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MesotheliomaPhase 3CONFIRMNCT03063450

CheckpOiNt Blockade For Inhibition of Relapsed Mesothelioma

A Phase 3 study testing Nivolumab in people with Mesothelioma, run by University of Southampton at 24 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

The UK has the highest incidence of mesothelioma. The incidence has risen by 497% since the late 1970's and is increasing worldwide due to continued mining and use of asbestos. For patients with mesothelioma who have relapsed after taking pemetrexed and cisplatin, there is currently no standard treatment, making this… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Mesothelioma
What is being tested?
Nivolumab
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
332 participants
Where
24 sitesUnited Kingdom
Study dates
28 Mar 2017to 7 Feb 2023
Phase
Phase 3
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

  • Signed and dated a REC-approved written informed consent form in accordance with regulatory and institutional guidelines. Must be obtained before the performance of any protocol-related procedures that are not part of normal patient care.
  • Consent to provide tissue and blood samples for research
  • Must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and other requirements of the study
  • Histological confirmation of mesothelioma (any subtype, pleural or peritoneal).
  • Must have received treatment with at least one prior line of treatment. Prior maintenance therapy (e.g. avastin) is allowed and will not count as a line of therapy. Prior lines of antineoplastic therapy, including chemotherapy, surgical resection of lesions, radiation therapy, must be completed within 14 days of receiving nivolumab
  • ECOG PS 0-1
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  • Age ≥18 years
  • Expected survival of at least 12 weeks
  • Radiologically assessable disease by modified RECIST (pleural mesothelioma) or RECIST 1.1 (non-pleural mesothelioma or where measurements for mRECIST cannot be obtained).
  • Evidence of disease progression by CT scan
  • Prior palliative radiotherapy must have been completed at least 14 days prior to study drug administration
  • Screening laboratory values must meet the following criteria within 48 hours prior to commencement of treatment:
  • White blood cells ≥ 2 x 10^9/L ii) Neutrophils ≥1.5 x 10^9/L iii) Platelets ≥ 100 X10^9/L iv) Haemoglobin ≥ 90 g/L v) Serum creatinine of ≤ 1.5 X ULN or creatinine clearance (CrCl) > 50 mL/minute (using Cockcroft/Gault formula) vi) AST ≤ 3 X ULN vii) ALT ≤ 3 X ULN viii) Total bilirubin ≤ 1.5 X ULN (except patients with Gilbert Syndrome, who must have total bilirubin < 51.3 μmol/L) 2 x 10^9/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 HCG) at enrolment and within 24 hours prior to the start of study drug.
  • Women must not be breastfeeding.
  • WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with nivolumab plus 5 half-lives of nivolumab (5 x half-life=125 days) plus 30 days (duration of ovulatory cycle) for a total of 5 months post- treatment completion.
  • Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of investigational product. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile as well as azoospermic men do not require contraception.
  • Expected survival of at least 12 weeks.

Who cannot join

  • Target Disease Exceptions
  • Patients with untreated, symptomatic CNS metastases are excluded. Participants are eligible if CNS metastases are adequately treated and participants are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to treatment assignment. In addition, participants must be either off corticosteroids, or on a stable or decreasing dose of <=10 mg daily prednisone (or equivalent) for at least 2 weeks prior to treatment.
  • Patients with carcinomatous meningitis are excluded.
  • Physical and Laboratory Test Findings
  • 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.
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  • Allergies and Adverse Drug Reactions
  • History of severe hypersensitivity reactions to other monoclonal antibodies
  • Medical History and Concurrent Diseases
  • Patients with active, known or suspected autoimmune disease.
  • Patients with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of the first dose of study drug administration. Inhaled or topical steroids and adrenal replacement steroid doses > 10 mg daily prednisone or equivalent are permitted in the absence of active autoimmune disease.
  • Other active malignancy requiring concurrent intervention.
  • Patients with previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma or breast) are excluded unless a complete remission was achieved at least 2 years prior to study entry AND no additional therapy is required during the study period.
  • 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.
  • All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue not resolved to Grade 1 (NCI CTCAE version 4.03) or baseline before administration of study drug.
  • 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.
  • Known alcohol or drug abuse.
  • Patients who have received prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti- CD137, or anti-CTLA-4 antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) or who have previously taken part in a randomised Bristol Myers Squibb (BMS) clinical trial for nivolumab or ipilimumab including study CA209-743 (CheckMate 172) or in the CCTG trial of pembrolizumab (IND.227).

