Abemaciclib in Treating Patients With Surgically Resectable, Chemotherapy Resistant, Triple Negative Breast Cancer

NCT03979508 | Terminated Phase 2 DMC FDA Drug

• 3 other identifiers: MC1734NCI-2019-0356717-010660
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 3

Brief Summary

This phase II trial studies how well abemaciclib works in treating patients with triple negative breast cancer that can be removed by surgery (resectable) and does not respond to treatment with chemotherapy alone, or in combination with pembrolizumab. Abemaciclib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Conditions

Anatomic Stage I Breast Cancer AJCC v8; Anatomic Stage II Breast Cancer AJCC v8; Anatomic Stage III Breast Cancer AJCC v8; Breast Ductal Carcinoma In Situ; Breast Fibrocystic Change; Breast Lobular Carcinoma In Situ; Invasive Breast Carcinoma; Prognostic Stage I Breast Cancer AJCC v8; Prognostic Stage IA Breast Cancer AJCC v8; Prognostic Stage IB Breast Cancer AJCC v8; Prognostic Stage II Breast Cancer AJCC v8; Prognostic Stage IIA Breast Cancer AJCC v8; Prognostic Stage IIB Breast Cancer AJCC v8; Prognostic Stage III Breast Cancer AJCC v8; Prognostic Stage IIIA Breast Cancer AJCC v8; Prognostic Stage IIIB Breast Cancer AJCC v8; Prognostic Stage IIIC Breast Cancer AJCC v8; Triple-Negative Breast Carcinoma

Outcome Measures

Primary Outcomes (1)

• Proportion of patients who have a CD8/FOXP3 ratio < 1.6 in their residual tumors after neoadjuvant chemotherapy (NAC) that convert to CD8/FOXP3 ratio >= 1.6

  A Simon optimum two stage phase II clinical trial design was chosen to test the null hypothesis that the rate of conversion to post-abemaciclib CD8/FOXP3 ratio of 1.6 or more is =\< 5% against the alternative that rate of conversion to post-abemaciclib CD8/FOXP3 ratio of 1.6 or more is \>= 20% with the target probability of a type I error and probability of a type II error set to 0.10. The probability of terminating after the first stage is 0.736, if the null hypothesis is true. A 90% confidence interval for this rate of conversion will be constructed using the Duffy-Santner approach taking into account the sequential nature of the study

  Up to 21 days

Secondary Outcomes (3)

• Incidence of adverse events

  Up to 60 days

• Changes in vimentin expression

  Up to 60 days

• Impact of length of treatment

  Up to 60 days

Other Outcomes (14)

• Changes in mitoses

  Up to 60 days

• Changes in nuclear pleomorphism

  Up to 60 days

• Changes in tubule formation

  Up to 60 days

Study Arms (2)

Cohort A Group 1; Cohort B Group 3 (surgery)

EXPERIMENTAL

Patients undergo standard of care surgical resection.

Procedure: Therapeutic Conventional Surgery

Cohort A Group 2; Cohort B Group 4 (abemaciclib, surgery)

EXPERIMENTAL

Patients receive abemaciclib PO BID on days 1-14 or days 1-21 in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgical resection no later than 12 weeks after the last dose of neoadjuvant chemotherapy.

Drug: Abemaciclib; Procedure: Therapeutic Conventional Surgery

Interventions

Abemaciclib DRUG

Given PO

Also known as: LY-2835219, LY2835219, Verzenio

Cohort A Group 2; Cohort B Group 4 (abemaciclib, surgery)

Therapeutic Conventional Surgery PROCEDURE

Undergo standard of care surgical resection

Cohort A Group 1; Cohort B Group 3 (surgery); Cohort A Group 2; Cohort B Group 4 (abemaciclib, surgery)

Eligibility Criteria

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

You may qualify if:

