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

Primary Purpose

Malignant Pleural Mesothelioma

Status

Completed

Phase

Phase 2

Locations

France

Study Type

Interventional

Intervention

photodynamic therapy (PDT)

thoracic surgery Pleurectomy / extended Decortication

Adjuvant chemotherapy

About this trial

This is an interventional treatment trial for Malignant Pleural Mesothelioma focused on measuring mesothelioma, multimodal treatment, PDT, pleura

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

CHRU de Lille Hôpital Calmette

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

multimodal treatment + intrapleural PDT

Arm Description

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

Outcomes

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

Secondary Outcome Measures

Number of responders or stable patients after surgery

Progression-free survival (PFS)

Quality of life assessed by a specific questionnaire MPM (HCCA EORTC-30)

Full Information

NCT ID

NCT02662504

First Posted

January 14, 2016

Last Updated

June 12, 2018

Sponsor

University Hospital, Lille

Collaborators

Institut National de la Santé Et de la Recherche Médicale, France, University of Pennsylvania, Région Nord-Pas de Calais, France

1. Study Identification

Unique Protocol Identification Number

NCT02662504

Brief Title

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

Acronym

MesoPDT

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2017

Overall Recruitment Status

Completed

Study Start Date

January 16, 2016 (Actual)

Primary Completion Date

March 12, 2018 (Actual)

Study Completion Date

March 13, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Hospital, Lille

Collaborators

Institut National de la Santé Et de la Recherche Médicale, France, University of Pennsylvania, Région Nord-Pas de Calais, France

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Malignant Pleural Mesothelioma

Keywords

mesothelioma, multimodal treatment, PDT, pleura

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

6 (Actual)

8. Arms, Groups, and Interventions

Arm Title

multimodal treatment + intrapleural PDT

Arm Type

Experimental

Arm Description

Intervention Type

Device

Intervention Name(s)

photodynamic therapy (PDT)

Other Intervention Name(s)

Photofrin

Intervention Description

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.

Intervention Type

Procedure

Intervention Name(s)

thoracic surgery Pleurectomy / extended Decortication

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Adjuvant chemotherapy

Other Intervention Name(s)

pemetrexed / cisplatin

Intervention Description

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.

Primary Outcome Measure Information:

Title

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

Secondary Outcome Measure Information:

Title

Number of responders or stable patients after surgery

Time Frame

at 12 months

Title

Progression-free survival (PFS)

Time Frame

through study completion, an average of 13 months

Title

Quality of life assessed by a specific questionnaire MPM (HCCA EORTC-30)

Time Frame

Baseline and at 12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Arnaud Scherpereel, MD, PhD

Organizational Affiliation

University Hospital, Lille

Official's Role

Principal Investigator

Facility Information:

Facility Name

CHRU de Lille Hôpital Calmette

City

Lille

Country

France

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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