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

Symptoms and General Pathology

Respiratory Tract (Lung and Bronchial) Diseases

Recurrence

Lung Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Talazoparib

Patients receive talazoparib PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis

Pharmacological Study

Vassiliki Papadimitrakopoulou

This phase II trial studies how well talazoparib works in treating patients with homologous recombination repair deficiency (HRRD) positive stage IV squamous cell lung cancer that has come back after previous treatment. Talazoparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To evaluate the overall response rate (ORR) (confirmed and unconfirmed, complete and partial) with talazoparib (BMN 673) in HRRD Medivation (MDVN)-positive patients.

SECONDARY OBJECTIVES:

I. To evaluate investigator assessed progression-free survival (IA-PFS) and overall survival (OS) associated with therapy in HRRD MDVN-positive patients.

II. To evaluate ORR, IA-PFS, and OS in HRRD Foundation Medicine, Inc. (FMI)-positive patients.

III. To evaluate ORR in HRRD MDVN-negative/HRRD FMI-positive patients. IV. To evaluate the frequency and severity of toxicities associated with talazoparib (BMN 673) in HRRD FMI-positive patients.

TERTIARY OBJECTIVES:

I. To assess if the homologous recombination deficiency (HRD) score is associated with clinical outcomes (response, PFS, OS) in HRRD FMI-positive patients treated with talazoparib (BMN 673).

II. To assess if the level of PARP protein expression determined by immunohistochemistry is associated with clinical outcomes (response, PFS, OS) in HRRD FMI-positive patients treated with talazoparib (BMN 673).

III. To characterize pharmacokinetic properties of talazoparib (BMN 673).

OUTLINE:

Patients receive talazoparib orally (PO) once daily (QD) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 6 months for 2 years, and at the end of year 3.

Lung-MAP: Talazoparib in Treating Patients With HRRD Positive Recurrent Stage IV Squamous Cell Lung Cancer

A Phase II Study of Talazoparib (BMN 673) in Patients With Homologous Recombination Repair Deficiency Positive Stage IV Squamous Cell Lung Cancer (Lung-Map Sub-Study)

A logistic regression model will be used as both a continuous variable and categorized as high versus low. A Cox regression model will be used to assess associations with progression free survival and overall survival.

A logistic regression model will be used to evaluate if HRD score (as both a continuous variable and categorized as high versus low) and PARP protein expression levels are associated with response. Similarly, a Cox regression model will be used to assess associations with progression free survival and overall survival.

The percentage of participants with confirmed and unconfirmed, partial response and complete response to treatment with talazoparib per Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Analysis was performed using a more restricted definition of homologous recombination repair deficiency (HRRD)-positivity (Medivation \[MDVN\] criteria; defined by alterations in ATM/ATR/BRCA1/BRCA2/PALB2 genes). With 40 HRRD subset positive patients, overall response rate can be estimated within 13% with 95% confidence.

From date of sub-study registration to date of first documentation of progression assessed by local review or symptomatic deterioration or death due to any cause. Participants last known to be alive without report of progression were censored at date of last disease assessment.

Analysis was performed using a more restricted definition of homologous recombination repair deficiency (HRRD)-positivity (Medivation \[MDVN\] criteria; defined by alterations in ATM/ATR/BRCA1/BRCA2/PALB2 genes).

From date of sub-study registration to date of death due to any cause. Participants last known to be alive were censored at date of last contact.

Analysis was performed using a more restricted definition of homologous recombination repair deficiency (HRRD)-positivity (Medivation \[MDVN\] criteria; defined by alterations in ATM/ATR/BRCA1/BRCA2/PALB2 genes).

The percentage of participants with confirmed and unconfirmed, partial response and complete response to treatment with talazoparib per Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Analysis was performed using a broader definition of homologous recombination repair deficiency (HRRD)-positivity (Foundation Medicine Inc. \[FMI\] criteria; defined by alterations in ATM/ATR/BARD1/BRCA1/BRCA2/BRIP1/CHEK1/CHEK2/FANCA/FANCC/FANCD2/FANCF/FANCM/NBN(NBS1)/PALB2/RAD51/RAD51B(RAD51L1)/RAD54L/RPA1 genes).

From date of sub-study registration to date of first documentation of progression assessed by local review or symptomatic deterioration or death due to any cause. Participants last known to be alive without report of progression were censored at date of last disease assessment.

Analysis was performed using a broader definition of homologous recombination repair deficiency (HRRD)-positivity (Foundation Medicine Inc. \[FMI\] criteria; defined by alterations in ATM/ATR/BARD1/BRCA1/BRCA2/BRIP1/CHEK1/CHEK2/FANCA/FANCC/FANCD2/FANCF/FANCM/NBN(NBS1)/PALB2/RAD51/RAD51B(RAD51L1)/RAD54L/RPA1 genes).

From date of sub-study registration to date of death due to any cause. Participants last known to be alive were censored at date of last contact.

