Pembrolizumab in Patients With Advanced Malignant Pleural Mesothelioma

NCT02784171 | Completed Phase 2 Results DMC

• 3 other identifiers: I2272016-002286-60IFCT-1901
• Study Type: interventional
• Target: 520
• Locations: 3 countries
• Sites: 57

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.

Conditions

Mesothelioma

Outcome Measures

Primary Outcomes (2)

• 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).

  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.

• 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 .

  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)

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

  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.

• Phase III: Objective Response Rate

  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.

Study Arms (3)

Arm A - Cisplatin/Pemetrexed

ACTIVE COMPARATOR

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

Drug: Cisplatin; Drug: Pemetrexed

Arm B - Cisplatin/Pemetrexed/Pembrolizumab

ACTIVE COMPARATOR

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

Drug: Cisplatin; Drug: Pemetrexed; Drug: Pembrolizumab

Arm C - Pembrolizumab (Phase II only)

ACTIVE COMPARATOR

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

Drug: Pembrolizumab

Interventions

Cisplatin DRUG

Arm A - Cisplatin/Pemetrexed; Arm B - Cisplatin/Pemetrexed/Pembrolizumab

Pemetrexed DRUG

Arm A - Cisplatin/Pemetrexed; Arm B - Cisplatin/Pemetrexed/Pembrolizumab

Pembrolizumab DRUG

Arm B - Cisplatin/Pemetrexed/Pembrolizumab; Arm C - Pembrolizumab (Phase II only)

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 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:

You may not qualify if:

• 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.

Sponsors & Collaborators

• Canadian Cancer Trials Group: lead
• National Cancer Institute, Naples: collaborator
• Merck Sharp & Dohme LLC: collaborator
• Intergroupe Francophone de Cancerologie Thoracique: collaborator

Study Sites (57)

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

BCCA - Cancer Centre for the Southern Interior

Kelowna, British Columbia, V1Y 5L3, Canada

Location

BCCA - Fraser Valley Cancer Centre

Surrey, British Columbia, V3V 1Z2, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

London Regional Cancer Program

London, Ontario, N6A 5W9, Canada

Location

Ottawa Hospital Research Institute

Ottawa, Ontario, K1H 8L6, Canada

Location

University Health Network

Toronto, Ontario, M5G 2M9, Canada

Location

CHUM-Centre Hospitalier de l'Universite de Montreal

Montreal, Quebec, H2X 3E4, Canada

Location

The Research Institute of the McGill University

Montreal, Quebec, H4A 3J1, Canada

Location

University Institute of Cardiology and

Québec, Quebec, G1V 4G5, Canada

Location

Allan Blair Cancer Centre

Regina, Saskatchewan, S4T 7T1, Canada

Location

AP-HP Hopital Tenon

Paris, Cedex 20, 75970, France

Location

Centre Alexis Vautrin

Vandœuvre-lès-Nancy, Cedex, 54500, France

Location

CHU Dupuytren

Limoges, FR, 87042, France

Location

Hopital du Scorff

Lorient, FR, 56100, France

Location

Lyon URCOT

Pierre-Bénite, FR, 69310, France

Location

CHU Rennes - Hopital Pontchaillou

Rennes, FR, 35033, France

Location

Institut Gustave-Roussy

Villejuif, FR, 94805, France

Location

CHRU de Tours - Hopital Bretonneau

Tours, Tours Cedex 9, 37044, France

Location

CHU - Angers

Angers, 49033, France

Location

Hopital Jean Minjoz

Besançon, 25030, France

Location

Institut Bergonie

Bordeaux, 33076, France

Location

Boulogne - Ambroise Pare

Boulogne, 92104, France

Location

Caen - CHU

Caen, 14000, France

Location

Clermont-Ferrand - CHU

Clermont-Ferrand, 63003, France

Location

Centre Hospitalier Intercommunal de Creteil

Créteil, 94000, France

Location

Centre Hospitalier du Mans

Le Mans, 72037, France

Location

Lille - Hopital Calmette

Lille, 59037, France

Location

Marseille - Hopital Nord

Marseille, 13915, France

Location

Unknown Facility

Montpellier, CEDEX 5, France

Location

Centre Hospitalier de Mulhouse

Mulhouse, 68070, France

Location

Centre Rene Gauducheau

Nantes, 44805, France

Location

Hopital Bichat

Paris, 75877, France

Location

Nouvel Hopital Civil Hopitaux

Strasbourg, 67091, France

Location

CHITS Toulon Sainte Musse

Toulon, 83056, France

Location

Hopital Larrey

Toulouse, 31059, France

Location

Oncologia SS Antonio e Biagio Alessandria

Alessandria, AL, 15121, Italy

Location

Azienda Ospedaliera San Giuseppe Moscati

Avellino, AV, 83100, Italy

Location

IRCCS Ospedale Oncologico Giovanni Paolo II

Bari, BA, 70124, Italy

Location

Oncologia Medica Humanitas Gavazzeni Bergamo

Bergamo, BG, 24125, Italy

Location

Azienda Ospedaliera Garibaldi Nesima

Catania, CT, 95123, Italy

Location

Instituto Clinico Humanitas

Rozzano (MI), Lombardy, 20089, Italy

Location

Oncologia Medica IRCCS Arcispedale Maria

Reggio Emilia, RE, 42123, Italy

Location

Istituti Fisioterapici Ospitalieri IFO Istituto

Rome, RM, 00144, Italy

Location

PO A Perrino ASL Brindisi - UOC Oncologia Medica

Brindisi, 72100, Italy

Location

AOU Policlinico Vittorio Emanuele UOC di Oncologia

Catania, 95125, Italy

Location

U.O. di Oncologia Ospedale Villa Scassi

Genova, 16149, Italy

Location

Intstituto Scientifico Romangnolo

Meldola, 47014, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

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

Mirano, 30035, Italy

Location

Azienda Ospedaliera di Rilievo Nazionale

Napoli, 80131, Italy

Location

Dott. Fortunato Ciardiello,Cattedra Oncologia Medica

Napoli, 80131, Italy

Location

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

Napoli, 80131, Italy

Location

Unita Sperimentazioni Cliniche Istituto per lo

Napoli, 80131, Italy

Location

Azienda USL di Piacenza, Ospedale Gugliemimo Salieto

Piacenza, 29100, Italy

Location

Related Publications (2)

• 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.

  PMID: 37931632 RESULT

• 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.

  PMID: 33358660 DERIVED

MeSH Terms

Conditions

Mesothelioma

Interventions

Cisplatin; Pemetrexed; pembrolizumab

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Results Point of Contact

• Title: Dr. Lesley Seymour
• Organization: Canadian Cancer Trials Group

lseymour@ctg.queensu.ca

613533600

Study Officials

• Quincy Chu

  Cross Cancer Institute, Edmonton Alberta Canada

  STUDY CHAIR

• Francesco Perrone

  National Cancer Institute of Naples, Italy

  STUDY CHAIR

• Laurent Greillier Marseille

  Hopital Nord, France

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: May 24, 2016
• First Posted: May 26, 2016
• Study Start: November 11, 2016
• Primary Completion: October 11, 2024
• Study Completion: October 11, 2024
• Last Updated: December 10, 2024
• Results First Posted: December 10, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

IT (19); CA (13); FR (25)