MesotheliomaPhase 2NCT03207347
A Trial of Niraparib in BAP1 and Other DNA Damage Response (DDR) Deficient Neoplasms (UF-STO-ETI-001)
A Phase 2 study testing Niraparib in people with Mesothelioma and Uveal Melanoma, run by University of Florida at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Mesothelioma, Uveal Melanoma, Renal Cell Carcinoma
- What is being tested?
- Niraparib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 3 sitesUnited States
- Study dates
- 13 Aug 2018to 30 Aug 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.)
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- 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
- Females or males of childbearing potential who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period and for at least 180 days after the last dose of study drug.
- Females who are pregnant or breastfeeding
- History of any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of protocol therapy or that might affect the interpretation of the results of the study or that puts the subject at high risk for treatment complications, in the opinion of the treating physician or study PI.
- Prisoners or subjects who are involuntarily incarcerated.
- Subjects who are compulsorily detained for treatment of either a psychiatric or physical illness.
- Subjects demonstrating an inability to comply with the study and/or follow-up procedures
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of Florida
Gainesville, Florida, 32610
University of Miami
Miami, Florida, 33136
Orlando Health UF Health Cancer Center
Orlando, Florida, 32806
About this study
Official title: A Phase II Trial of the PARP Inhibitor, Niraparib, in BAP1 and Other DNA Damage Response (DDR) Pathway Deficient Neoplasms (UF-STO-ETI-001)
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.
Read the detailed description
BAP1 is an ubiquitin ligase that is critical in helping to regulate the cell cycle, cellular differentiation, and cell death. This protein is also intimately involved with DNA double-strand break repair. Germline mutations in the BAP1 gene are associated with a hereditary cancer syndrome that increases the risk of uveal melanoma, mesothelioma and renal cell carcinoma. PARP is another protein that is crucial in DNA repair and enables continued cell replication and survival. It is hypothesized that PARP inhibition with niraparib will result in significant cytoreduction in patient tumors with mutations in BAP1 and other components of the DNA damage response pathway through synthetic lethality. Synthetic lethality is the inhibition of a gene that a cell relies on to compensate for the loss of another gene, resulting in the cell's demise.
- Conditions
- Mesothelioma, Uveal Melanoma, Renal Cell Carcinoma, Cholangiocarcinoma
- Being tested
- Niraparib
- Keywords
- BAP1, niraparib, DNA repair, PARP inhibitor, homologous repair deficiency, renal cell carcinoma, cholangiocarcinoma, mesothelioma, uveal melanoma
- Medical subject headings
- Mesothelioma, Uveal Melanoma, Carcinoma, Renal Cell, Cholangiocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NiraparibDrug
Also called Zejula
Patients will take 300 mg of niraparib orally once daily each day of a 28 day cycle.
| Study group | Role | What they receive |
|---|---|---|
| Cohort A | Experimental | This cohort will enroll patients with mesothelioma, uveal melanoma, renal cell carcinoma (clear cell type), and cholangiocarcinoma. Receives: 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). Receives: Drug: Niraparib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 1 year
Secondary outcomes (4)
Progression-Free Survival
Determine the median progression-free survival. Progression-free survival is defined as the duration of time from study entry to time of progression or death or the date of last contact, whichever occurs first. Progression is defined by RECIST v1.1 criteria and is defined as an increase of at least 20% in the sum of the largest diameters of target lesions and/or the appearance of new lesions.
Measured: 8 months
Progression-Free Survival Rate at 3 Months
Determine the progression-free survival rate at 3 months after study entry in each cohort. This is the percentage of subjects that both have not had disease progression and are alive 3 months after study entry. Disease progression is defined by RECIST v1.1 criteria and is defined as an increase of at least 20% in the sum of the largest diameters of target lesions and/or the appearance of new lesions.
Measured: 3 months
Progression-Free Survival Rate at 6 Months
Determine the progression-free survival rate at 6 months after study entry in each cohort. This is the percentage of subjects that both have not had disease progression and are alive 6 months after study entry. Progression is defined by RECIST v1.1 criteria and is defined as an increase of at least 20% in the sum of the largest diameters of target lesions and/or the appearance of new lesions.
Measured: 6 months
Overall Survival
Estimate the median overall survival. Overall survival is defined as the duration of time from date of study entry until date of death or date of last contact.
Measured: 10 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2017
- Study start13 Aug 2018
- Primary completion30 Aug 2022
- Study completion30 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MesotheliomaStudies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Patients in both cohorts will receive niraparib.
- Masking
- None (open label)
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- Thomas George, MD, FACP, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03207347
- Sponsor's protocol ID
- UF-STO-ETI-001
- Other IDs
- IRB201701827 -A, OCR15732
- Status last verified
- Sep 2023
- First submitted
- 26 Jun 2017
- Last updated
- 15 Sep 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 39626160
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of the PARP Inhibitor, Niraparib, in BAP1 and Other DNA Damage Response (DDR) Pathway Deficient Neoplasms (UF-STO-ETI-001)
- ClinicalTrials.gov ID
- NCT03207347
- Acronym / sponsor ID
- UF-STO-ETI-001
- Conditions
- Mesothelioma, Uveal Melanoma, Renal Cell Carcinoma, Cholangiocarcinoma
- Keywords
- BAP1, niraparib, DNA repair, PARP inhibitor, homologous repair deficiency, renal cell carcinoma, cholangiocarcinoma, mesothelioma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Collaborators
- GlaxoSmithKline
- Study start
- 13 Aug 2018 (actual)
- Primary completion
- 30 Aug 2022 (actual)
- Study completion
- 30 Aug 2022 (actual)
- First posted
- 2 Jul 2017 (actual)
- Results
- Posted 15 Sep 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
BAP1 is an ubiquitin ligase that is critical in helping to regulate the cell cycle, cellular differentiation, and cell death. This protein is also intimately involved with DNA double-strand break repair. Germline mutations in the BAP1 gene are associated with a hereditary cancer syndrome that increases the risk of uveal melanoma, mesothelioma and renal cell carcinoma. PARP is another protein that is crucial in DNA repair and enables continued cell replication and survival. It is hypothesized that PARP inhibition with niraparib will result in significant cytoreduction in patient tumors with mutations in BAP1 and other components of the DNA damage response pathway through synthetic lethality. Synthetic lethality is the inhibition of a gene that a cell relies on to compensate for the loss of another gene, resulting in the cell's demise.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Patients in both cohorts will receive niraparib.
| Arm | Type | Receives |
|---|---|---|
| Cohort A | Experimental | Drug: NiraparibThis cohort will enroll patients with mesothelioma, uveal melanoma, renal cell carcinoma (clear cell type), and cholangiocarcinoma. |
| Cohort B | Experimental | Drug: NiraparibThis 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). |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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)
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NiraparibAlso: ZejulaPatients will take 300 mg of niraparib orally once daily each day of a 28 day cycle. | Drug | Cohort A, Cohort B |
Primary outcome
Objective Response Rate (ORR)
Time frame: 1 year
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).
4 secondary outcomes
Progression-Free Survival
Time frame: 8 months
Progression-Free Survival Rate at 3 Months
Time frame: 3 months
Progression-Free Survival Rate at 6 Months
Time frame: 6 months
Overall Survival
Time frame: 10 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39626160George 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thomas George, MD, FACP principal investigator
University of Florida
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Niraparib in people with Mesothelioma and Uveal Melanoma, run by University of Florida at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03207347, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2023; AzTrials last refreshed its copy on 6 Nov 2026.