Trial locations and contacts

24 sites in 1 country.

24 sites in 1 country

United Kingdom24 sites

  • Aberdeen Royal Infirmary

    Aberdeen

  • Basildon University Hospital

    Basildon

  • Belfast City Hospital

    Belfast

  • Royal Bournemouth Hospital

    Bournemouth

  • Addenbrooke's Hospital

    Cambridge

  • East Kent Hospitals University Foundation Trust

    Canterbury, Kent, CT1 3NG

  • Velindre Cancer Centre

    Cardiff

  • Ninewells Hospital

    Dundee

  • Ulster Hospital

    Dundonald, Belfast, BT16 1RH

  • Beatson West of Scotland Cancer Centre

    Glasgow

  • Harrogate District Hospital

    Harrogate

  • Raigmore Hospital

    Inverness, Inverness, IV2 3UJ

  • University Hospitals Morecambe Bay

    Lancaster

  • Leicester Royal Infirmary

    Leicester

  • Barts Cancer Institute

    London

  • University College London Hospitals NHS Foundation Trust

    London

  • Wythenshawe Hospital

    Manchester

  • Northumbria Healthcare NHS Foundation Trust

    Newcastle upon Tyne, Northumberland, NE12 8EW

  • Mount Vernon Cancer Centre

    Northwood

  • Churchill Hopsital

    Oxford

  • Southampton General Hospital

    Southampton

  • Southend Hospital

    Southend-on-Sea

  • Lister Hospital

    Stevenage

  • Musgrove Park Hospital

    Taunton

Other trials in United Kingdom

About this study

Official title: CheckpOiNt Blockade For Inhibition of Relapsed Mesothelioma (CONFIRM): A Phase III Double-Blind, Placebo Controlled Trial to Evaluate the Efficacy of Nivolumab in Relapsed Mesothelioma

The UK has the highest incidence of mesothelioma. The incidence has risen by 497% since the late 1970's and is increasing worldwide due to continued mining and use of asbestos. For patients with mesothelioma who have relapsed after taking pemetrexed and cisplatin, there is currently no standard treatment, making this an urgent unmet need. Recent trials in this area have not found an effective treatment that improves overall survival.

Following a debate in the House of Lords, a national survey assessing the research priorities in mesothelioma found that 'exploiting the potential of immunotherapy' was a top priority. This trial was designed in response to that survey. It uses the immunotherapy agent nivolumab which blocks programmed cell death 1 (PD-1) receptor on activated T-cells (a type of white blood cell forming part of the immune system). Early research has found a dependency of mesothelioma on the PD-1 checkpoint. By attaching to PD-1, nivolumab blocks its action (checkpoint inhibition), preventing it from turning off the T-cell, and therefore allowing the immune system to work. PD-1 checkpoint inhibition has revolutionised the treatment of melanoma and it is hoped to be as effective in mesothelioma.

This trial is a randomised, double blind placebo controlled trial of patients with mesothelioma who are second or third relapse following a platinum based chemotherapy treatment.

Read the detailed description

Effective therapy for relapsed mesothelioma is an unmet need. Despite a significant number of clinical studies in the second line setting, no randomised study to date has been positive. The James Lind Alliance Priority Setting Partnership funded by the NIHR has identified immunotherapy as the number one UK research priority. To date there have been no placebo controlled randomised trials for mesothelioma using PD-L1 or PD-1 checkpoint inhibition. Early promising signals of activity relating to both PD-L1 and PD-1 targeted treatment in mesothelioma implicate a dependency of mesothelioma on this immune checkpoint, and support the development of a randomised phase III trial to evaluate the efficacy of nivolumab. CONFIRM will be the first ever placebo controlled, randomised phase III trial of a PD-1 immune checkpoint inhibitor.

PD-1 checkpoint inhibition has revolutionised the treatment of melanoma and is now standard of care in non-small cell lung cancer, squamous cell cancer head and neck and classical Hodgkin's lymphoma. It is being assessed rigorously in numerous other cancers making its evaluation in mesothelioma timely in CONFIRM.

This trial is a randomised, double blind placebo controlled trial of patients with mesothelioma who are second or third relapse following a platinum based chemotherapy treatment. Patients will be randomised in a 2:1 ratio (nivolumab: placebo).

336 patients will be recruited from 25 UK centres with the last patient having a minimum of 6 months follow up. All patients will be on treatment for 12 months unless they progress or withdrawal prior to this.

