Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Symptoms and General Pathology

Behaviors and Mental Disorders

Rare Diseases

Mesothelioma

Mesothelioma, Malignant

Disease Progression

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

Quality of Life

Malignant Mesothelioma

Antineoplastic Agents

All Drugs and Chemicals

Channel Blockers

Niraparib

Poly(ADP-ribose) Polymerase Inhibitors

Piperidine

Enzyme Inhibitors

Patients will receive 200/300 mg of niraparib daily for study period of up to 24 weeks. Patients will be treated until disease progression, withdrawal, death or development of significant treatment limiting toxicity. Niraparib will be supplied in oral formulation as 100 mg capsules. The starting dose of Niraparib will be based upon the patient's baseline body weight and/or platelet count:

Participants with a baseline body weight ≥77 kg and baseline platelet count ≥150 x 109/L will be administered niraparib 300 mg daily.

Participants with a baseline body weight \<77 kg or baseline platelet count \<150 x 109/L will be administered niraparib 200 mg daily.

The dose of Niraparib can be reduced in 100 mg increments, to a minimum of 100 mg, per protocol. Dose escalations are not permitted.

Patients in this arm will be managed symptomatically and will be treated as per the standard of care at each participating site. ASC could involve regular specialist follow up; structured assessment of physical, psychological, and social problems; and appropriate treatment, including palliative radiotherapy and steroids.

Niraparib (\[3S\]-3-\[4-\[7-(aminocarbonyl)-2H-indazol-2-yl\] phenyl\] piperidine \[tosylate monohydrate salt\]) is an orally available, potent, and highly selective PARP1 and PARP2 inhibitor. The excipients for niraparib are lactose monohydrate and magnesium stearate. Niraparib will be supplied in bottles containing 72 capsules of 100 mg. The capsules should be swallowed whole with water. The capsules should not be chewed or crushed and can be taken without regard to meals.

Niraparib Oral Product

ASC could involve regular specialist follow up; structured assessment of physical, psychological, and social problems; and appropriate treatment, including palliative radiotherapy and steroids.

Active Symptom Control

Dean Fennell

Multicentre, 2 arm, open-label UK randomised phase II trial to determine the efficacy of niraparib versus active symptom control (ASC) in patients who have relapsed after previously receiving platinum based systemic therapy. 84 patients will be recruited from approximately 10 UK trial network sites.

Mesothelioma is a cancer that is caused by exposure to asbestos, an environmental contaminant. This cancer is incurable and lacks effective treatment, particularly after initial chemotherapy. There has not been a licenced therapy for mesothelioma since 2003, and no treatment has yet demonstrated an improvement in survival following initial chemotherapy. There is an urgent need to explore more effective approaches to therapy. Targeted treatments offer potential hope for the treatment of mesothelioma. A class of drugs called PARP (Poly Adenosine Diphosphate-ribose polymerase) inhibitors have already been proven to improve the survival of patients with breast and ovarian cancers, that carry specific mutations. Mesothelioma has been shown in a recent trial to respond to this class of agent. Further investigation is warranted to test whether PARP inhibitors could be a new treatment option for patients. As with ovarian cancer studies of the past, the NERO trial will test a PARP inhibitor (niraparib) after successful treatment with chemotherapy. Patients whose tumours shrink or stabilise following chemotherapy are expected to have a greater chance of benefit from niraparib. It's not known if niraparib will be able to improve survival of patients with mesothelioma, or indeed whether or not toxicity could occur without benefit. For that reason, patients will be randomised with a 2:1 chance of receiving the drug. Those patients who do not receive niraparib will be closely monitored for signs of early tumour growth so that they can go on to receive an alternative treatment if necessary. If the NERO trial is positive, this study will lead to the approval of a new medicine for use around the world, one that would extend the life expectancy of patients for the first time following initial chemotherapy. NERO will recruit 84 patients over 12 months. Those randomised to receive niraparib will receive a daily dose of 200 mg or 300mg for up to 24 weeks within the trial.

NERO is a multicentre, 2 arm, open-label UK randomised phase II trial comparing Niraparib versus ASC in patients with previously treated mesothelioma.

