Abemaciclib and Niraparib Before Surgery for the Treatment of Hormone Receptor Positive HER2 Negative Breast Cancer
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04481113|
Recruitment Status : Not yet recruiting
First Posted : July 22, 2020
Last Update Posted : October 19, 2020
|Condition or disease||Intervention/treatment||Phase|
|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 Hormone Receptor Positive Breast Carcinoma 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 HER2 Negative Breast Carcinoma||Drug: Abemaciclib Drug: Niraparib Tosylate Monohydrate||Phase 1|
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.
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.
OUTLINE: This is a phase 1 dose-escalation study of abemaciclib in combination with niraparib.
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||25 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1 Study of Abemaciclib and Niraparib as Neoadjuvant Therapy in Hormone Receptor Positive (HR+) HER2 Negative (HER2-) Breast Cancer|
|Estimated Study Start Date :||January 13, 2021|
|Estimated Primary Completion Date :||December 31, 2021|
|Estimated Study Completion Date :||December 30, 2022|
Experimental: Treatment (abemaciclib, niraparib)
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: Niraparib Tosylate Monohydrate
Other Name: Zejula
- Incidence of dose limiting toxicities (DLTs) for the proposed combination [ Time Frame: Date of enrollment to 30 days from last dose of study agents ]Dose-limiting toxicities will specifically be reported for the DLT evaluation period using the MTD-evaluable population.
- Incidence of adverse events (AEs) and serious AEs for the proposed combination [ Time Frame: Up to 4 cycles (each cycle is 28 days) ]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.
- Overall objective response rate (ORR) [ Time Frame: From the date of first dose of study agents to 30 days post-surgery ]Overall response will be summarized descriptively. ORR will be estimated with 95% confidence interval (CI). The CI will be calculated based on the exact method for binomial distributions.
- Clinical benefit rate (CBR) [ Time Frame: From date of dose of study agents to 30 days post-surgery ]An estimate of CBR will be measured and reported with 95% exact CI. Participants who achieve a complete response (CR), partial response (PR), or stable disease (SD) for at least 6 months on the current protocol will be qualified as deriving benefit from therapy and will count towards the CBR measurement.
- Rate of pathological complete response (pCR) [ Time Frame: Intraoperative (At time of surgical resection) ]pCR will be tabulated as proportions and analyzed descriptively. Rate of delay to breast surgery will be summarized descriptively
- Rate of residual cancer burden (RCB) 0-1 [ Time Frame: Intraoperative (At time of surgical resection) ]RCB will be tabulated as proportions and analyzed descriptively. Rate of delay to breast surgery will be summarized descriptively
- Rate of delay to breast surgery [ Time Frame: From date of last dose of study drug to date of surgery (up to 4 months) ]Defined as proportion of participants with time-to-surgery > 90 days following completion of study therapy due to study-treatment related toxicity.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04481113
|United States, Oregon|
|OHSU Knight Cancer Institute|
|Portland, Oregon, United States, 97239|
|Contact: Zahi Mitri, MD, MS 503-494-9160 firstname.lastname@example.org|
|Principal Investigator: Zahi Mitri, MD, MS|
|Principal Investigator:||Zahi Mitri, MD, MS||OHSU Knight Cancer Institute|