• Women of age \>=18 years
• PRE-REGISTRATION: Clinical T1-4, N0-3, M0 breast cancer at diagnosis (prior to the start of neoadjuvant chemotherapy) by American Joint Committee on Cancer (AJCC) staging version 8.
• Note: Benign breast disease, lobular carcinoma in situ (LCIS) or ductal carcinoma in situ (DCIS) in the ipsilateral or contralateral breast is allowed.
• Note: Additional ipsilateral or contralateral invasive breast cancer is allowed. The index lesion is the largest triple-negative, chemotherapy-resistant lesion.
• PRE-REGISTRATION: Histological confirmation of triple negative invasive breast cancer (defined as estrogen receptor \[ER\] =\< 10%, progesterone receptor \[PR\] =\< 10% and HER2 not amplified by in situ hybridization \[ISH\] or immunohistochemistry \[IHC\] 0/1) at diagnosis.
• PRE-REGISTRATION: Cohort A: CLOSED TO PRE-REGISTRATION and REGISTRATION as of protocol amendment 6 (04/14/2023) Neoadjuvant chemotherapy (NAC) with one of the following regimens that was not discontinued early due to intolerability with less than 50% of planned treatment given due to disease progression or patient request:
• Paclitaxel or docetaxel followed by one of the following: the combination of doxorubicin and cyclophosphamide (AC); the combination of epirubicin and cyclophosphamide (EC) or the combination of 5-fluorouracil, epirubicin and cyclophosphamide (FEC)
• Note: Carboplatin may be added to these regimens
• AC or EC or FEC followed by docetaxel or paclitaxel
• Note: Carboplatin may be added to these regimens
• Docetaxel in combination with doxorubicin and cyclophosphamide (TAC)
• Docetaxel in combination with cyclophosphamide (TC) (for patients who are not candidates for anthracyclines)
• Carboplatin or cisplatin in combination with a taxane (paclitaxel, docetaxel, or nab-paclitaxel) (for patients who are not candidates for anthracyclines)
• PRE-REGISTRATION: Cohort B: Neoadjuvant chemotherapy (NAC) with one of the following regimens in combination with pembrolizumab that was not discontinued early due to intolerability with less than 50% of planned treatment given due to disease progression or patient request:
• Paclitaxel or docetaxel followed by one of the following: the combination of doxorubicin and cyclophosphamide (AC); the combination of epirubicin and cyclophosphamide (EC) or the combination of 5-fluorouracil, epirubicin and cyclophosphamide (FEC) Note: Carboplatin may be added to these regimens

You may not qualify if:

• PRE-REGISTRATION: History of deep venous thrombosis (DVT) or pulmonary embolisms (PE) =\< 12 months prior to preregistration; OR Active DVT and/or PE requiring anti-coagulant therapy.
• NOTE: Patients who are on anti-coagulant therapy for maintenance are eligible as long as the DVT and/or PE was \> 12 months prior to enrollment and there is no evidence for active thrombosis (either DVT or PE).
• NOTE: Patients on anticoagulation are eligible; however peri-biopsy and peri-surgical management of anticoagulation is per the institutional standard of care.
• PRE-REGISTRATION: Prior treatment with CDK 4/6 inhibitors (e.g. palbociclib, ribociclib, abemaciclib, etc.)
• PRE-REGISTRATION: Prior treatment with radiation for this breast cancer.
• PRE-REGISTRATION: Prior incisional or excisional breast biopsy for this cancer.
• PRE-REGISTRATION: Any contraindications to pre-registration biopsy (such as bleeding diatheses, etc.).
• PRE-REGISTRATION: Receiving any investigational agent which would be considered as a treatment for the primary neoplasm.
• PRE-REGISTRATION: Other active malignancy =\< 3 years prior to registration.
• EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix.
• NOTE: If there is a history of prior malignancy, they must not be receiving another specific treatment for prior malignancy.
• PRE-REGISTRATION: Biopsy proven Stage IV breast cancer.
• PRE-REGISTRATION: Serious pre-existing medical conditions that would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment \[e.g., estimated creatinine clearance \< 30 ml/min\], 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).
• PRE-REGISTRATION: History of any of the following conditions:
• Syncope of cardiovascular etiology.

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (3)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Carcinoma, Intraductal, Noninfiltrating; Fibrocystic Breast Disease; Breast Carcinoma In Situ; Triple Negative Breast Neoplasms

Interventions

abemaciclib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Carcinoma in Situ; Neoplasms, Ductal, Lobular, and Medullary; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Neoplasms by Site

Study Officials

• Matthew P. Goetz, M.D.

  Mayo Clinic in Rochester

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: June 5, 2019
• First Posted: June 7, 2019
• Study Start: January 10, 2020
• Primary Completion: December 26, 2024
• Study Completion: December 26, 2024
• Last Updated: November 12, 2025

Record last verified: 2025-08

Locations

US (3)