Pembrolizumab in Patients With Advanced Malignant Pleural Mesothelioma

NCT ID: NCT02784171

Last Updated: 2024-12-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 520 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-11
• Study Completion Date: 2024-10-11

Brief 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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A - Cisplatin/Pemetrexed

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

Group Type: ACTIVE_COMPARATOR

Cisplatin

Intervention Type: DRUG

Pemetrexed

Intervention Type: DRUG

Arm B - Cisplatin/Pemetrexed/Pembrolizumab

Pembrolizumab 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

Group Type: ACTIVE_COMPARATOR

Cisplatin

Intervention Type: DRUG

Pemetrexed

Intervention Type: DRUG

Pembrolizumab

Intervention Type: DRUG

Arm C - Pembrolizumab (Phase II only)

Pembrolizumab 200 mg\* IV 30 min Day 1 every 21 days for a total of 2 years

Group Type: ACTIVE_COMPARATOR

Pembrolizumab

Intervention Type: DRUG

Interventions

Cisplatin

Intervention Type: DRUG

Pemetrexed

Intervention Type: DRUG

Pembrolizumab

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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
• 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.

Exclusion Criteria

• 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.
• 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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute, Naples

OTHER

Sponsor Role: collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Intergroupe Francophone de Cancerologie Thoracique

OTHER

Sponsor Role: collaborator

Canadian Cancer Trials Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Quincy Chu

Role: STUDY_CHAIR

Cross Cancer Institute, Edmonton Alberta Canada

Francesco Perrone

Role: STUDY_CHAIR

National Cancer Institute of Naples, Italy

Laurent Greillier Marseille

Role: STUDY_CHAIR

Hopital Nord, France

Locations

Tom Baker Cancer Centre

Calgary, Alberta, Canada

Cross Cancer Institute

Edmonton, Alberta, Canada

BCCA - Cancer Centre for the Southern Interior

Kelowna, British Columbia, Canada

BCCA - Fraser Valley Cancer Centre

Surrey, British Columbia, Canada

CancerCare Manitoba

Winnipeg, Manitoba, Canada

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, Canada

London Regional Cancer Program

London, Ontario, Canada

Ottawa Hospital Research Institute

Ottawa, Ontario, Canada

University Health Network

Toronto, Ontario, Canada

CHUM-Centre Hospitalier de l'Universite de Montreal

Montreal, Quebec, Canada

The Research Institute of the McGill University

Montreal, Quebec, Canada

University Institute of Cardiology and

Québec, Quebec, Canada

Allan Blair Cancer Centre

Regina, Saskatchewan, Canada

AP-HP Hopital Tenon

Paris, Cedex 20, France

Centre Alexis Vautrin

Vandœuvre-lès-Nancy, Cedex, France

CHU Dupuytren

Limoges, FR, France

Hopital du Scorff

Lorient, FR, France

Lyon URCOT

Pierre-Bénite, FR, France

CHU Rennes - Hopital Pontchaillou

Rennes, FR, France

Institut Gustave-Roussy

Villejuif, FR, France

CHRU de Tours - Hopital Bretonneau

Tours, Tours Cedex 9, France

CHU - Angers

Angers, , France

Hopital Jean Minjoz

Besançon, , France

Institut Bergonie

Bordeaux, , France

Boulogne - Ambroise Pare

Boulogne, , France

Caen - CHU

Caen, , France

Clermont-Ferrand - CHU

Clermont-Ferrand, , France

Centre Hospitalier Intercommunal de Creteil

Créteil, , France

Centre Hospitalier du Mans

Le Mans, , France

Lille - Hopital Calmette

Lille, , France

Marseille - Hopital Nord

Marseille, , France

Montpellier, , France

Centre Hospitalier de Mulhouse

Mulhouse, , France

Centre Rene Gauducheau

Nantes, , France

Hopital Bichat

Paris, , France

Nouvel Hopital Civil Hopitaux

Strasbourg, , France

CHITS Toulon Sainte Musse

Toulon, , France

Hopital Larrey

Toulouse, , France

Oncologia SS Antonio e Biagio Alessandria

Alessandria, AL, Italy

Azienda Ospedaliera San Giuseppe Moscati

Avellino, AV, Italy

IRCCS Ospedale Oncologico Giovanni Paolo II

Bari, BA, Italy

Oncologia Medica Humanitas Gavazzeni Bergamo

Bergamo, BG, Italy

Azienda Ospedaliera Garibaldi Nesima

Catania, CT, Italy

Instituto Clinico Humanitas

Rozzano (MI), Lombardy, Italy

Oncologia Medica IRCCS Arcispedale Maria

Reggio Emilia, RE, Italy

Istituti Fisioterapici Ospitalieri IFO Istituto

Rome, RM, Italy

PO A Perrino ASL Brindisi - UOC Oncologia Medica

Brindisi, , Italy

AOU Policlinico Vittorio Emanuele UOC di Oncologia

Catania, , Italy

U.O. di Oncologia Ospedale Villa Scassi

Genova, , Italy

Intstituto Scientifico Romangnolo

Meldola, , Italy

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, , Italy

U.O.C. di Oncologia U.L.S.S. 13

Mirano, , Italy

Azienda Ospedaliera di Rilievo Nazionale

Napoli, , Italy

Dott. Fortunato Ciardiello,Cattedra Oncologia Medica

Napoli, , Italy

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

Napoli, , Italy

Unita Sperimentazioni Cliniche Istituto per lo

Napoli, , Italy

Azienda USL di Piacenza, Ospedale Gugliemimo Salieto

Piacenza, , Italy

Countries

Canada; France; Italy

References

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.

Reference Type: RESULT

PMID: 37931632 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33358660 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-002286-60

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

IFCT-1901

Identifier Type: OTHER

Identifier Source: secondary_id

I227

Identifier Type: -

Identifier Source: org_study_id