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AzTrials

MesotheliomaPhase 2/3NCT02784171

Pembrolizumab in Patients With Advanced Malignant Pleural Mesothelioma

A Phase 2/3 study testing Cisplatin, Pemetrexed and Pembrolizumab in people with Mesothelioma, run by Canadian Cancer Trials Group at 57 sites in 3 countries.

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

Pembrolizumab is a new type of drug for mesothelioma (immunotherapy). Laboratory tests show that this drug works by helping improve the body's immune response to help fight cancer. Pembrolizumab may help the immune system to recognize cancer cells and slow down the growth and/or spreading of cancer. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Mesothelioma
What is being tested?
Cisplatin, Pemetrexed and Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
520 participants
Where
57 sitesin 3 countries
Study dates
11 Nov 2016to 11 Oct 2024
Phase
Phase 2/3
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 histologically confirmed malignant pleural mesothelioma. Patients must be eligible to receive standard chemotherapy with pemetrexed and cisplatin and have no contraindications to standard chemotherapy.
  • Patients must have unresectable advanced and/or metastatic disease, incurable by standard therapies.
  • All patients must have a cellular tumour block from their primary or metastatic tumour available and consent to release the block/recently cut slides for correlative analyses (See Section 11.0) and the centre/pathologist must have agreed to the submission of the specimen(s).
  • Presence of radiologically documented disease. At least one site of disease must be unidimensionally measurable as follows:
  • CT scan (with slice thickness of ≤ 5 mm): ≥ 10 mm --> longest diameter
  • Physical exam (using calipers): ≥ 10 mm
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  • Lymph nodes by CT scan ≥ 15 mm --> measured in short axis
  • All radiology studies must be performed within 21 days prior to registration (exception: within 28 days if negative).
  • Age ≥ 18 years.
  • ECOG performance status 0 or 1.
  • Previous Therapy
  • Cytotoxic Chemotherapy:
  • Patients must not have received prior chemotherapy for any stage of advanced/metastatic disease.
  • Patients who received previous (neo)adjuvant cisplatin-based systemic chemotherapy must have received the last dose of chemotherapy at least 12 months before registration. Please contact CCTG PRIOR to randomization for such patients.
  • Other Anti-Cancer Therapy:
  • Patients may not have received targeted small molecule therapy, immunotherapies and viral therapies, biologic therapies and angiogenesis inhibitors for advanced/metastatic disease, or any prior immunotherapy for any stage of disease.
  • Radiation:
  • Patients may have had prior radiation therapy, but NOT to the thorax unless clear disease progression has been demonstrated and confirmed with CCTG. A minimum of 28 days must have elapsed between the end of radiotherapy and registration onto the study. Radiation must have involved < 30% of functioning bone marrow and there must be measurable disease outside the previously irradiated area (patients whose sole site of disease (for example pleural rind) is in a previously irradiated area are ineligible UNLESS there is evidence of progression, or new lesions have been documented, in the irradiated field). Please contact CCTG PRIOR to randomization if the patient has received prior thoracic radiation. Patients must have recovered from any acute toxic effects from radiation prior to registration.
  • Previous Surgery:
  • Previous major surgery is permitted provided that it has been at least 28 days prior to patient registration and that wound healing has occurred.
  • Lab Requirements:
  • Absolute neutrophils ≥ 1.5 x 10^9/L
  • Platelets ≥ 100 x 10^9/L
  • Hemoglobin ≥ 90 g/L
  • Bilirubin ≤ 1.5 x ULN (upper limit of normal)
  • AST and ALT ≤ 2.5 x ULN
  • Serum creatinine < 1.25 x ULN or Creatinine clearance ≥ 50 mL/min
  • Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements.
  • Patients must be accessible for treatment, response assessment and follow-up. Patients registered on this trial must be treated and followed at the participating centre.
  • In accordance with CCTG policy, protocol treatment is to begin within 2 working days of patient randomization.
  • Women/men of childbearing potential must have agreed to use two highly effective contraceptive methods during the study and for six months after discontinuation.
  • Patient must be able (i.e. sufficiently fluent) and willing to complete the quality of life questionnaires.

