Intrapleural Photodynamic Therapy in a Multimodal Treatment for Patients With Malignant Pleural Mesothelioma (MesoPDT)

Primary Outcome Measures

• Number of Patients having the full multimodal treatment without unacceptable and unexpected toxicities (grade ≥ 3) graded According to NCI CTC Version 4.0 [ Time Frame: at 12 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures

• Number of responders or stable patients after surgery [ Time Frame: at 12 months ] [ Designated as safety issue: Yes ]
• Progression-free survival (PFS) [ Time Frame: through study completion, an average of 13 months ] [ Designated as safety issue: Yes ]
• Quality of life assessed by a specific questionnaire MPM (HCCA EORTC-30) [ Time Frame: Baseline and at 12 months ] [ Designated as safety issue: Yes ]

Detailed Description

phase II trial assessing the feasibility of an experimental multimodal treatment combining:
• surgery of the MPM: extended pleurectomy/decortication (eP/D)
• intra-operative (intrapleural) photodynamic therapy (PDT). Briefly, each patient will receive porfimer sodium (PHOTOFRIN®) (2 mg/kg) 24 hours before eP/D (IV injection on 3-5 minutes). Cutaneous light precautions will be instituted immediately and for the next 4 weeks.
• then:
• prophylactic chest radiotherapy of surgical scars to prevent tumor seeding (3 x 7 Gray)
• adjuvant standard chemotherapy by (cis)platin 75 mg/m2 and pemetrexed 500 mg/m2 up to 6 cycles (1 cycle every 3 weeks), with oral folic acid (400 μg daily) and vitamin B12 (1000 μg Q9W) supplementation
• follow-up

Eligibility

Inclusion Criteria

histologically-proved epithelioid malignant pleural mesothelioma (MPM) on biopsies obtained before eP/D surgery

tumor stage: no tumor extension to controlateral lung, mediastinum, peritoneum or myocardium (<T4); mediastinal lymph nodes extension: cN2 but no bulky N2 or N3), no metastasis (M0)

Performance status WHO PS 0-1

patients fit to have surgery (eP/D) and chemotherapy (cisplatin-pemetrexed), based on clinical examination, complete normal biological work-up, full assessment by cardiac and pulmonary function tests. Predicted post-surgical values should be sufficient for normal daily life: FEV1>40%; pre-surgical DLCO>50% predicted value and VO2max >15 ml/min/kg; (left ventricular) cardiac function >50% and no significant pulmonary artery hypertension

written informed consent must be obtained before inclusion and randomization

Exclusion Criteria

Another histologic subtype than epithelioid MPM at the time of diagnosis

Bulky N2, N3 and/or M1 stage (UICC/IMIG 1995)

prior chemotherapy for mesothelioma

prior radiotherapy of thorax, neck or upper abdomen

other malignancy treated within 5 years, except basal cell carcinoma or in situ carcinoma of the cervix

contra-indication for MPM surgery or chemotherapy (cisplatin and pemetrexed): cardiac failure, pulmonary hypertension, liver or kidney dysfunction (GFR<60 ml/min), uncontrolled infection, previous major neurotoxicity or ototoxicity,… or other severe condition according to the investigator

pregnancy or breast feeding

contra-indication for porfimer sodium (Photofrin): porphyria or known hypersensitivity to porphyrins, severe hepatic impairment, tracheo-oesophageal or broncho-oesophageal fistula, suspected erosion of major blood vessels due to risk of massive, potentially fatal haemorrhage

A previous talc pleurodesis during diagnostic thoracoscopy is NOT an exclusion criteria but talc on mediastinal pleura should be avoided to not keep away from eP/D.