NCT03531840

Olaparib in People With Malignant Mesothelioma

Completed Phase 2 Results posted Last updated 9 April 2021

What this trial tests

Phase 2 trial testing Olaparib in Mesothelioma in 23 participants. Completed in 21 October 2020.

Timeline

11 July 2018

Primary endpoint
4 December 2019

21 October 2020

Quick facts

Lead sponsor	National Cancer Institute (NCI)
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	23
Start date	11 July 2018
Primary completion	4 December 2019
Estimated completion	21 October 2020
Sites	1 location across United States

Drugs / interventions tested

• Olaparib (olaparib) — full drug profile →
• ClinOmics

Conditions studied

• Mesothelioma — all drugs for Mesothelioma →

Sponsor

National Cancer Institute (NCI)

Who can join

Adults 18 to 99, any sex, with Mesothelioma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With an Objective Response Primary · 6 months after enrollment of last patient

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.

Partial Response

Group	Value	95% CI
Comparison Group 1:Participants With a Germline Mutation in Deoxyribonucleic Acid (DNA) Repair Genes	1
Comparison Group 2: Participants With BRCA1 Associated Protein-1 (BAP1) Somatic Mutations	0
Comparison Group 3: Participants With Neither Germline Mutations Nor BAP 1 Somatic Mutations	0
Participants Not Classified Under Comparison Groups	0

Complete Response

Group	Value	95% CI
Comparison Group 1:Participants With a Germline Mutation in Deoxyribonucleic Acid (DNA) Repair Genes	0
Comparison Group 2: Participants With BRCA1 Associated Protein-1 (BAP1) Somatic Mutations	0
Comparison Group 3: Participants With Neither Germline Mutations Nor BAP 1 Somatic Mutations	0
Participants Not Classified Under Comparison Groups	0

Number of Participants With Germline Deoxyribonucleic Acid (DNA) Repair Mutation Who Experienced Partial or Complete Response. Primary · 6 months after enrollment of last patient

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.

Partial Response

Group	Value	95% CI
Comparison Group 1:Participants With a Germline Mutation in Deoxyribonucleic Acid (DNA) Repair Genes	1

Complete Response

Group	Value	95% CI
Comparison Group 1:Participants With a Germline Mutation in Deoxyribonucleic Acid (DNA) Repair Genes	0

Percentage of Participants With Breast Cancer Type 1 Associated Protein-1 (BAP1) Somatic Mutations Who Experienced Partial or Complete Response. Primary · 6 months after enrollment of last patient

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.

Partial Response

Group	Value	95% CI
Comparison Group 2: Participants With BRCA1 Associated Protein-1 (BAP1) Somatic Mutations	0

Complete Response

Group	Value	95% CI
Comparison Group 2: Participants With BRCA1 Associated Protein-1 (BAP1) Somatic Mutations	0

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. Primary · 6 months after enrollment of last patient

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.

Partial Response

Group	Value	95% CI
Comparison Group 3: Participants With Neither Germline Mutations Nor BAP 1 Somatic Mutations	0

Complete Response

Group	Value	95% CI
Comparison Group 3: Participants With Neither Germline Mutations Nor BAP 1 Somatic Mutations	0

Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) Primary · Adverse events were recorded from the study start date until prior to the study completion date, approximately 27 months and 11 days.

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

Group	Value	95% CI
Comparison Group 1:Participants With a Germline Mutation in Deoxyribonucleic Acid (DNA) Repair Genes	5
Comparison Group 2: Participants With BRCA1 Associated Protein-1 (BAP1) Somatic Mutations	6
Comparison Group 3: Participants With Neither Germline Mutations Nor BAP 1 Somatic Mutations	8
Participants Not Classified Under Comparison Groups	4

Number of Participants With Dose Limiting-toxicities (DLT's) Secondary · 21 days after enrollment of last subject

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

Group	Value	95% CI
Comparison Group 1:Participants With a Germline Mutation in Deoxyribonucleic Acid (DNA) Repair Genes	0
Comparison Group 2: Participants With BRCA1 Associated Protein-1 (BAP1) Somatic Mutations	0
Comparison Group 3: Participants With Neither Germline Mutations Nor BAP 1 Somatic Mutations	0
Participants Not Classified Under Comparison Groups	0

Adverse events — posted to ClinicalTrials.gov

Time frame: Date treatment consent signed to date off study, approximately 18 months and 25 days for Group 1, 27 months and 8 days for Group 2, and 26 months and 18 days for both Group 3 and Participants not classified under comparison groups... Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

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

Serious: 1/5 (20%)

Deaths: 5/5

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

Serious: 4/6 (67%)

Deaths: 5/6

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

Serious: 1/8 (13%)

Deaths: 5/8

Participants Not Classified Under Comparison Groups

Serious: 1/4 (25%)

Deaths: 3/4

Serious adverse events (9 terms)

