Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Mesothelioma

Mesothelioma, Malignant

Adenoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Mesothelial

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Pleural Neoplasms

Lung Diseases

Respiratory Tract Diseases

Malignant Mesothelioma

Antineoplastic Agents

All Drugs and Chemicals

Olaparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

All subjects will take olaparib by mouth twice per day until disease progression or unacceptable toxicity

ClinOmics

Raffit Hassan, M.D.

Background:

The drug olaparib may stop cancer cells from fixing damage to their deoxyribonucleic acid (DNA). It has been approved to treat certain cancers in people that were born with a mutation in the breast cancer (BRCA) gene. It has not been approved for treating mesothelioma. But some people with mesothelioma have mutations in a gene, BRCA1 Associated Protein 1 (BAP1) related to BRCA. Researchers want to see if olaparib can work in patients with mutations in this gene. They also want to see if works on mutations in other genes or patients without any mutations. They want to see if olaparib causes mesothelioma tumors to shrink.

Objective:

To study the effect of olaparib on mesothelioma.

Eligibility:

People ages 18 and older with malignant mesothelioma that has already been treated

Design:

Participants will be screened with

Sample of tumor tissue or fluid

Medical history

Physical exam

Blood, heart, and urine tests

Scans and x-rays

Participants will give blood and tissue samples. These will be genetically tested.

The study will be done in 21-day cycles.

Participants will take tables of the study drug 2 times each day. They will get information on what food and drugs to avoid during the study. They will get information about birth control. They will keep a diary of doses and symptoms.

Participants will have blood and urine tests and scans every few weeks.

Participants will be told any important genetic testing results.

Participants will stay in the study until their disease gets worse or the participant or their doctor chooses to stop it.

About 30 days after stopping the study drug, participants will have a follow-up visit. They will have a medical history, physical exam, blood tests, and scans.

Some participants will continue to have scans every 6 weeks.

...

Background:

* Malignant mesothelioma is an invasive and often fatal neoplasm that arises from mesothelium that lines several organs.
* Recent studies have identified germline mutations in the gene encoding breast cancer type 1 (BRCA1) associated protein-1 (BAP1) which can predispose to mesothelioma
* In addition to mesothelioma, germline BAP1 mutations confer increased susceptibility for the development of several other tumors including uveal melanoma, cutaneous melanoma, renal cell cancers and possibly other cancers
* In addition to BAP1, we found several novel germline variants that have previously not been associated with risk of developing mesothelioma.
* As evidenced by recent data derived from ovarian and prostate cancer patients, mutations in deoxyribonucleic acid (DNA) repair genes can define subgroups of cancer patients with distinct vulnerabilities to DNA damage response inhibitors.
* Olaparib is a Poly (ADP-ribose) polymerase (PARP) inhibitor indicated as monotherapy in patients with deleterious or suspected deleterious germline BRCA mutated
* Both established and patient derived mesothelioma cell lines with mutated DNA repair genes are sensitive to olaparib.

Objective:

-Determine the efficacy with respect to objective response rate of olaparib in patients with malignant mesothelioma based on somatic or germline mutation status of DNA repair genes

Eligibility:

* Patients must have progressive, histologically or cytologically confirmed malignant mesothelioma.
* Age greater than or equal to 18 years
* Patients must have received prior platinum and pemetrexed based therapies
* Adequate organ and bone marrow function

Design:

* This is a phase II, single center study of olaparib in subjects with malignant mesothelioma
* All subjects will take olaparib by mouth twice daily until disease progression or intolerable side effects
* Subjects will be assessed for safety (continuously) and efficacy (every 6 weeks)
* Subjects will be analyzed in 3 separate comparison groups according to their mutation status

  * Comparison Group 1: Patients with a germline mutation in DNA repair genes
  * Comparison Group 2: Patients with BAP1 somatic mutations
  * Comparison Group 3: Patients with neither germline mutations nor BAP 1 somatic mutations
* Up to 30 evaluable subjects will be enrolled

Olaparib in People With Malignant Mesothelioma

Phase II Study of Olaparib in Subjects With Malignant Mesothelioma

Number of participants overall who experienced partial or complete response. Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, and the Malignant Pleural Mesothelioma (MPM) criteria. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Complete Response is disappearance of all target lesions.

Number of participants with germline deoxyribonucleic acid (DNA) repair mutation who experienced partial or complete response. Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, and the Malignant Pleural Mesothelioma (MPM) criteria. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Complete Response is disappearance of all target lesions.

