Neo-Adjuvant Abemaciclib With Fulvestrant in Patients With ER/PR +HER Negative Breast Cancer

NCT04305236 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: UCI 18-79 [HS# 2020-5660]2020-5660
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 2 single-arm, open-label determining efficacy of Neo-adjuvant Abemaciclib and Fulvestrant in subjects with Hormone receptor positive patients with localized non-metastatic breast cancer who develop local recurrence while on adjuvant endocrine therapy with molecular evidence of endocrine resistance.

Conditions

Breast Neoplasm; Hormone Receptor Positive Breast Carcinoma

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With a Pathological Complete Response

  This is defined as the percentage of subjects who achieve a pathological complete response (pCR). A pCR is defined by no evidence of tumor cells in the final surgical specimen.

  From start of study treatment to surgery, on average we expect 6 months.

Secondary Outcomes (6)

• Overall Response Rate

  From start of study treatment to surgery, on average we expect 6 months.

• Percentage of Participants Who Undergo Breast Conserving Surgery

  From start of study treatment to surgery, on average we expect 6 months.

• Recurrence Disease Free Survival

  Up to 5 years

• Percentage of Grade 3-5 Adverse Events

  From start of study treatment to surgery, on average we expect 6 months.

• Percentage Change in Ki 67

  From start of study treatment to surgery, on average we expect 6 months.

Study Arms (1)

Abemaciclib and Fulvestrant

EXPERIMENTAL

Abemaciclib will be administered orally at the dose of 150 mg twice daily. Fulvestrant will be administered intramuscularly at an initial loading dose of 500mg on days 1 and 15 of the first cycle and then 500 mg intramuscularly every first day of each subsequent cycle. One cycle is 28 days.

Drug: Abemaciclib; Drug: Fulvestrant

Interventions

Abemaciclib DRUG

Given PO

Also known as: VERZENIO™

Abemaciclib and Fulvestrant

Fulvestrant DRUG

Given Intramuscularly

Also known as: FASLODEX®

Abemaciclib and Fulvestrant

Eligibility Criteria

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

You may qualify if:

• Patients must have a diagnosis of HR+ breast cancer. To fulfill the requirement of HR+ disease, a breast cancer must express, by immunohistochemistry (IHC), at least one of the hormone receptors (ER, progesterone receptor \[PgR\]) as defined in the relevant American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) Guidelines (Hammond et al. 2010):
• \. For ER and PgR assays to be considered positive, ≥1% of tumor cell nuclei must be immunoreactive by immunohistochemistry (IHC) (Hammond et al. 2010).
• Patients must have Loco regional breast cancer (Stage I, Stage II and stage III per AJCC 8th edition criteria for staging of breast cancer)
• Patients must have localized recurrence while on adjuvant endocrine therapy
• Patients must have any known molecular evidence of endocrine resistance by next generation sequencing
• Age ≥ 18 years.
• ECOG performance status 0-1
• Have post-menopausal status as defined by following:
• Prior bilateral oophorectomy
• Age ≥ 60 years
• Age \< 60 and amenorrheic (non-treatment-induced amenorrhea secondary to tamoxifen, toremifene, ovarian suppression, or chemotherapy) for at least 12 months. Follicle-stimulating hormone (FSH) and estradiol must be in the postmenopausal range.
• Have at least one measurable disease as defined per RECIST 1.1
• Adequate organ and marrow function as defined below:
• Hemoglobin\* \> 8 g/dL
• Absolute neutrophil count ≥ 1,500/mcL

You may not qualify if:

• Stage IV metastatic breast cancer
• \. This study will utilize the American Joint Committee on Cancer (AJCC) staging system, eight edition that provides a strategy for grouping patients with respect to prognosis. The AJCC has designated staging by TNM classification. The researchers will also review tumor size, lymph node status, and estrogen-receptor and progesterone-receptor levels in the tumor tissue.
• Patients with HER2 positive and triple negative breast cancer
• \. To fulfill the requirement of HER2- and Triple negative disease, a breast cancer must not demonstrate, at initial diagnosis or upon subsequent biopsy, overexpression of HER2 or should not express ER or PR receptors by either IHC or in-situ hybridization (ISH) as defined in the relevant ASCO/CAP guidelines (Wolff et al. 2013).
• Inflammatory breast cancer
• Newly diagnosed endocrine naïve patients
• No molecular evidence of endocrine resistance
• Prior treatment with any CDK 4/6 inhibitor and/or Fulvestrant
• Pre-menopausal women
• Are currently receiving an investigational drug in a clinical trial or participating in any other type of medical research judged not to be scientifically or medically compatible with this study. If a patient is currently enrolled in a clinical trial involving non-approved use of a device, then agreement with the principal investigator is required to establish eligibility
• Have had major surgery within 14 days prior to enrollment to allow for post-operative healing of the surgical wound
• Have initiated bisphosphonates or approved RANK ligand therapy for breast cancer with osseous metastasis, if patients are received Zolendronic acid or Denosumab in the adjuvant manner then such patients will be allowed participate
• Have serious preexisting medical conditions that, in the judgment of the investigator, would preclude participation in this study (for example, history of major surgical resection involving the stomach or small bowel or preexisting Crohn's disease or ulcerative colitis , interstitial lung disease, severe dyspnea at rest, any pre-existing chronic condition resulting in baseline grade 2 or higher diarrhea)
• Have a personal history of any of the following conditions: syncope or cardiovascular etiology, ventricular tachycardia, ventricular fibrillation or sudden cardiac arrest
• Have a history of any other cancer (except for non-melanoma skin cancer or carcinoma in situ of the cervix) unless in complete remission with no therapy for a minimum of three years or have received an autologous or allogeneic stem-cell transplant

Sponsors & Collaborators

• University of California, Irvine: lead
• Eli Lilly and Company: collaborator

Study Sites (1)

Chao Family Comprehensive Cancer Center, University of California, Irvine

Orange, California, 92868, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

abemaciclib; Fulvestrant

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Limitations and Caveats

Early study termination and depleted funding lead to the small number of patients enrolled onto the study. This also contributed to the inability to analyze the primary and secondary objectives.

Results Point of Contact

• Title: UC Irvine Health / Chao Family Comprehensive Cancer Center
• Organization: UC Irvine Health / Chao Family Comprehensive Cancer Center

ucstudy@uci.edu

1-877-UC-STUDY

Study Officials

• Ritesh Parajuli, MD

  Chao Family Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: Assistant Clinical Professor

Study Record Dates

• First Submitted: March 9, 2020
• First Posted: March 12, 2020
• Study Start: July 23, 2020
• Primary Completion: February 16, 2022
• Study Completion: February 16, 2022
• Last Updated: June 6, 2023
• Results First Posted: March 3, 2023

Record last verified: 2023-05

Locations

US (1)