NCT04481113

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

A Phase 1 Study of Abemaciclib and Niraparib as Neoadjuvant Therapy in Hormone Receptor Positive (HR+) HER2 Negative (HER2-) Breast Cancer

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 8 (actual)
• Sponsor: OHSU Knight Cancer Institute · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

PRIMARY OBJECTIVES: I. To determine the maximum-tolerated dose (MTD) and/or recommended phase 2 dose of the combination of abemaciclib and niraparib tosylate monohydrate (niraparib). II. To assess safety and tolerability of the combination of abemaciclib and niraparib in early stage HR+ breast cancer. SECONDARY OBJECTIVES: I. To determine clinical response to treatment. II. To determine pathologic response to treatment. III. To determine feasibility of combination as determined by no delay to standard of care breast surgery. EXPLORATORY OBJECTIVE: I. To assess occurrence of secondary myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) malignancy. OUTLINE: This is a phase 1 dose-escalation study of abemaciclib in combination with niraparib followed by a dose-expansion study. Patients receive abemaciclib orally (PO) twice daily (BID) and niraparib PO once daily (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. Patients are followed up at 30 days after date of surgery, every 3 months for the first 6 months, every 6 months for 2 years, then annually for up to 5 years from date of surgery.

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

Interventions

Type	Name	Description
DRUG	Abemaciclib	Given PO
DRUG	Niraparib Tosylate Monohydrate	Given PO

Timeline

• Start date: 2021-06-07
• Primary completion: 2023-10-11
• Completion: 2025-06-20
• First posted: 2020-07-22
• Last updated: 2026-01-29

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study