Clinical trial NCT02436733: Pleurectomy/ Decortication (P/D) Preceded or Followed by Chemotherapy in Patients With Early Stage MPM
Official title: EORTC Randomized Phase II Study of Pleurectomy/ Decortication (P/D) Preceded or Followed by Chemotherapy in Patients With Early Stage Malignant Pleural Mesothelioma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Malignant Pleural Mesothelioma
Keywords: pleural mesothelioma
phase II
randomized
surgery
chemotherapy
feasibility
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2015-05-07
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Primary outcomes:
measure: Rate of success to complete the full treatment
timeFrame: 20weeks
Secondary outcomes:
measure: Loco-regional failure free survival
timeFrame: 6 months
measure: Overall survival
timeFrame: 15 months
measure: Treatment side-effects
timeFrame: 36 weeks
Other outcomes:
Locations:
city: Antwerpen
country: Belgium
facility: UZ Antwerpen
city: Gent
country: Belgium
facility: UZ Gent
city: Amsterdam
country: Netherlands
facility: The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis
city: Rotterdam
country: Netherlands
facility: Erasmus MC Hospital
Study officials:
affiliation: UZ Antwerpen, Belgium
name: Jan Van Meerbeeck, Pr.
role: PRINCIPAL_INVESTIGATOR
References: