Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Antineoplastic Agents

All Drugs and Chemicals

Niraparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Patients receive niraparib PO QD on days 1-28. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Following completion of treatment, patients then undergo standard of care surgery.

Niraparib Tosylate Monohydrate

Radical Prostatectomy

Marc Dall'Era

This phase II trial studies how well niraparib, when given before surgery, works in treating patients with high risk prostate cancer that has not spread to other parts of the body (localized) and alterations in deoxyribonucleic acid (DNA) repair pathways. Niraparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To assess the impact of neoadjuvant niraparib tosylate monohydrate (niraparib) therapy prior to radical prostatectomy (RP) on pathologic tumor stage, frequency of lymph node metastases and positive margin rates for patients undergoing radical prostatectomy for high-risk, clinically localized prostate cancer with alterations in DNA repair pathways.

SECONDARY OBJECTIVE:

I. To assess 5-year biochemical recurrence in subjects with high-risk prostate cancer and DNA-damage response defects after prostatectomy.

OUTLINE:

Patients receive niraparib orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Following completion of treatment, patients then undergo standard of care surgery.

After completion of study treatment, patients are followed up at 30 days, every 3 months for 2 years, and then every 6 months for up to 3 years.

Niraparib Before Surgery in Treating Patients With High Risk Localized Prostate Cancer and DNA Damage Response Defects

Phase II Trial of PARP Inhibitor Niraparib for Men With High Risk Prostate Cancer and DNA Damage Response Defects

The study will assess the impact of neoadjuvant niraparib therapy prior to radical prostatectomy (RP) on pathologic tumor stage, frequency of lymph node metastases and positive margin rates for patients undergoing radical prostatectomy for high-risk, clinically localized prostate cancer with alterations in deoxyribonucleic acid (DNA) repair pathways. Pathologic complete response (PCR) defined as no tumor identified on hematoxylin and eosin (H\&E) stained sections will be assessed; minimal residual disease (MRD) will be defined as tumor clusters limited to \< 5 mm and confined to prostate gland.

Exact 95% confidence intervals for pRR and other binary outcomes, adjusted for the two-stage design, will be calculated as described by Koyama and Chen. Response rates will be compared between patients with biallelic and monoallelic loss using Fisher's Exact Test.

Median biochemical progression free survival (bPFS) and quartiles (when reached) will be calculated from Kaplan-Meier estimates, and 95% confidence intervals will be calculated using Greenwood's formula.

National Cancer Institute (NCI)

Janssen, LP

Marc Dall'Era, MD

Principal Investigator

Skin and Connective Tissue Diseases

Breast Neoplasms

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Breast Diseases

Skin Diseases

Hormones

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.

Abemaciclib

Alexandra Zimmer, M.D.

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.

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.

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

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

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 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.

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.

pCR will be tabulated as proportions and analyzed descriptively. Rate of delay to breast surgery will be summarized descriptively

RCB will be tabulated as proportions and analyzed descriptively. Rate of delay to breast surgery will be summarized descriptively

Defined as proportion of participants with time-to-surgery \> 90 days following completion of study therapy due to study-treatment related toxicity.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Niraparib Before Surgery in Treating Patients With High Risk Localized Prostate Cancer and DNA Damage Response Defects	NCT04030559	ATM Gene Mutati... BRCA1 Gene Muta... BRCA2 Gene Muta... BRIP1 Gene Muta... CDK12 Gene Muta... CHEK1 Gene Muta... CHEK2 Gene Muta... DNA Damage Resp... DNA Repair Gene... FANCA Gene Muta... FANCD2 Gene Mut... FANCL Gene Muta... GEN1 Gene Mutat... NBN Gene Mutati... Prostate Carcin... RAD51 Gene Muta... RAD51C Gene Mut...	Niraparib Niraparib Tosyl... Radical Prostat...	18 Years -	University of California, Davis
Abemaciclib and Niraparib Before Surgery for the Treatment of Hormone Receptor Positive HER2 Negative Breast Cancer	NCT04481113	Anatomic Stage ... Anatomic Stage ... Anatomic Stage ... Anatomic Stage ... Anatomic Stage ... Anatomic Stage ... Anatomic Stage ... HER2 Negative B... Hormone Recepto... Invasive Breast... Multifocal Brea... Prognostic Stag... Prognostic Stag... Prognostic Stag... Prognostic Stag... Prognostic Stag... Prognostic Stag... Prognostic Stag... Prognostic Stag... Unilateral Brea...	Abemaciclib Niraparib Tosyl...	18 Years -	OHSU Knight Cancer Institute
Niraparib Before Surgery in Treating Patients With High Risk Localized Prostate Cancer and DNA Damage Response Defects	NCT04030559	ATM Gene Mutati... BRCA1 Gene Muta... BRCA2 Gene Muta... BRIP1 Gene Muta... CDK12 Gene Muta... CHEK1 Gene Muta... CHEK2 Gene Muta... DNA Damage Resp... DNA Repair Gene... FANCA Gene Muta... FANCD2 Gene Mut... FANCL Gene Muta... GEN1 Gene Mutat... NBN Gene Mutati... Prostate Carcin... RAD51 Gene Muta... RAD51C Gene Mut...	Niraparib Niraparib Tosyl... Radical Prostat...	18 Years -	University of California, Davis

Spots Global Cancer Trial Database for niraparib tosylate monohydrate