Intrapleural Photodynamic Therapy in a Multimodal Treatment for Patients With Malignant Pleural Mesothelioma (MesoPDT)
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|ClinicalTrials.gov Identifier: NCT02662504|
Recruitment Status : Completed
First Posted : January 25, 2016
Last Update Posted : June 14, 2018
Malignant pleural mesothelioma (MPM) is an aggressive tumour with poor prognosis (median survival <13 months), and high resistance to chemotherapy. Extended pleurectomy/decortication (eP/D) is a debulking surgery of MPM but cannot be considered as a curative treatment. Therefore it has been suggested that eP/D may be of interest if combined with intra-operative treatment and adjuvant therapies.
Photodynamic Therapy (PDT) is an innovative treatment based on the rationale that tumour cells, if previously treated with photosensitizing drugs (Photofrin), will die when exposed to light at a particular wavelength. Interestingly PDT might also stimulate anti-tumour immune response through the release of tumour antigens and induced inflammation.
PDT was tested in phase I-II trials for MPM in combination with EPP or eP/D, and chemotherapy. US studies from J Friedberg et al found very promising survival results in MPM when combining eP/D, but not EPP, intra-operative PDT and chemotherapy (cisplatin-pemetrexed), with a median overall survival of 31.7 months.
However, the definitive value of intra-pleural PDT combined to eP/D in the treatment of MPM still need to be validated. The same multimodal treatment has been established in Lille, the French national expert centre for MPM, with the help of our american colleagues. Therefore, this phase II trial proposes to patients to benefit from the combination of eP/D, intra-operative PDT then chemotherapy by cisplatin-pemetrexed and prophylactic radiotherapy.
Primary endpoint is the feasibility for the patients to have the full multimodal treatment of MPM including intrapleural PDT without unacceptable or unexpected grade III-IV toxicities. Secondary endpoints are PFS, OS, ORR, and quality of life. If the feasibility of such treatment would be confirmed in France, a multicentric, randomized trial comparing this experimental treatment vs control arm (same multimodal treatment without PDT) is planned.
|Condition or disease||Intervention/treatment||Phase|
|Malignant Pleural Mesothelioma||Device: photodynamic therapy (PDT) Procedure: thoracic surgery Pleurectomy / extended Decortication Drug: Adjuvant chemotherapy||Phase 2|
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.
- 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
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||6 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pilot Study of the Feasibility of Intrapleural Photodynamic Therapy in a Multimodal Treatment Combining Extended Pleurectomy/Decortication, Adjuvant Chemotherapy and Prophylactic Radiotherapy in Patients With Malignant Pleural Mesothelioma|
|Actual Study Start Date :||January 16, 2016|
|Actual Primary Completion Date :||March 12, 2018|
|Actual Study Completion Date :||March 13, 2018|
Experimental: multimodal treatment + intrapleural PDT
Device: photodynamic therapy (PDT)
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.
After complete macroscopic resection of the tumour, the thoracic surgeon and his team will set isoprobes (7 at least) in the "pleural" cavity to monitor by a dosimetry device the correct illumination of the cavity with a visible red light (wavelength of 630 nm; laser source). PDT-related postoperative considerations include light precautions, intensive focus on perioperative nutrition, and a greater than normal fluid requirement in the immediate postoperative period.
Other Name: Photofrin
Procedure: thoracic surgery Pleurectomy / extended Decortication
extended P/D is intended to remove any macroscopic tumor including the parietal and visceral pleura when the diaphragm and / or the pericardium was resected
Drug: Adjuvant chemotherapy
Chemotherapy should begin up to three months after surgery. It consists of pemetrexed 500 mg / m2 followed 30 minutes later by cisplatin 75 mg / m2 (in the usual manner from the center to the chemotherapy) on day 1 (J1) of each cycle every 3 weeks, for up to 6 cycles.
Other Name: pemetrexed / cisplatin
- 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 ]
- Number of responders or stable patients after surgery [ Time Frame: at 12 months ]
- Progression-free survival (PFS) [ Time Frame: through study completion, an average of 13 months ]
- Quality of life assessed by a specific questionnaire MPM (HCCA EORTC-30) [ Time Frame: Baseline and at 12 months ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02662504
|CHRU de Lille Hôpital Calmette|
|Principal Investigator:||Arnaud Scherpereel, MD, PhD||University Hospital, Lille|