Percentage of participants with germline deoxyribonucleic acid (DNA) repair mutation who experienced partial or complete response. Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, and the Malignant Pleural Mesothelioma (MPM) criteria. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Complete Response is disappearance of all target lesions.

Percentage of subjects with neither germline DNA repair mutations nor somatic BAP1 mutations who experienced partial or complete response.Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, and the Malignant Pleural Mesothelioma (MPM) criteria. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Complete Response is disappearance of all target lesions.

Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Dose Limiting-toxicities (DLT's) is defined as

National Cancer Institute (NCI)

Principal Investigator

Data is grouped as specified per protocol.

Participants With a Germline Mutation in Deoxyribonucleic Acid (DNA) Repair Genes

Comparison Group 1:Participants With a Germline Mutation in Deoxyribonucleic Acid (DNA) Repair Genes

Participants With BRCA1 Associated Protein-1 (BAP1) Somatic Mutations

Comparison Group 2: Participants With BRCA1 Associated Protein-1 (BAP1) Somatic Mutations

Participants With no tumor tissue available for somatic mutation

Comparison Group 3: Participants With Neither Germline Mutations Nor BAP 1 Somatic Mutations

Participants Not Classified Under Comparison Groups

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Canada

Region of Enrollment

Dr. Raffit Hassan

Partial Response

Complete Response

Participants With Neither Germline Mutations Nor BAP 1 Somatic Mutations

Participants with no tumor tissue available for somatic mutation

Number of Participants With an Objective Response

Per protocol, this outcome measure was only assessed in participants in Comparison Group 1.

Number of Participants With Germline Deoxyribonucleic Acid (DNA) Repair Mutation Who Experienced Partial or Complete Response.

Per protocol, this outcome measure was only assessed in participants in Comparison Group 2.

Percentage of Participants With Breast Cancer Type 1 Associated Protein-1 (BAP1) Somatic Mutations Who Experienced Partial or Complete Response.

Per protocol, this outcome measure was only assessed in participants in Comparison Group 3.

Percentage of Subjects With Neither Germline Deoxyribonuclecic Acid (DNA) Repair Mutations Nor Somatic Breast Cancer Type 1 Associated Protein-1 (BAP1) Mutations Who Experienced Partial or Complete Response.

Comparison Group 2 Participants With BRCA1 Associated Protein-1 (BAP1) Somatic Mutations

Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

Number of Participants With Dose Limiting-toxicities (DLT's)

Overall Study

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma

Cholangiocarcinoma

Melanoma

Carcinoma, Renal Cell

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Adenocarcinoma

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Bile Duct Cancer

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Intraocular Melanoma

Neuroendocrine Tumor

Neuroepithelioma

Niraparib

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

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).

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

Thomas George, MD, FACP

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.

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.

Patients in both cohorts will receive niraparib.

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

A Phase II Trial of the PARP Inhibitor, Niraparib, in BAP1 and Other DNA Damage Response (DDR) Pathway Deficient Neoplasms (UF-STO-ETI-001)

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).

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.

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.

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.

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.

GlaxoSmithKline

University of Florida

All adverse events were assessed by the principal investigator, the treating sub-investigator, and/or the study coordinator. Adverse events were assessed by physical examination, labs, and subject self-reports.

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

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

Cohort A

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).

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

Cohort B

Cohort B (Closed to Enrollment)

Allison Allegra

The analysis population for both cohorts only includes those subjects with at least one RECIST response assessment at the end of treatment. 6 subjects (5 subjects in Cohort A and 1 subject in Cohort B) did not have at lease one RECIST response assessment at the end of treatment and are not included in the analysis population.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Olaparib in People With Malignant Mesothelioma	NCT03531840	Mesothelioma	Olaparib ClinOmics	18 Years - 99 Years	National Institutes of Health Clinical Center (CC)
Olaparib in People With Malignant Mesothelioma	NCT03531840	Mesothelioma	Olaparib ClinOmics	18 Years - 99 Years	National Institutes of Health Clinical Center (CC)
A Trial of Niraparib in BAP1 and Other DNA Damage Response (DDR) Deficient Neoplasms (UF-STO-ETI-001)	NCT03207347	Mesothelioma Uveal Melanoma Renal Cell Carc... Cholangiocarcin...	Niraparib	18 Years - 80 Years	University of Florida
Olaparib in People With Malignant Mesothelioma	NCT03531840	Mesothelioma	Olaparib ClinOmics	18 Years - 99 Years	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for bap1

Every month we try and update this database with for bap1 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for bap1

Every month we try and update this database with for bap1 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for bap1 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.