Abemaciclib and Niraparib Before Surgery for the Treatment of Hormone Receptor Positive HER2 Negative Breast Cancer

NCT04481113 | Completed Phase 1 FDA Drug

• 2 other identifiers: STUDY00021243NCI-2020-03813
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial tests the side effects and best dose of abemaciclib and niraparib in treating patients with breast cancer that is positive for estrogen or progesterone receptors (hormone receptor positive \[HR+\]) and HER2 negative. Abemaciclib may stop the growth of tumor cells by blocking certain proteins called cyclin-dependent kinases, which are needed for cell growth. PARPs are proteins that help repair DNA mutations. PARP inhibitors, such as niraparib, can keep PARP from working so tumor cells can't repair themselves and grow. Giving abemaciclib and niraparib together before surgery may make the tumor smaller.

Conditions

Anatomic Stage I Breast Cancer AJCC v8; Anatomic Stage IA Breast Cancer AJCC v8; Anatomic Stage IB Breast Cancer AJCC v8; Anatomic Stage II Breast Cancer AJCC v8; Anatomic Stage IIA Breast Cancer AJCC v8; Anatomic Stage IIB Breast Cancer AJCC v8; Anatomic Stage IIIA Breast Cancer AJCC v8; HER2 Negative Breast Adenocarcinoma; Hormone Receptor Positive Breast Adenocarcinoma; Invasive Breast Carcinoma; Multifocal 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 IIIA Breast Cancer AJCC v8; Prognostic Stage IIIB Breast Cancer AJCC v8; Unilateral Breast Carcinoma

Outcome Measures

Primary Outcomes (2)

• Incidence of dose limiting toxicities (DLTs) for the proposed combination

  Dose-limiting toxicities will specifically be reported for the DLT evaluation period using the MTD-evaluable population.

  First dose of study agents to end of cycle 1 for dose-determining phase (each cycle is 28 days)

• Incidence of adverse events (AEs) and serious AEs for the proposed combination

  Adverse events will be tabulated by the Medical Dictionary for Regulatory Activities (MedDRA version 21.1) preferred term and system organ class and a preferred term. The severity of the AEs will be assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 criteria. Descriptive statistics using the safety evaluable population will be used to report on all on-study AEs, grade 3-4 AEs, treatment-related AEs, grade 3-4 treatment-related AEs, serious adverse events (SAEs), treatment-related SAEs, and AEs leading to discontinuation per CTCAE v5.0. Grade 3-4 laboratory abnormalities will be summarized using worst grade NCI CTCAE v 5.0 criteria.

  Up to 90 days from last dose of study agent (up to 7 months)

Secondary Outcomes (5)

• Overall objective response rate (ORR)

  From the date of first dose of study agents to 30 days post-surgery (up to 5 months)

• Clinical benefit rate (CBR)

  From date of dose of study agents to 30 days post-surgery (up to 5 months)

• Rate of pathological complete response (pCR)

  At time of surgical resection (up to 4 months)

• Rate of residual cancer burden (RCB) 0-1

  At time of surgical resection (up to 4 months)

• Rate of delay to breast surgery

  From date of last dose of study drug to date of surgery (up to 4 months)

Other Outcomes (1)

• Incidence of myelodysplastic syndrome/acute myeloid leukemia

  Up to 5 years from the last dose of study drugs

Study Arms (1)

Treatment (abemaciclib, niraparib)

EXPERIMENTAL

Patients receive abemaciclib PO BID and niraparib PO QD. Treatment repeats every 28 days for up to 2-4 cycles in the absence of disease progression or unacceptable toxicity. Patients who complete 4 cycles undergo standard of care mastectomy or lumpectomy. Patients demonstrating progressive disease after only 2 cycles are switched to receive standard of care chemotherapy prior to undergoing mastectomy or lumpectomy.

