Niraparib Efficacy in Patient With Unresectable Mesothelioma

NCT05455424 | Completed Phase 2 DMC FDA Drug

• 4 other identifiers: RMH CAN16822022-000198-26ISRCTN16171129MCTA20F\2
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 11

Brief Summary

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.

Conditions

Mesothelioma, Malignant

Keywords

Mesothelioma; Relapsed; Pleural; Peritoneal; Niraparib; PARP-Inhibitors; RECIST; Quality of Life; Phase II; Randomised; Progression-free survival

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  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)

  From date of randomisation until the date of the first documented progression or date of death from any cause, whichever came first, assessed up to 18 months

Secondary Outcomes (6)

• Overall Survival

  From date of randomisation until the date of the first documented progression or date of death from any cause, whichever came first, assessed up to 18 months

• Best overall response (progressive disease, stable disease, partial or complete response)

  From date of randomisation until the date of the first documented progression or date of death from any cause, whichever came first, assessed up to 18 months

• Disease Control

  12 and 24 weeks post randomisation

• Duration of response

  From date of randomisation until the date of the first documented progression or date of death from any cause, whichever came first, assessed up to 18 months

• Treatment compliance

  Up to 24 weeks

Other Outcomes (2)

• Correlate homologous recombination gene alterations and clinical outcome

  From date of randomisation until the date of the first documented progression or date of death from any cause, whichever came first, assessed up to 18 months

• To identify causes of acquired resistance to Niraparib in a subset of patients undergoing optional re-biopsy at disease progression

  From date of randomisation until the date of the first documented progression or date of death from any cause, whichever came first, assessed up to 18 months

Study Arms (2)

Niraparib + ASC

EXPERIMENTAL

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.

Drug: Niraparib Oral Product

Active Symptom Control

ACTIVE COMPARATOR

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.

Other: Active Symptom Control

Interventions

Niraparib Oral Product DRUG

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.

Also known as: Zejula

Niraparib + ASC

Active Symptom Control OTHER

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

Eligibility Criteria

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

You may qualify if:

• Patients must have signed and dated a REC-approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal patient care.
• Patients must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and other requirements of the study
• Histologically confirmed diagnosis of mesothelioma. Any histological subtype (epithelioid, biphasic or sarcomatoid) and any site (e.g. pleural or peritoneal) with an available tissue block. Tissue blocks will be requested at the time of screening.
• Patients must have received prior systemic therapy (any number of lines) for pleural or peritoneal mesothelioma.
• Disease progression must be confirmed per Investigator's assessment prior to screening.
• Any prior treatment must be completed at least 14 days prior to receiving study treatment, where all toxicities have recovered or returned to grade 1, with the exception of alopecia and neuropathy due to chemotherapy which should have returned to grade 2.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1.
• Radiologically assessable disease by modified RECIST (pleural mesothelioma) or RECIST 1.1 (non-pleural mesothelioma or where measurements for modified RECIST cannot be obtained).
• Age ≥ 18 years old.
• Consent to provide mandatory diagnostic tissue blocks and blood samples for translational research, including an optional rebiopsy at progression.
• Adequate organ function, including suitable bone marrow reserve and creatinine clearance.
• Screening laboratory values must meet the following criteria within 48 hours prior to commencement of treatment:
• White blood cells ≥ 2 x 109/L
• Neutrophils ≥ 1.5 x 109/L
• Platelets ≥ 100 x 109/L

You may not qualify if:

