Pleurectomy/ Decortication (P/D) Preceded or Followed by Chemotherapy in Patients With Early Stage MPM

NCT ID: NCT02436733

Last Updated: 2022-11-07

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-20
• Study Completion Date: 2023-09-30

Brief Summary

This is a multicenter, randomized, 1:1, non-comparative phase II trial. Patients with early stage MPM will be randomized between Arm A: immediate P/D followed by three cycles of chemotherapy (pemetrexed 500mg/m2 and cisplatin 75 mg/m2, both drugs given on day 1, every three weeks) Arm B: three cycles of chemotherapy (same regimen) followed by P/D, for non-progressing patients

Detailed Description

This is an academic led, multicenter, randomized, 1:1, non-comparative phase II trial. Patients with early stage MPM will be randomized between

• Arm A - immediate surgery: immediate P/D followed by three cycles of chemotherapy (pemetrexed 500mg/m2 and cisplatin 75 mg/m2, both drugs given on day 1, every three weeks) for non-progressing patients
• Arm B - delayed surgery: three cycles of chemotherapy (same regimen) followed by P/D, for non-progressing patients.

A maximum of four weeks (±2 weeks) will be allowed between the baseline tumor assessment and the start of treatment (surgery or chemotherapy). Randomization should be done as soon as possible after baseline tumor assessment.

The primary objective of the study is to investigate the feasibility of immediate P/D followed by cisplatin/pemetrexed chemotherapy or deferred P/D after cisplatin/pemetrexed chemotherapy in patients with early stage MPM.

The results of this study will allow the LCG to take one of the arms further to a comparative study with either no surgery or EPP as control arm. The choice of the comparator will depend on the result of a parallel ongoing randomized study in the UK, comparing P/D with no surgery

Conditions

Malignant Pleural Mesothelioma

Study Design

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

Study Groups

Immediate pleurectomy/decortication

immediate P/D followed by three cycles of pemetrexed 500mg/m2 IV and cisplatin 75 mg/m2 IV, both drugs given on day 1, every three weeks for non-progressing patients

Group Type: EXPERIMENTAL

pleurectomy/decortication

Intervention Type: PROCEDURE

Lung sparing procedures consist of the resection of the pleura without removing the lung

Pemetrexed/Cisplatin

Intervention Type: DRUG

On day 1 of each cycle, pemetrexed 500 mg/m2 should be administered as IV infusion followed by cisplatin 75 mg/m2 as IV.

Delayed pleurectomy/decortication

three cycles of pemetrexed 500mg/m2 IV and cisplatin 75 mg/m2 IV, both drugs given on day 1, every three weeks followed by P/D, for non-progressing patients.

Group Type: ACTIVE_COMPARATOR

pleurectomy/decortication

Intervention Type: PROCEDURE

Lung sparing procedures consist of the resection of the pleura without removing the lung

Pemetrexed/Cisplatin

Intervention Type: DRUG

On day 1 of each cycle, pemetrexed 500 mg/m2 should be administered as IV infusion followed by cisplatin 75 mg/m2 as IV.

Interventions

pleurectomy/decortication

Lung sparing procedures consist of the resection of the pleura without removing the lung

Intervention Type: PROCEDURE

Pemetrexed/Cisplatin

On day 1 of each cycle, pemetrexed 500 mg/m2 should be administered as IV infusion followed by cisplatin 75 mg/m2 as IV.

Intervention Type: DRUG

Other Intervention Names

P/D; CisPem

Eligibility Criteria

Inclusion Criteria

• Patients aged 18 years or older, with pathologically proven malignant pleural mesothelioma. All histological subtypes are accepted.
• Stage cT1-3, N0-2, M0 according to UICC TNM classification. FDG-PET-CT scan showing absence of M1, N3, supraclavicular and coeliac node involvement is required. No clinical invasion of mediastinal structures (heart, aorta, spine, esophagus, etc.) and no widespread chest wall invasion (T4) are acceptable. Focal chest wall lesions are acceptable.
• No prior treatment of any kind for mesothelioma is allowed, especially prophylactic track irradiation after diagnostic procedures.
• WHO performance status 0-1
• Fit to receive chemotherapy and undergo a pleurectomy/ decortication with optional removal of hemidiaphragm and pericardium.
• No history of other malignancy within the last three years, except for carcinoma in situ of the cervix or basal cell or spinocellular carcinoma of the skin.
• No pre-existing peripheral sensory or motor neuropathy > grade I according to CTCAE v4.0
• No clinically significant pleural effusion that cannot be managed with thoracentesis or pleurodesis (according to institutional practice). If pleurodesis is considered, it should be done before randomization.
• Adequate organ function Women of child bearing potential must have a negative serum (or urine) pregnancy test within 3 days prior to the start of chemotherapy/surgery. Patients of childbearing / reproductive potential should use adequate birth control measures, as defined by the investigator, during the study treatment period and for at least three months after the last study treatment.

Before patient registration written informed consent must be given according to ICH/GCP, and national/local regulations.

Exclusion Criteria

• Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound healing disorders; ulcers; or bone fractures, known infection with HIV, active hepatitis B and/or hepatitis C virus).

significant cardiovascular morbidity (assessed by cardiologist) precluding surgery

• Major surgical procedure or significant traumatic injury within 28 days prior to randomization or anticipation of the need for major surgery (other than P/D) during the course of study treatment.
• History of receiving any investigational treatment within 28 days of randomization.
• History of intolerance to pemetrexed and/or cisplatin.
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jan Van Meerbeeck, Pr.

Role: PRINCIPAL_INVESTIGATOR

UZ Antwerpen, Belgium

Locations

UZ Antwerpen

Antwerp, , Belgium

UZ Gent

Ghent, , Belgium

The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis

Amsterdam, , Netherlands

Erasmus MC Hospital

Rotterdam, , Netherlands

Countries

Belgium; Netherlands

Other Identifiers

EORTC-1205

Identifier Type: -

Identifier Source: org_study_id