Who cannot join

  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (at doses more than 10 mg prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first and any dose of trial treatment.
  • Has active autoimmune disease that has required systemic treatment in the past 3 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs) or history of allogeneic transplantation. Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Must not have received a live vaccine within 30 days of planned start of study therapy.
  • Patients with known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
  • Patients who have experienced untreated and/or uncontrolled cardiovascular conditions and/or have symptomatic cardiac dysfunction including cardiac ventricular arrhythmias requiring medication, history of 2nd or 3rd degree atrioventricular conduction defects) or who have had unstable angina congestive heart failure or myocardial infarction within the previous year. Patients with a significant cardiac history, this includes hypertension, even if controlled, should have a LVEF ≥ 50%.
  • Patients with a history of other malignancies unless having undergone curative therapy (i.e. resection, radiation, etc) and do not require concurrent anticancer therapy.
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  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to pembrolizumab or any of the other chemotherapy agents.
  • Concurrent treatment with other investigational drugs or anti0cancer therapy.
  • Patients with serious illness or medical condition that would not permit the patient to be managed according to the protocol including, but not limited to:
  • History of significant neurologic or psychiatric disorder which would impair the ability to obtain consent or limit compliance with study requirements.
  • Active infection requiring systemic therapy; (including any patient known to have active hepatitis B, hepatitis C or human immunodeficiency virus (HIV) [note: testing in asymptomatic patients is not required] or tuberculosis).
  • Known history of, or any evidence of active, non-infectious pneumonitis.
  • Any other medical conditions that might be aggravated by treatment.
  • Serious or non-healing wound, ulcer, or bone fracture.
  • Patients with evidence of interstitial lung disease.
  • Patients with severe/uncontrollable tumor pain that requires radiation prior to starting on systemic therapy.
  • Pregnant or lactating women. (N.B.: All women of childbearing potential must have a negative pregnancy test within 72 hours prior to registration).

Trial locations and contacts

57 sites in 3 countries.