Niraparib Efficacy in Patient With Unresectable Mesothelioma

Niraparib Efficacy in Patient With Unresectable Mesothelioma: A Randomised Phase II Trial of Niraparib Versus Active Symptom Control in Patients With Previously Treated Mesothelioma

IPD will be made available, including data dictionaries, for approved data sharing requests. Individual participant data will be shared that underlie the results after de-identification and normalisation of information (text, tables, figures, and appendices). The study protocol and statistical analysis plan will also be available. Pseudonymised participant data within the clinical trial dataset will be available for sharing via controlled access by authorised Southampton Clinical Trials Unit (SCTU) staff. The request for data access will need to detail the specific requirements and the proposed research, statistical analysis, publication plan and evidence of research group qualifications. Data will be shared once all parties have signed relevant data sharing documentation covering SCTU conditions for sharing and if required, an additional data sharing agreement from the sponsor. Proposals should be directed to ctu@soton.ac.uk.

Response, progression-free and overall survival will be correlated with somatic alteration of HR genes

Progression-free survival is the determined by modified RECIST (pleural disease), RECIST 1.1 (for non-pleural disease), investigator reported progression or death from any cause (whichever event comes first)

Time from randomisation to death from any cause

The best overall response is the best response recorded from the start of treatment until disease progression or death

Stable disease, partial or complete response

Time from complete or partial response (where this occurs) until progression or death

Assessed by summarising the percentage of the received dose relative to the intended dose at each cycle

Summary statistics and listings will be reported for patients in the safety population and will be summarised by treatment arm with classification by the latest version of MedDRA. Grade will be reported on the CTCAE toxicity scale (version 5.0). Both all cause and treatment related or emergent AEs will be included in the analysis.

University of Southampton

British Lung Foundation

University Hospital Southampton NHS Foundation Trust

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Capecitabine

CECILE VICIER, DR

This study will be to combine oral capecitabine and oral niraparib such thz association may increase clinical benefits of PARP inhibitors in germline BRCA mutated HER2 negative advanced breast cancer patients.

In spite of multimodal treatment, prognosis of HER2 negative metastatic breast cancers remains poor and innovative targeted therapeutic approaches are urgently warranted. While PARP inhibi-tors as single agent have demonstrated moderate improvement in progression-free survival and quality of life in pre-treated HER2 negative advanced breast cancer patients with germline BRCA mutation, they failed to improve overall survival in this setting. In addition, most of clinical trials testing combinations of chemotherapy and PARP inhibitors have been limited by overlapping hematological toxicities, or have used low dosage PARP inhibitors with short exposure time and with uncertain benefits. The therapeutic strategy selected in this study will be to combine oral capecitabine (2 weeks on, 1 week off, as recommended in monotherapy) and oral niraparib (con-tinuously for a cycle of 21 days). Such an association may increase clinical benefits of PARP inhibitors in germline BRCA mutated HER2 negative advanced breast cancer patients, while po-tentially expanding clinical interest of PARP inhibitors in patients without germline BRCA muta-tion (either with or without HRD).

A Phase 1b/2 Trial Evaluating Safety and Efficacy of CAPecitabine in Combination With Ni-rapaRIb in HER2-negative Advanced Breast canCEr

incidence of Dose-Limiting Toxicities (DLT)

rate of patients experiencing an objective response

Plasma concentrations and basic PK parameters of niraparib and capecitabine when adminis-tered in combination

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Niraparib Efficacy in Patient With Unresectable Mesothelioma	NCT05455424	Mesothelioma, M...	Niraparib Oral ... Active Symptom ...	18 Years -	University Hospital Southampton NHS Foundation Trust
A Phase 1b/2 Trial Evaluating Safety and Efficacy of CAPecitabine in Combination With Ni-rapaRIb in HER2-negative Advanced Breast canCEr	NCT05519670	Breast Cancer	Niraparib Oral ...	18 Years -	Institut Paoli-Calmettes
A Phase 1b/2 Trial Evaluating Safety and Efficacy of CAPecitabine in Combination With Ni-rapaRIb in HER2-negative Advanced Breast canCEr	NCT05519670	Breast Cancer	Niraparib Oral ...	18 Years -	Institut Paoli-Calmettes
A Phase 1b/2 Trial Evaluating Safety and Efficacy of CAPecitabine in Combination With Ni-rapaRIb in HER2-negative Advanced Breast canCEr	NCT05519670	Breast Cancer	Niraparib Oral ...	18 Years -	Institut Paoli-Calmettes
Niraparib Efficacy in Patient With Unresectable Mesothelioma	NCT05455424	Mesothelioma, M...	Niraparib Oral ... Active Symptom ...	18 Years -	University Hospital Southampton NHS Foundation Trust
Niraparib Efficacy in Patient With Unresectable Mesothelioma	NCT05455424	Mesothelioma, M...	Niraparib Oral ... Active Symptom ...	18 Years -	University Hospital Southampton NHS Foundation Trust

Spots Global Cancer Trial Database for niraparib oral product