Eli Lilly and Company is supporting this study by providing funding for the study and supplying the study drug, abemaciclib.

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

The TRADE Study: A Phase 2 Trial to Assess the ToleRability of Abemaciclib Dose Escalation in Patients With Early-Stage HR-positive and HER2-negative Breast Cancer

The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

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

Incidence of grade 2-4 diarrhea will be reported as frequencies and absolute numbers based on CTCAE5.0.

The composite rate will be reported, including disaggregated and combined rates of treatment discontinuations, dose reductions, dose holds, and inability to reach or maintain the target dose.

The incidence of treatment-related adverse events will be reported as frequencies and absolute numbers based on CTCAT5.0.

Rate of inability to reach the full dose will be reported as the rate of participants who have never reached the full dose at 150mg BID.

Ratio of the self-reported number of pills taken and number of pills prescribed

Rate of patients at full dose (150mg BID) at 12 w versus those unable to reach full dose

Spots Global Cancer Trial Database for high risk breast carcinoma