Analysis was performed using a broad definition of homologous recombination repair deficiency (HRRD)-positivity (Foundation Medicine Inc. \[FMI\] criteria; defined by alterations in ATM/ATR/BARD1/BRCA1/BRCA2/BRIP1/CHEK1/CHEK2/FANCA/FANCC/FANCD2/FANCF/FANCM/NBN(NBS1)/PALB2/RAD51/RAD51B(RAD51L1)/RAD54L/RPA1 genes).

From date of documentation of response (complete or partial) to date of first documentation of progression assessed by local review or symptomatic deterioration or death due to any cause among participants who achieve a complete or partial response.

The percentage of participants with confirmed and unconfirmed, partial response and complete response to treatment with talazoparib per Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Analysis was performed on participants that meet a broader definition of homologous recombination repair deficiency (HRRD)-positivity (Foundation Medicine Inc.) but not the stricter definition set by MDVN.

\[FMI\] criteria; defined by alterations in ATM/ATR/BARD1/BRCA1/BRCA2/BRIP1/CHEK1/CHEK2/FANCA/FANCC/FANCD2/FANCF/FANCM/NBN(NBS1)/PALB2/RAD51/RAD51B(RAD51L1)/RAD54L/RPA1 genes).

Adverse Events (AEs) are reported by CTCAE Version 4.0. Only adverse events that are possibly, probably or definitely related to study drug are reported.

SWOG Cancer Research Network

47 participants that were eligible and received protocol therapy were assessed for AEs

Participants receive talazoparib PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis: Correlative studies

Pharmacological Study: Correlative studies

Talazoparib: Given PO

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Measure Description: Participants were graded according to the Zubrod Performance Status Scale.

0 - Fully active, able to carry out on all pre-disease performance without restriction.

1 - Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g. light housework, office work.

Performance status

Number of prior lines of therapy for stage IV disease

Current smoker

Recent smoker

Former smoker

Never smoker

Smoking status

Lung Committee Statistician

Participants that meet the MDVN criteria for homologous recombination repair deficiency (HRRD)

Overall Response Rate Assessed by Response Evaluation Criteria in Solid Tumors 1.1 in HRRD-positive (MDVN) Participants

Eligible participants that meet the MDVN criteria for homologous recombination repair deficiency (HRRD)

Investigator-assessed Progression-free Survival (IA-PFS) in HRRD-positive (MDVN) Participants

Overall Survival (OS) in HRRD-positive (MDVN) Participants

All eligible participants that meet a broad definition of homologous recombination repair deficiency (HRRD) -positivity (Foundation Medicine Inc. \[FMI\] criteria).

Overall Response Rate Assessed by Response Evaluation Criteria in Solid Tumors 1.1 in HRRD-positive (FMI) Participants

All eligible participants that meet the FMI criteria for homologous recombination repair deficiency (HRRD)

Investigator-assessed Progression Free Survival (IA-PFS) FEP in HRRD-positive (FMI) Participants

Overall Survival (OS) in HRRD-positive (FMI) Participants

Duration of Response in HRRD-positive (FMI) Participants

All eligible participants that meet a broad definition of homologous recombination repair deficiency (HRRD)-positivity (Foundation Medicine Inc. \[FMI\] criteria), but do not meet the more restrictive MDVN criteria for HRRD positivity.

Overall Response Rate Assessed by Response Evaluation Criteria in Solid Tumors 1.1 in HRRD-negative Per MDVN But HRRD-positive Per FMI Participants

Alanine aminotransferase increased

Anemia

Aspartate aminotransferase increased

Dehydration

Dyspnea

Fatigue

Generalized muscle weakness

Hypertension

Hypoalbuminemia

Hyponatremia

Hypotension

Hypoxia

Lung infection

Lymphocyte count decreased

Nausea

Neutrophil count decreased

Platelet count decreased

Respiratory failure

Sepsis

Vomiting

White blood cell decreased

Wound infection

Participants who received at least one dose of talazoparib treatment.

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
Lung-MAP: Talazoparib in Treating Patients With HRRD Positive Recurrent Stage IV Squamous Cell Lung Cancer	NCT03377556	ATM Gene Mutati... ATR Gene Mutati... BARD1 Gene Muta... BRCA1 Gene Muta... BRCA2 Gene Muta... BRIP1 Gene Muta... CHEK1 Gene Muta... CHEK2 Gene Muta... FANCA Gene Muta... FANCC Gene Muta... FANCD2 Gene Mut... FANCF Gene Muta... FANCM Gene Muta... NBN Gene Mutati... PALB2 Gene Muta... RAD51 Gene Muta... RAD51B Gene Mut... RAD54L Gene Mut... Recurrent Squam... RPA1 Gene Mutat... Stage IV Squamo...	Laboratory Biom... Pharmacological... Talazoparib	-	SWOG Cancer Research Network
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

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