57 sites in 3 countries

France25 sites

  • CHU - Angers

    Angers, 49033

  • Hopital Jean Minjoz

    Besançon, 25030

  • Institut Bergonie

    Bordeaux, 33076

  • Boulogne - Ambroise Pare

    Boulogne, 92104

  • Caen - CHU

    Caen, 14000

  • Clermont-Ferrand - CHU

    Clermont-Ferrand, 63003

  • Centre Hospitalier Intercommunal de Creteil

    Créteil, 94000

  • Centre Hospitalier du Mans

    Le Mans, 72037

  • Lille - Hopital Calmette

    Lille, 59037

  • CHU Dupuytren

    Limoges, FR, 87042

  • Hopital du Scorff

    Lorient, FR, 56100

  • Marseille - Hopital Nord

    Marseille, 13915

  • Study site

    Montpellier, CEDEX 5

  • Centre Hospitalier de Mulhouse

    Mulhouse, 68070

  • Centre Rene Gauducheau

    Nantes, 44805

  • AP-HP Hopital Tenon

    Paris, Cedex 20, 75970

  • Hopital Bichat

    Paris, 75877

  • Lyon URCOT

    Pierre-Bénite, FR, 69310

  • CHU Rennes - Hopital Pontchaillou

    Rennes, FR, 35033

  • Nouvel Hopital Civil Hopitaux

    Strasbourg, 67091

  • CHITS Toulon Sainte Musse

    Toulon, 83056

  • Hopital Larrey

    Toulouse, 31059

  • CHRU de Tours - Hopital Bretonneau

    Tours, Tours Cedex 9, 37044

  • Centre Alexis Vautrin

    Vandœuvre-lès-Nancy, Cedex, 54500

  • Institut Gustave-Roussy

    Villejuif, FR, 94805

Other trials in France

Italy19 sites

  • Oncologia SS Antonio e Biagio Alessandria

    Alessandria, AL, 15121

  • Azienda Ospedaliera San Giuseppe Moscati

    Avellino, AV, 83100

  • IRCCS Ospedale Oncologico Giovanni Paolo II

    Bari, BA, 70124

  • Oncologia Medica Humanitas Gavazzeni Bergamo

    Bergamo, BG, 24125

  • PO A Perrino ASL Brindisi - UOC Oncologia Medica

    Brindisi, 72100

  • Azienda Ospedaliera Garibaldi Nesima

    Catania, CT, 95123

  • AOU Policlinico Vittorio Emanuele UOC di Oncologia

    Catania, 95125

  • U.O. di Oncologia Ospedale Villa Scassi

    Genova, 16149

  • Intstituto Scientifico Romangnolo

    Meldola, 47014

  • Fondazione IRCCS Istituto Nazionale dei Tumori

    Milan, 20133

  • U.O.C. di Oncologia U.L.S.S. 13

    Mirano, 30035

  • Azienda Ospedaliera di Rilievo Nazionale

    Naples, 80131

  • Dott. Fortunato Ciardiello,Cattedra Oncologia Medica

    Naples, 80131

  • U.O.S.D. Day Hospital Oncologico-Pneumologico

    Naples, 80131

  • Unita Sperimentazioni Cliniche Istituto per lo

    Naples, 80131

  • Azienda USL di Piacenza, Ospedale Gugliemimo Salieto

    Piacenza, 29100

  • Oncologia Medica IRCCS Arcispedale Maria

    Reggio Emilia, RE, 42123

  • Istituti Fisioterapici Ospitalieri IFO Istituto

    Rome, RM, 00144

  • Instituto Clinico Humanitas

    Rozzano (MI), Lombardy, 20089

Other trials in Italy

Canada13 sites

  • Tom Baker Cancer Centre

    Calgary, Alberta, T2N 4N2

  • Cross Cancer Institute

    Edmonton, Alberta, T6G 1Z2

  • Juravinski Cancer Centre at Hamilton Health Sciences

    Hamilton, Ontario, L8V 5C2

  • BCCA - Cancer Centre for the Southern Interior

    Kelowna, British Columbia, V1Y 5L3

  • London Regional Cancer Program

    London, Ontario, N6A 5W9

  • CHUM-Centre Hospitalier de l'Universite de Montreal

    Montreal, Quebec, H2X 3E4

  • The Research Institute of the McGill University

    Montreal, Quebec, H4A 3J1

  • Ottawa Hospital Research Institute

    Ottawa, Ontario, K1H 8L6

  • University Institute of Cardiology and

    Québec, Quebec, G1V 4G5

  • Allan Blair Cancer Centre

    Regina, Saskatchewan, S4T 7T1

  • BCCA - Fraser Valley Cancer Centre

    Surrey, British Columbia, V3V 1Z2

  • University Health Network

    Toronto, Ontario, M5G 2M9

  • CancerCare Manitoba

    Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

About this study

Official title: A Phase II/III Randomized Study of Pembrolizumab in Patients With Advanced Malignant Pleural Mesothelioma

Pembrolizumab is a new type of drug for mesothelioma (immunotherapy). Laboratory tests show that this drug works by helping improve the body's immune response to help fight cancer. Pembrolizumab may help the immune system to recognize cancer cells and slow down the growth and/or spreading of cancer.

Read the detailed description

The purpose of this study is to find out what effects a new drug, pembrolizumab has on this type of cancer and if it can offer better results than standard pemetrexed and platinum-based chemotherapy alone. This study will also look at side effects and how the treatments impact quality of life

Conditions
Mesothelioma
Medical subject headings
Mesothelioma

What participants receive

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

Study groups in NCT02784171
Study groupRoleWhat they receive
Arm A - Cisplatin/PemetrexedActive comparatorPemetrexed 500 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin 75 mg/m2 IV Day 1 every 21 days for 6 cycles
Receives: Drug: Cisplatin; Drug: Pemetrexed
Arm B - Cisplatin/Pemetrexed/PembrolizumabActive comparatorPembrolizumab 200 mg* IV Day 1 over 30 min every 21 days for a total of 2 years Pemetrexed 500 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin 75 mg/m2 IV Day 1 every 21 days for 6 cycles
Receives: Drug: Cisplatin; Drug: Pemetrexed; Drug: Pembrolizumab
Arm C - Pembrolizumab (Phase II only)Active comparatorPembrolizumab 200 mg* IV 30 min Day 1 every 21 days for a total of 2 years
Receives: Drug: Pembrolizumab

What is being measured

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

  1. Phase II: Progression Free Survival Measured as Time From Randomization to First Observation of Objective Disease Relapse or Progression

    PFS was calculated for all randomized patients from the day of randomization until the first observation of disease progression (date of objective relapse or progression of Relapse/Progression Report) or death due to any cause (recorded in Date/Cause of Death Section of Death Report).

    Measured: PFS was monitored continuously, with assessments every 6 weeks for 3 visits, then every 12 weeks, 4 weeks post-discontinuation, every 12 weeks until progression, and every 24 weeks until death, over an average of 16.2 months.

  2. Phase III: Overall Survival Defined as Time From Randomization to the Date of Death From Any Cause

    Overall survival was defined as time from the day of randomization to death for patients died. For patients still alive at time of data-cutoff for analysis, it was censored at the last day the patients were known alive as the last of all dates .

    Measured: Survival was monitored continuously throughout the study and during follow-up. Patients were evaluated for each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.

Secondary outcomes (2)

  1. Phase III: Progression Free Survival Measured as Time From Randomization to First Observation of Objective Disease Relapse or Progression

    PFS was calculated for all randomized patients from the day of randomization until the first observation of disease progression (date of objective relapse or progression of Relapse/Progression Report) or death due to any cause (recorded in Date/Cause of Death Section of Death Report). The primary analysis for PFS was based on the progression evaluated in this study using mesothelioma-modified RECIST (mRECIST) conducted by blinded independent review (BICR).

    Measured: PFS was monitored continuously, with assessments every 6 weeks for 3 visits, then every 12 weeks, 4 weeks post-discontinuation, every 12 weeks until progression, and every 24 weeks until death, over an average of 16.2 months.

  2. Phase III: Objective Response Rate

    Objective response rate was defined as the proportion of patients with best objective response being complete response (CR) or partial response (PR).

    Measured: Response was monitored continuously, with assessments every 6 weeks for 3 visits, then every 12 weeks, 4 weeks post-discontinuation, every 12 weeks until progression, and every 24 weeks until death, over an average of 16.2 months.

Timeline

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

  1. First posted26 May 2016 (estimated)
  2. Study start11 Nov 2016
  3. Primary completion11 Oct 2024
  4. Study completion11 Oct 2024

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 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
520 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02784171
Sponsor's protocol ID
I227
Other IDs
2016-002286-60, IFCT-1901, 2016
Status last verified
Dec 2024
First submitted
24 May 2016
Last updated
10 Dec 2024
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Chu Q, Perrone F, Greillier L, Tu W, Piccirillo MC, Grosso F, Lo Russo G, Florescu M, Mencoboni M, Morabito A, Cecere FL, Ceresoli GL, Dawe DE, Zucali PA, Pagano M, Goffin JR, Sanchez ML, Gridelli C, Zalcman G, Quantin X, Westeel V, Gargiulo P, Delfanti S, Tu D, Lee CW, Leighl N, Sederias J, Brown-Walker P, Luo Y, Lantuejoul S, Tsao MS, Scherpereel A, Bradbury P, Laurie SA, Seymour L. Pembrolizumab plus chemotherapy versus chemotherapy in untreated advanced pleural mesothelioma in Canada, Italy, and France: a phase 3, open-label, randomised controlled trial. Lancet. 2023 Dec 16;402(10419):2295-2306. doi: 10.1016/S0140-6736(23)01613-6. Epub 2023 Nov 3.

    PubMed 37931632

  • Uprety D. CheckMate 743: A Glimmer of Hope for Malignant Pleural Mesothelioma. Clin Lung Cancer. 2021 Mar;22(2):71-73. doi: 10.1016/j.cllc.2020.11.009. Epub 2020 Dec 2. No abstract available.

    PubMed 33358660

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Cisplatin, Pemetrexed and Pembrolizumab in people with Mesothelioma, run by Canadian Cancer Trials Group at 57 sites in 3 countries.

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 32 inclusion and 17 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 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 57 sites in France, Italy, Canada. 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 combined 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.

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?

Yes. Results are posted in the registry (first posted 10 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Phase II: Progression Free Survival Measured as Time From Randomization to First Observation of Objective Disease Relapse or Progression (time frame: PFS was monitored continuously, with assessments every 6 weeks for 3 visits, then every 12 weeks, 4 weeks post-discontinuation, every 12 weeks until progression, and every 24 weeks until death, over an average of 16.2 months.). 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 NCT02784171, 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 Dec 2024.

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