Pembrolizumab in Patients With Advanced Malignant Pleural Mesothelioma

Mesothelioma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02784171
• Other study ID #: I227
• Secondary ID: 2016-002286-60IF
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: November 11, 2016
• Est. completion date: June 30, 2024

Study information

• Verified date: August 2023
• Source: Canadian Cancer Trials Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 520
• Est. completion date: June 30, 2024
• Est. primary completion date: April 24, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Mesothelioma
• Mesothelioma, Malignant

Intervention

Drug:
• Cisplatin

• Pemetrexed

• Pembrolizumab

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario
Canada	BCCA - Cancer Centre for the Southern Interior	Kelowna	British Columbia
Canada	London Regional Cancer Program	London	Ontario
Canada	CHUM-Centre Hospitalier de l'Universite de Montreal	Montreal	Quebec
Canada	The Research Institute of the McGill University	Montreal	Quebec
Canada	Ottawa Hospital Research Institute	Ottawa	Ontario
Canada	University Institute of Cardiology and	Quebec City	Quebec
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	BCCA - Fraser Valley Cancer Centre	Surrey	British Columbia
Canada	University Health Network	Toronto	Ontario
Canada	CancerCare Manitoba	Winnipeg	Manitoba
France	CHU - Angers	Angers
France	Hopital Jean Minjoz	Besancon Cedex
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	Creteil
France	Centre Hospitalier du Mans	Le Mans
France	Lille - Hopital Calmette	Lille
France	CHU Dupuytren	Limoges	FR
France	Hopital du Scorff	Lorient	FR
France	Marseille - Hopital Nord	Marseille
France	Centre Hospitalier de Mulhouse	Mulhouse
France	Centre Rene Gauducheau	Nantes
France	AP-HP Hopital Tenon	Paris	Cedex 20
France	Hopital Bichat	Paris
France	Lyon URCOT	Pierre-benite	FR
France	CHU Rennes - Hopital Pontchaillou	Rennes	FR
France	Nouvel Hopital Civil Hopitaux	Strasbourg
France	CHITS Toulon Sainte Musse	Toulon
France	Hopital Larrey	Toulouse
France	CHRU de Tours - Hopital Bretonneau	Tours Cedex	Tours Cedex 9
France	Centre Alexis Vautrin	Vandoeuvre les Nancy	Cedex
France	Institut Gustave-Roussy	Villejuif	FR
Italy	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	PO A Perrino ASL Brindisi - UOC Oncologia Medica	Brindisi
Italy	AOU Policlinico Vittorio Emanuele UOC di Oncologia	Catania
Italy	Azienda Ospedaliera Garibaldi Nesima	Catania	CT
Italy	U.O. di Oncologia Ospedale Villa Scassi	Genova
Italy	Intstituto Scientifico Romangnolo	Meldola
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano
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	Oncologia Medica IRCCS Arcispedale Maria	Reggio Emilia	RE
Italy	Istituti Fisioterapici Ospitalieri IFO Istituto	Rome	RM
Italy	Instituto Clinico Humanitas	Rozzano (MI)	Lombardia

Sponsors (4)

Lead Sponsor	Collaborator
Canadian Cancer Trials Group	Intergroupe Francophone de Cancerologie Thoracique, Merck Sharp & Dohme LLC, National Cancer Institute, Naples

Countries where clinical trial is conducted

Canada,  France,  Italy, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase II: Progression free survival measured as time from randomization to first observation of objective disease relapse or progression		32 months
Primary	Phase III: Overall Survival defined as time from randomization to the date of death from any cause		32 months
Secondary	Number and severity of adverse events		32 months
Secondary	Overall Survival		32 months
Secondary	Quality of Life using EORTC QLQ-C30		32 months
Secondary	Objective Response rate compared using Fisher's exact test		32 months