Conditions
Mesothelioma
Being tested
Nivolumab, Placebo
Keywords
anti PD-L1, nivolumab, immunotherapy, RECIST, quality of life, survival, immune checkpoint inhibition
Medical subject headings
Mesothelioma

What participants receive

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

  • NivolumabDrug

    Also called Opdivo

    Nivolumab at a dose of 240mg as a 30-minute IV infusion, on Day 1 of every 14 day treatment cycle

  • PlaceboOther

    Placebo consisting of sterile 0.9% sodium chloride as a 30-minute IV infusion, on Day 1 of every 14 day treatment cycle

Study groups in NCT03063450
Study groupRoleWhat they receive
NivolumabExperimentalNivolumab 240mg flat dose Q2W over 30 minutes IV until disease progression, to a maximum of 12 months
Receives: Drug: Nivolumab
PlaceboPlacebo comparatorSterile 0.9% sodium chloride Q2W over 30 minutes IV until disease progression, to a maximum of 12 months
Receives: Other: Placebo

What is being measured

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

  1. Overall survival

    Length of time participants are alive

    Measured: Time from randomisation to date of death from any cause or time of censoring

  2. Progression free survival

    Length of time participants are free of disease progression

    Measured: Time from randomisation to investigator-reported progression, death, or end of study (max. 12 months from last participant randomised)

Secondary outcomes (5)

  1. Overall response rate (modified RECIST or RECIST 1.1)

    Response of disease to treatment

    Measured: From randomisation and while on treatment

  2. EQ-5D-5L

    Quality of life

    Measured: At baseline, after cycles 3 and 6 (each cycle is 14 days) and 1, 6 and 12 months post progression/treatment discontinuation.

  3. CTCAE V4.03

    Adverse events

    Measured: At baseline, after each treatment cycle (each cycle is 14 days) and each follow up visit. Up to 30 days post progression/treatment discontinuation.

  4. Health resource use

    Bespoke health resource use questionnaire capturing information on hospital visits.

    Measured: Up to max. 24 months. At baseline, after cycles 3 and 6 (each cycle is 14 days) and 1, 6 and 12 months post progression/treatment discontinuation.

  5. Progression-free survival (RECIST)

    Time participant is free of disease progression, as measured by RECIST

    Measured: From randomisation until 28 days after completing treatment (max. 12 months), progression, or death

Timeline

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

  1. First posted24 Feb 2017
  2. Study start28 Mar 2017
  3. Primary completion7 Feb 2023
  4. Study completion7 Feb 2023

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
332 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03063450
Sponsor's protocol ID
22864
Other IDs
2016-003111-35, CA209-841, A21400, 2016
Acronym
CONFIRM
Status last verified
May 2024
First submitted
10 Feb 2017
Last updated
10 Apr 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: As a minimum, anonymous data will be available for request from three months after publication of an article, 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 a signed Data Sharing Agreement. Data will be shared once all parties have signed relevant data sharing documentation.

Publications

  • Fennell DA, Kirkpatrick E, Cozens K, Nye M, Lester J, Hanna G, Steele N, Szlosarek P, Danson S, Lord J, Ottensmeier C, Barnes D, Hill S, Kalevras M, Maishman T, Griffiths G. CONFIRM: a double-blind, placebo-controlled phase III clinical trial investigating the effect of nivolumab in patients with relapsed mesothelioma: study protocol for a randomised controlled trial. Trials. 2018 Apr 18;19(1):233. doi: 10.1186/s13063-018-2602-y.

    PubMed 29669604

  • Fennell DA, Ewings S, Ottensmeier C, Califano R, Hanna GG, Hill K, Danson S, Steele N, Nye M, Johnson L, Lord J, Middleton C, Szlosarek P, Chan S, Gaba A, Darlison L, Wells-Jordan P, Richards C, Poile C, Lester JF, Griffiths G; CONFIRM trial investigators. Nivolumab versus placebo in patients with relapsed malignant mesothelioma (CONFIRM): a multicentre, double-blind, randomised, phase 3 trial. Lancet Oncol. 2021 Nov;22(11):1530-1540. doi: 10.1016/S1470-2045(21)00471-X. Epub 2021 Oct 14.

    PubMed 34656227

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Nivolumab in people with Mesothelioma, run by University of Southampton at 24 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 19 inclusion and 18 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 10 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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?

Overall survival (time frame: Time from randomisation to date of death from any cause or time of censoring). The study lists 2 primary outcomes in all. 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 NCT03063450, which also lists 2 linked publications.

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 10 Apr 2025.

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