The IMmunotherapy Pleural 5-ALA PDT

Официальное название

Intrapleural Photodynamic Therapy by Video-Assisted Thoracoscopy Followed by Anti-PD-1 NIVOLUMAB in Patients With Malignant Pleural Mesothelioma - a Pilot Study

Обзор

Pilot study of the feasibility of an innovative multimodal treatment combining intrapleural photodynamic therapy with videothoracoscopy followed by adjuvant immunotherapy with anti-PD-1 Nivolumab antibodies in patients with malignant pleural mesothelioma

Вмешательства

• Устройство intrapleural photodynamic therapy with videothoracoscopy
  MPM patients will be first administrated 20 mg/kg of oral photosensitizer, 5-Aminolevulinic Acid (5-ALA) {Gliolan®}, 4 to 6 hours prior undergoing thoracoscopy (VATS). During VATS procedure, after a qualitative control of the fluorescence of tumor lesions and some guided pleural tumor biopsies, the pleural cavity will be illuminated using a flexible probe and laser source at a specific wavelength for 5-ALA (400-500 nm; 25 J/cm2) during 15 minutes (6 fractions of 2.5 minutes separated by 5 pauses
• Препарат Nivolumab Injection
  Seven to 10 days after VATS, patients will start to be treated by Nivolumab 240mg IV every 2 weeks till progression (CT-scan reassessment every 8 cycles), unacceptable toxicity, or maximum 2 years.

Первичные конечные точки

• the proportion of patients having the full multimodal treatment [Срок оценки: through study completion, an average of 24 months]

Вторичные конечные точки (5)

• objective response rate (ORR) according to modified RECIST 1.1 criteria for mesothelioma for pleural lesions; RECIST 1.1 for all other targets [Срок оценки: through study completion, an average of 24 months]
• Kaplan Meier curve for overall survival (mOS) [Срок оценки: through study completion, an average of 24 months]
• Kaplan Meier curve for progression free survival (mPFS) [Срок оценки: through study completion, an average of 24 months]
• quality of life (QoL) of patients by dedicated EORTC QLQ C30 (or LCSS-30) questionnaire [Срок оценки: At baseline and]
• evaluation of chest pain using visual scale. [Срок оценки: through study completion, an average of 24 months]

Критерии участия

Критерии включения

• ECOG Performance status (PS) 0-1 (WHO)
• Unresectable Malignant Pleural Mesothelioma
• suffering from unresectable MPM (n=20), relapsing after one or 2 lines of treatment with platinum-based doublet of chemotherapy (including pemetrexed) \[Note: MPM patients having contra-indications for, or refusing chemotherapy may also be recruited\], and candidate for palliative pleural procedure (i.e. thoracoscopy for pleurodesis by talc or by insertion of indwelled pleural catheter, IPC)
• Documented progression after previous 1 or 2 lines of chemotherapy including Platinum/Pemetrexed chemotherapy\*
• Measurable disease according to modified RECIST 1.1. for MPM
• Malignant pleural lesion assessed to be accessible by local PDT treatment during thoracoscopy, as validated by expert MTB ("MESOCLIN", Lille, France)
• Histological diagnosis confirmed by national expert pathology panel ("MESOPATH" - Institut Léon Bérard, Lyon, France)
• Weight loss <10%
• available tumor tissue (archival or fresh)
• obtention of an informed written consent before any specific procedure of the study
• Decision to treat the patient within this clinical trial taken during MPM dedicated multidisciplinary board (RCP MESOCLIN in France )
• Patient affiliated to and covered by social security for standard care
• Women of child-bearing potential must use a highly effective method of contraception for 28 days prior to the first dose of investigational product, and must agree to continue using such precautions for 5 months after the final dose of investigational product
• Women of child-bearing potential must have a negative pregnancy test within 24h before administration of investigational product
• First line patients may also be recruited if they declined or if they have contra-indications for chemotherapy.

Критерии исключения

• lack of informed written consent; or refusal to sign or to participate
• Pregnant, breastfeeding patients, and female patients of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in the protocol for the duration of the study and for at least 5 months after the last dose of nivolumab
• Male patients who are unwilling or unable to use contraception methods for the duration of the study and for at least 7 months after the last dose of nivolumab
• a previous treatment by anti-PD-1 or anti-PD-L1 antibodies for their cancer or any other cancer in the last 5 years
• hypersensitivity to Nivolumab (anti-PD-1 antibodies)
• contra-indications for 5-ALA or PDT
• contra-indications for thoracoscopy (VATS)
• any other comorbidity precluding the feasibility of the therapeutic protocol: uncontrolled cardiac failure, pulmonary hypertension, liver or kidney severe dysfunction (creatinin clearance <60 ml/min), uncontrolled infection, or other disease according to the investigator
• other cancer treated within 5 years before inclusion except baso-cellular skin carcinoma or cervical / bladder in situ carcinoma
• inability to receive study information and to give informed consent
• patient unable to have a clinical follow-up due to psychological, familial, social or geographical reasons
• legal incapacity (people in jail), or under supervision (i.e. guardianship or curatorship)
• treatment with experimental drug within 30 days before the start of the study

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Франция · 1 центр

• Institut Coeur-Poumon, CHU — Lille

Идентификаторы

NCT: NCT04400539 · 2019_41 · 2019-003003-35

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