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

NCT02436733 | Unknown Phase 2 DMC

• 1 other identifier: EORTC-1205
• Study Type: interventional
• Target: 64
• Locations: 2 countries
• Sites: 4

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

Conditions

Malignant Pleural Mesothelioma

Keywords

pleural mesothelioma; phase II; randomized; surgery; chemotherapy; feasibility

Outcome Measures

Primary Outcomes (1)

• Rate of success to complete the full treatment

  A patient is considered to be a "treatment success" if he/she meets all of the following criteria: 1. Patient has received the full protocol treatment, defined as 3 cycles of pemetrexed and cisplatin (allowing for the dose adjustments described in section 5.3), preceded/followed by pleurectomy/decortication (P/D) (as described in section 5.3). 2. Patient alive and has no evidence of progression/relapse at week 20 (±2 weeks) after the first day of starting protocol treatment (either chemotherapy or P/D). 3. Patient has no persisting grade 3-4 treatment side-effects (CTCAE V 4.0) at week 20 (±2 weeks) after the first day of starting protocol treatment (either chemotherapy or P/D)

  20weeks

Secondary Outcomes (3)

• Loco-regional failure free survival

  6 months

• Overall survival

  15 months

• Treatment side-effects

  36 weeks

Study Arms (2)

Immediate pleurectomy/decortication

EXPERIMENTAL

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

Procedure: pleurectomy/decortication; Drug: Pemetrexed/Cisplatin

Delayed pleurectomy/decortication

ACTIVE COMPARATOR

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.

Procedure: pleurectomy/decortication; Drug: Pemetrexed/Cisplatin

Interventions

pleurectomy/decortication PROCEDURE

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

Also known as: P/D

Delayed pleurectomy/decortication; Immediate pleurectomy/decortication

Pemetrexed/Cisplatin 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.

Also known as: CisPem

Delayed pleurectomy/decortication; Immediate pleurectomy/decortication

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead

Study Sites (4)

UZ Antwerpen

Antwerp, Belgium

Location

UZ Gent

Ghent, Belgium

Location

The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis

Amsterdam, Netherlands

Location

Erasmus MC Hospital

Rotterdam, Netherlands

Location

MeSH Terms

Conditions

Mesothelioma, Malignant

Interventions

Cerebral Decortication; Pemetrexed; Cisplatin

Condition Hierarchy (Ancestors)

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Neurosurgical Procedures; Surgical Procedures, Operative; 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; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Jan Van Meerbeeck, Pr.

  UZ Antwerpen, Belgium

  PRINCIPAL INVESTIGATOR

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: April 21, 2015
• First Posted: May 7, 2015
• Study Start: September 20, 2016
• Primary Completion: July 1, 2023
• Study Completion: September 1, 2023
• Last Updated: November 7, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

NL (2); BE (2)