A Trial of Niraparib in BAP1 and Other DNA Damage Response (DDR) Deficient Neoplasms (UF-STO-ETI-001)

NCT03207347 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: UF-STO-ETI-001IRB201701827 -AOCR15732
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 3

Brief Summary

This open-label, non-randomized study will investigate the use of niraparib in patients with tumors known to have mutations in BAP1 and other select DNA damage response pathway genes.

Conditions

Mesothelioma; Uveal Melanoma; Renal Cell Carcinoma; Cholangiocarcinoma

Keywords

BAP1; niraparib; DNA repair; PARP inhibitor; homologous repair deficiency; renal cell carcinoma; cholangiocarcinoma; mesothelioma; uveal melanoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Determine the objective response rate (ORR), which is defined as the percentage of subjects achieving a best overall response of partial or complete response (according to RECIST v1.1 criteria) from the start of the treatment until disease progression/recurrence or 30 days after the end of treatment, whichever occurs first. Per RECIST v1.1 criteria, a partial response is defined as a 30% or more decrease in the sum of the largest diameters of the target lesions. Per RECIST v1.1 criteria, a complete response is defined as the disappearance of target lesions (lymph nodes identified as lesions must have reduction in short axis to \<10 mm).

  1 year

Secondary Outcomes (4)

• Progression-Free Survival

  8 months

• Progression-Free Survival Rate at 3 Months

  3 months

• Progression-Free Survival Rate at 6 Months

  6 months

• Overall Survival

  10 months

Study Arms (2)

Cohort A

EXPERIMENTAL

This cohort will enroll patients with mesothelioma, uveal melanoma, renal cell carcinoma (clear cell type), and cholangiocarcinoma.

Drug: Niraparib

Cohort B

EXPERIMENTAL

This cohort will enroll patients whose tumors have a known DNA damage response mutation in any of the following genes: ARID1A, ATM, ATR, BACH1 (BRIP1), BAP1, BARD1, BLM, CHEK1, CHEK2, CDK2, CDK4, ERCC, FAM175A, FEN1, IDH1, IDH2, MRE11A, NBN (NBS1), PALB2, POLD1, PRKDC (DNA-PK) PTEN, RAD50, RAD51, RAD52, RAD54, RPA1, SLX4, WRN, or XRCC. This cohort is open to patients with any type of malignancy (except prostate).

Drug: Niraparib

Interventions

Niraparib DRUG

Patients will take 300 mg of niraparib orally once daily each day of a 28 day cycle.

Also known as: Zejula

Cohort A; Cohort B

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years
• Histologically confirmed clinical diagnosis of incurable cancer
• Confirmed diagnosis of uveal melanoma, mesothelioma, renal cell carcinoma (clear cell subtype), or cholangiocarcinoma (Cohort A only)
• Known DNA damage repair mutation including any one of the following: ARID1A, ATM, ATR, BACH1 (BRIP1), BAP1, BARD1, BLM, CHEK1, CHEK2, CDK2, CDK4, ERCC, FAM175A, FEN1, IDH1, IDH2, MRE11A, NBN (NBS1), PALB2, POLD1, PRKDC (DNA-PK) PTEN, RAD50, RAD51, RAD52, RAD54, RPA1, SLX4, WRN, or XRCC. Only CLIA certified next generation sequencing (NGS) assays are acceptable. Variants of unknown significance (VUS) will be allowed to enroll on study. (Cohort B only)
• Prior treatment with standard systemic therapy (must have exhausted or declined all known and currently approved effective life prolonging therapies)
• Must have formalin-fixed paraffin embedded (FFPE) tissue available for research purposes. Tissue must have been obtained within the last 3 years from a core or excisional biopsy.
• Measurable disease by RECIST (v 1.1) criteria
• Adequate organ function
• ECOG Performance Status of 0-1
• Life expectancy ≥ 12 weeks
• Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to the first dose AND be using an adequate method of contraception to avoid pregnancy throughout the study and for at least 180 days after the last dose of study drug to minimize the risk of pregnancy.
• Males with female partners of child-bearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 180 days following the last dose of study drug. In addition, men must not donate sperm during niraparib therapy and for 180 days after receiving the last dose of niraparib.
• Subjects must agree to not donate blood during the study or for 90 days after the last dose of study treatment.
• Subjects receiving oral corticosteroids may continue as long as their dose is stable for least 4 weeks prior to initiating protocol therapy.
• If a new biopsy is needed for diagnostic reasons, the biopsy must be performed from a tumor site that is not the only site of measurable disease.

You may not qualify if:

• Prior exposure to PARP inhibitors
• Subject has received or is planning to receive live vaccines within 30 days prior to the first dose of oral treatment and while participating in the trial
• Known BRCA1 or BRCA2 mutation
• Pathologic diagnosis of prostate cancer as the cancer to be treated in cohort B
• Simultaneous enrollment in any other interventional clinical trial
• Major surgery ≤ 3 weeks of study enrollment (Subject must have recovered from any effects of any major sugery.)
• Investigational therapy ≤ 4 weeks of first day of dosing of study drug
• Radiotherapy to \> 20% of the bone marrow within 4 weeks of the first dose of study drug
• Known hypersensitivity to the components of niraparib or the excipients
• Platelet or red blood cell transfusion ≤ 4 weeks of first dose of study drug
• Colony-stimulating factors within 4 weeks prior to starting protocol therapy
• More than one active malignancy at the time of enrollment (Subjects with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen \[as determined by the treatment physician and approved by the PI\] may be included).
• Known, active symptomatic brain or leptomeningeal metastases
• Subject has had any known Grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted \> 4 weeks and was related to the most recent treatment.
• Known history of myelodysplastic syndrome or acute myeloid leukemia

Sponsors & Collaborators

• University of Florida: lead
• GlaxoSmithKline: collaborator

Study Sites (3)

University of Florida

Gainesville, Florida, 32610, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Orlando Health UF Health Cancer Center

Orlando, Florida, 32806, United States

Location

Related Publications (1)

• George TJ, Lee JH, DeRemer DL, Hosein PJ, Staal S, Markham MJ, Jones D, Daily KC, Chatzkel JA, Ramnaraign BH, Close JL, Ezenwajiaku N, Murphy MC, Allegra CJ, Rogers S, Zhang Z, Li D, Srinivasan G, Shaheen M, Hromas R. Phase II Trial of the PARP Inhibitor, Niraparib, in BAP1 and Other DNA Damage Response Pathway-Deficient Neoplasms. JCO Precis Oncol. 2024 Dec;8:e2400406. doi: 10.1200/PO-24-00406. Epub 2024 Dec 3.

  PMID: 39626160 DERIVED

MeSH Terms

Conditions

Mesothelioma; Uveal Melanoma; Carcinoma, Renal Cell; Cholangiocarcinoma

Interventions

niraparib

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases; Adenocarcinoma; Carcinoma; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Allison Allegra
• Organization: University of Florida

allisonallegra3@ufl.edu

352-294-5691

Study Officials

• Thomas George, MD, FACP

  University of Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients in both cohorts will receive niraparib.

Study Record Dates

• First Submitted: June 26, 2017
• First Posted: July 2, 2017
• Study Start: August 13, 2018
• Primary Completion: August 30, 2022
• Study Completion: August 30, 2022
• Last Updated: September 15, 2023
• Results First Posted: September 15, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)