Reaction	System	Comparison Group 1:Partici…	Comparison Group 2: Partic…	Comparison Group 3: Partic…	Participants Not Classifie…
Abdominal pain	Gastrointestinal disorders	—	—	—	—
Aspiration	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Disease progression	General disorders	—	—	—	—
Dyspnea	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Eye disorders - Other, Eye disorders - Lt orbital solitary	Eye disorders	—	—	—	—
Hypercalcemia	Metabolism and nutrition disorders	—	—	—	—
Lung infection	Infections and infestations	—	—	—	—
Non-cardiac chest pain	Musculoskeletal and connective tissue disorders	—	—	—	—
Pain	General disorders	—	—	—	—

Other adverse events (106 terms — click to expand)

Reaction	System	Comparison Group 1:Partici…	Comparison Group 2: Partic…	Comparison Group 3: Partic…	Participants Not Classifie…
Lymphocyte count decreased	Investigations	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—
Anemia	Blood and lymphatic system disorders	—	—	—	—
Fatigue	General disorders	—	—	—	—
Hypoalbuminemia	Metabolism and nutrition disorders	—	—	—	—
Anorexia	Metabolism and nutrition disorders	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—
Creatinine increased	Investigations	—	—	—	—
Diarrhea	Gastrointestinal disorders	—	—	—	—
Hypercalcemia	Metabolism and nutrition disorders	—	—	—	—
Hyperglycemia	Metabolism and nutrition disorders	—	—	—	—
Sinus tachycardia	Cardiac disorders	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—
Activated partial thromboplastin time prolonged	Investigations	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—
Dysgeusia	Nervous system disorders	—	—	—	—
Dyspepsia	Gastrointestinal disorders	—	—	—	—
Dyspnea	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Flu like symptoms	General disorders	—	—	—	—
Hypertension	Vascular disorders	—	—	—	—
Hypoglycemia	Metabolism and nutrition disorders	—	—	—	—
Hypokalemia	Metabolism and nutrition disorders	—	—	—	—
Hyponatremia	Metabolism and nutrition disorders	—	—	—	—
Insomnia	Psychiatric disorders	—	—	—	—
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Productive cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Renal and urinary disorders - Other, creatinine clearance decreased	Renal and urinary disorders	—	—	—	—
Weight loss	Investigations	—	—	—	—
White blood cell decreased	Investigations	—	—	—	—
Abdominal distension	Gastrointestinal disorders	—	—	—	—
Alkaline phosphatase increased	Investigations	—	—	—	—
Allergic rhinitis	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Anxiety	Psychiatric disorders	—	—	—	—
Ascites	Gastrointestinal disorders	—	—	—	—
Belching	Gastrointestinal disorders	—	—	—	—

Most-reported serious reactions: Abdominal pain, Aspiration, Disease progression, Dyspnea, Eye disorders - Other, Eye disorders - Lt orbital solitary, Hypercalcemia, Lung infection, Non-cardiac chest pain.

Data from ClinicalTrials.gov NCT03531840 adverse events section.

Sponsor's own description

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.

...

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Mesothelioma: Scientific clues for prevention, diagnosis, and therapy.
   Carbone M, Adusumilli PS, Alexander HR, Baas P, et al · · 2019 · cited 353× · PMID 31283845 · DOI 10.3322/caac.21572
2. Biological Mechanisms and Clinical Significance of <i>BAP1</i> Mutations in Human Cancer.
   Carbone M, Harbour JW, Brugarolas J, Bononi A, et al · · 2020 · cited 224× · PMID 32690542 · DOI 10.1158/2159-8290.cd-19-1220
3. BAP1: Not just a BRCA1-associated protein.
   Louie BH, Kurzrock R. · · 2020 · cited 135× · PMID 32877777 · DOI 10.1016/j.ctrv.2020.102091
4. Inherited predisposition to malignant mesothelioma and overall survival following platinum chemotherapy.
   Hassan R, Morrow B, Thomas A, Walsh T, et al · · 2019 · cited 112× · PMID 30975761 · DOI 10.1073/pnas.1821510116
5. Emerging Treatments for Malignant Pleural Mesothelioma: Where Are We Heading?
   Cantini L, Hassan R, Sterman DH, Sterman DH, et al · · 2020 · cited 47× · PMID 32226777 · DOI 10.3389/fonc.2020.00343
6. Phase 2 Study of Olaparib in Malignant Mesothelioma and Correlation of Efficacy With Germline or Somatic Mutations in <i>BAP1</i> Gene.
   Ghafoor A, Mian I, Wagner C, Mallory Y, et al · · 2021 · cited 41× · PMID 34661178 · DOI 10.1016/j.jtocrr.2021.100231
7. Tumor Immune Microenvironment and Genetic Alterations in Mesothelioma.
   Hiltbrunner S, Mannarino L, Kirschner MB, Opitz I, et al · · 2021 · cited 41× · PMID 34249695 · DOI 10.3389/fonc.2021.660039
8. Comprehensive genomic and tumour immune profiling reveals potential therapeutic targets in malignant pleural mesothelioma.
   Creaney J, Patch AM, Addala V, Sneddon SA, et al · · 2022 · cited 39× · PMID 35637530 · DOI 10.1186/s13073-022-01060-8