• Patients with untreated, symptomatic central nervous system (CNS) metastases, including carcinomatous meningitis, leptomeningeal disease, and radiographic signs of CNS haemorrhage are excluded.
• Patients with untreated third space fluid collection requiring therapeutic drainage are excluded
• Second malignancy within 5 years except cancers definitely treated curative intent (e.g. basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ bladder cancer or in situ cervical cancer).
• Any serious or uncontrolled medical disorder or active infection that, in the opinion of the investigator, may increase the risk associated with study participation, study drug administration, or would impair the ability of the patient to receive protocol therapy.
• Difficulty swallowing or previous significant resection of the stomach or small bowel.
• Patients who have not recovered from the effects of major surgery or significant traumatic injury at least 14 days before the first dose of study treatment.
• Prior exposure to PARP inhibitor or known hypersensitivity to the components of niraparib.
• New York Heart Associated class II or greater heart failure, hepatic \[AST \> 3XULN, ALT \> 3XUL, Total bilirubin \> 1.5XULN\] or renal impairment \[Serum creatinine of \>1.5 X ULN or creatinine clearance (CrCL) ≤ 50 mL/minute (using Cockcroft/Gault formula)\].
• Known alcohol or drug abuse.
• Patients are not permitted to enter any other interventional studies.
• Any patient not able to give consent.
• Any pregnant or breastfeeding patient.
• Patient with known history or current diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukaemia (AML)
• Patient with known history of active tuberculosis.
• Patients with uncontrolled hypertension.

Sponsors & Collaborators

• University Hospital Southampton NHS Foundation Trust: lead
• University of Southampton: collaborator
• British Lung Foundation: collaborator

Study Sites (11)

University Hospital Southampton, Southampton General Hospital

Southampton, Hampshire, SO16 6YD, United Kingdom

Location

Medway NHS Foundation Trust, Medway Maritime Hospital

Gillingham, Kent, ME7 5NY, United Kingdom

Location

Somerset NHS Foundation Trust, Musgrove Park Hospital

Taunton, Somerset, TA1 5DA, United Kingdom

Location

Belfast Health and Social Care Trust, Belfast City Hospital

Belfast, BT9 7AB, United Kingdom

Location

Velindre University NHS Trust, Velindre Cancer Centre

Cardiff, CF15 7QZ, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

Location

The Princess Alexandra Hospital NHS Trust, The Princess Alexandra Hospital

Harlow, CM20 1QX, United Kingdom

Location

Hull University Teaching Hospitals NHS Trust, Castle Hill Hospital

Hull, HU16 5JQ, United Kingdom

Location

Leeds Teaching Hospitals NHS Trust, St James's Hospital

Leeds, LS9 7TF, United Kingdom

Location

University Hospitals of Leicester NHS Trust, Royal Leicester Infirmary

Leicester, LE2 7LX, United Kingdom

Location

Sheffield Teaching Hospitals NHS Foundation Trust, Weston Park Hospital

Sheffield, S10 2JF, United Kingdom

Location

Related Publications (1)

• Fennell D, Griffiths D, Eminton Z, Morgan-Fox A, Hill K, Ewings S, Stuart C, Johnson L, Mallard K, Nye M, Darlison L, Dulloo S, Cave J, Luo JL, Taylor P, Spicer J, Poile C, Bzura A, Griffiths G. Evaluating niraparib versus active symptom control in patients with previously treated mesothelioma (NERO): a study protocol for a multicentre, randomised, two-arm, open-label phase II trial in UK secondary care centres. BMJ Open. 2023 Nov 22;13(11):e073120. doi: 10.1136/bmjopen-2023-073120.

  PMID: 37993149 DERIVED

MeSH Terms

Conditions

Mesothelioma, Malignant; Mesothelioma; Recurrence

Interventions

niraparib

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Dean Fennell

  University of Leicester

  PRINCIPAL INVESTIGATOR

Study Design

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

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

Study Record Dates

• First Submitted: June 8, 2022
• First Posted: July 13, 2022
• Study Start: July 11, 2022
• Primary Completion: January 31, 2025
• Study Completion: January 31, 2025
• Last Updated: May 15, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Anonymous data will be available for request from 3 months after the publication of the results to researchers who provide a completed data sharing request form that describes a methodologically sound proposal, for the purpose of the approved proposal and if appropriate, signed a data-sharing agreement.
• Access Criteria: Data access requests will be reviewed against specific eligibility criteria by the SCTU data custodian and key members of the trial team.

Locations

GB (11)