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Mesothelioma, MalignantPhase 2NERONCT05455424

Niraparib Efficacy in Patient With Unresectable Mesothelioma

A Phase 2 study testing Niraparib Oral Product in people with Mesothelioma, Malignant, run by University Hospital Southampton NHS Foundation Trust at 11 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Mesothelioma, Malignant
What is being tested?
Niraparib Oral Product
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
88 participants
Where
11 sitesUnited Kingdom
Study dates
11 Jul 2022to 31 Jan 2025
Phase
Phase 2
Are there results?
None posted in the registry

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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
  • Haemoglobin ≥ 90 g/L
  • Serum creatinine of ≤ 1.5 X ULN or creatinine clearance (CrCl) > 50 mL/minute (using Cockcroft/Gault formula)
  • AST ≤ 3 x ULN OR ALT ≤ 3 x ULN (if both are assessed, both need to be ≤ 3 x ULN)
  • Total bilirubin ≤ 1.5 x ULN (except patients with Gilbert Syndrome, who must have total bilirubin < 51.3 μmol/L)
  • Reproductive status:
  • Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of Human Chorionic Gonadotropin) at enrolment and within 24 hours prior to the start of study treatment. An extension up to 3 days prior to the start of study treatment may be permissible in situations where results cannot be obtained within a 24-hour window.
  • Women must not be breastfeeding
  • WOCBP must agree to use a highly effective method of contraception for the duration of treatment and 180 days after the last dose ASC+Niraparib.
  • Men who are sexually active with WOCBP must use the contraceptive methods outlines in the protocol for the duration of treatment and for 90 days after the last dose of ASC+Niraparib
  • Expected survival of at least 12 weeks per Investigator's assessment

Who cannot join

  • 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.
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  • 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.
  • Participants have current active pneumonitis within 90 days of planned start of the study or a known history of interstitial lung disease, drug-related pneumonitis, or radiation pneumonitis requiring steroid treatment.
  • Patients that have received colony-stimulating factors (eg, granulocyte macrophage colony-stimulating factor or recombinant erythropoietin) within 2 weeks prior to the first dose of study treatment.
  • Live vaccines within 30 days prior to the first dose of study treatment and while participating in this clinical study.
  • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
  • Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection.

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

United Kingdom11 sites

  • Belfast Health and Social Care Trust, Belfast City Hospital

    Belfast, BT9 7AB

  • Velindre University NHS Trust, Velindre Cancer Centre

    Cardiff, CF15 7QZ

  • Medway NHS Foundation Trust, Medway Maritime Hospital

    Gillingham, Kent, ME7 5NY

  • Beatson West of Scotland Cancer Centre

    Glasgow, G12 0YN

  • The Princess Alexandra Hospital NHS Trust, The Princess Alexandra Hospital

    Harlow, CM20 1QX

  • Hull University Teaching Hospitals NHS Trust, Castle Hill Hospital

    Hull, HU16 5JQ

  • Leeds Teaching Hospitals NHS Trust, St James's Hospital

    Leeds, LS9 7TF

  • University Hospitals of Leicester NHS Trust, Royal Leicester Infirmary

    Leicester, LE2 7LX

  • Sheffield Teaching Hospitals NHS Foundation Trust, Weston Park Hospital

    Sheffield, S10 2JF

  • University Hospital Southampton, Southampton General Hospital

    Southampton, Hampshire, SO16 6YD

  • Somerset NHS Foundation Trust, Musgrove Park Hospital

    Taunton, Somerset, TA1 5DA

Other trials in United Kingdom

About this study

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

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.

Read the detailed description

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.

Being tested
Niraparib Oral Product, Active Symptom Control
Keywords
Mesothelioma, Relapsed, Pleural, Peritoneal, Niraparib, PARP-Inhibitors, RECIST, Quality of Life, Phase II, Randomised, Progression-free survival
Medical subject headings
Mesothelioma, Malignant, Mesothelioma, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Niraparib Oral ProductDrug

    Also called Zejula

    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.

  • Active Symptom ControlOther

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

Study groups in NCT05455424
Study groupRoleWhat they receive
Niraparib + ASCExperimentalPatients 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.
Receives: Drug: Niraparib Oral Product
Active Symptom ControlActive comparatorPatients 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.
Receives: Other: Active Symptom Control

What is being measured

The primary outcome is the main question the study is designed to answer.

  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)

    Measured: 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)

  1. Overall Survival

    Time from randomisation to death from any cause

    Measured: 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

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

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

    Measured: 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

  3. Disease Control

    Stable disease, partial or complete response

    Measured: 12 and 24 weeks post randomisation

  4. Duration of response

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

    Measured: 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

  5. Treatment compliance

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

    Measured: Up to 24 weeks

  6. Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

    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.

    Measured: At the end of each treatment cycle (each cycle is 21 days, with a maximum of 8 cycles of treatment) for 100 days post treatment discontinuation and for ongoing drug-related AE's until resolved, return to baseline, or deemed irreversible

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jul 2022
  2. Study start11 Jul 2022
  3. Primary completion31 Jan 2025
  4. Study completion31 Jan 2025

Resources

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
Randomised
Intervention model
Parallel groups
Model description
NERO is a multicentre, 2 arm, open-label UK randomised phase II trial comparing Niraparib versus ASC in patients with previously treated mesothelioma.
Masking
None (open label)
Enrolment
88 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05455424
Sponsor's protocol ID
RMH CAN1682
Other IDs
2022-000198-26, ISRCTN16171129, MCTA20F\2
Acronym
NERO
Status last verified
May 2025
First submitted
8 Jun 2022
Last updated
15 May 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • 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.

    PubMed 37993149

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Niraparib Oral Product in people with Mesothelioma, Malignant, run by University Hospital Southampton NHS Foundation Trust at 11 sites in United Kingdom.

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 25 inclusion and 20 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 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United Kingdom. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Progression-free survival (time frame: 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). 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 NCT05455424, 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 May 2025.

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