Drug: Abemaciclib; Drug: Niraparib Tosylate Monohydrate

Interventions

Abemaciclib DRUG

Given PO

Also known as: LY-2835219, LY2835219, Verzenio

Treatment (abemaciclib, niraparib)

Niraparib Tosylate Monohydrate DRUG

Given PO

Also known as: Zejula

Treatment (abemaciclib, niraparib)

Eligibility Criteria

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

You may qualify if:

• Ability to understand and the willingness to sign a written informed consent document.
• Females (regardless of menopausal status), or males
• Biopsy proven estrogen receptor (ER) and/or progesterone receptor (PR) positive as defined as ER \>= 1% and/or PR \>= 1% by immunohistochemistry according to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines for hormone receptor testing
• HER2 non-amplified per 2018 ASCO/CAP guidelines, defined as:
• Immunohistochemistry (IHC) score 0/1+, or
• IHC 2+ and in situ hybridization (ISH) non-amplified with a ratio of HER2 to CEP17 \< 2.0, and if reported, average HER2 gene copy number \< 4 signals/cells; or
• ISH non-amplified with a ratio of HER2 to CEP17 \< 2.0, and if reported, average HER2 gene copy number \< 4 signals/cells
• Clinical T1-T3, any N, M0 invasive breast cancer, by American Joint Committee on Cancer (AJCC) 8th edition clinical staging with the goal being curative intent surgery to completely excise involved tumor in the breast and the draining lymph nodes
• Individuals with unilateral, multi-focal breast cancer (defined as more than one lesion of invasive breast cancer in the same breast separated from the dominant breast lesion by less than 5 cm of radiologically normal breast tissue) are eligible
• Participants must be planned for neoadjuvant chemotherapy
• Except for allowable endocrine therapy up to 4 weeks prior to study enrollment, participants must not have received prior anti-cancer therapy for the treatment of their breast cancer
• Participant must have disease that is amenable to biopsy, and agree to provide the required research biopsies at baseline, and 2 months after initiating study therapy
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
• The participant is able to swallow oral medications
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L

You may not qualify if:

• Prior history of malignancy within 5 years except for successfully treated cervical carcinoma in situ, lobular carcinoma in situ of the breast, or non-melanoma skin cancer
• Inflammatory breast cancer defined as clinically significant erythema of the breast and/or documented dermal lymphatic invasion (not direct skin invasion by tumor or peau d'orange without erythema) is not eligible
• Participants that have undergone surgical axillary staging procedure prior to study entry
• Fine needle aspiration (FNA) or core needle biopsy of axillary node is permitted
• Bilateral breast cancer, except for those tumors exhibiting similar biomarkers (grade, ER/PR, HER2)
• Clinical or radiographic evidence of metastatic disease
• Isolated ipsilateral supraclavicular node involvement is permitted
• A prior history of ductal breast carcinoma in situ (DCIS) treated with contralateral mastectomy and not receiving endocrine therapy is eligible
• Breast implants are contraindicated only if the implant precludes the required research biopsies or interferes with palpating the breast lesion
• Prior treatment for this cancer including surgery, radiation therapy, chemotherapy, biotherapy, hormonal therapy or investigational agent prior to study entry
• Participants may have received up to 4 weeks of endocrine therapy prior to enrollment on trial
• Participants with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)
• Contraindication to undergoing breast and/or axillary lymph node biopsy
• Contraindication to undergoing surgical resection
• Prior therapy with a PARP inhibitor

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• Eli Lilly and Company: collaborator
• GlaxoSmithKline: collaborator
• Oregon Health and Science University: collaborator

Study Sites (1)

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

MeSH Terms

Conditions

Unilateral Breast Neoplasms

Interventions

abemaciclib; niraparib

Condition Hierarchy (Ancestors)

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

Study Officials

• Alexandra Zimmer, M.D.

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 17, 2020
• First Posted: July 22, 2020
• Study Start: June 7, 2021
• Primary Completion: October 11, 2023
• Study Completion: June 20, 2025
• Last Updated: January 29, 2026

Record last verified: 2025-04

Locations

US (1)