Photo-induction as a Means to Improve Cisplatin Delivery to Pleural Malignancies (PDT-lipo)

Photo-induction as a Means to Improve Cisplatin Delivery to Pleural Malignancies: a Clinical Phase I Trial

This clinical study aims to explore intrapleural low-dose Visudyne®-mediated photodynamic therapy (photo-induction) as a pathway to promote the uptake of systemically administered Lipoplatin™ in pleural malignancies of patients undergoing video-assisted talcage for their malignant pleural effusions. Photo-induction is expected to overcome the chemo-resistance of pleural malignancies for cisplatin-based chemotherapeutics and thereby improve local tumor control.

Study Overview

• Status: Terminated
• Conditions: Pleural Effusion, Malignant
• Intervention / Treatment: Drug: Cisplatin, liposomal; Drug: Verteporfin; Device: Device for Intrapleural Visudyne-mediated Low-Dose Photodynamic Therapy with integrated in situ light dosimetry

Detailed Description

The primary objective of the study is to assess the safety and tolerability of intrapleural Visudyne®-mediated photo-induction as a means to selectively increase tumor uptake of systemically administered Lipoplatin™ in patients with primary or secondary pleural malignancies.

The secondary objectives are:

Assessment of treatment efficacy as measured by dyspnea reduction, pleural effusion free survival as well as local relapse rate, progression free and median overall survival.

Analysis of the pleural intratumor penetration of Lipoplatin™ by repeated biopsies for Lipoplatin concentration measurements before and after Visudyne® treatment as well as vessel modulation related parameters (pericyte coverage, vessels morphology).

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 1

Contacts and Locations

Study Locations

• Switzerland
  • Vaud (VD)
    • Lausanne, Vaud (VD), Switzerland, 1011
      • Oncology Department, Centre Hospitalier Universitaire Vaudois (CHUV)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria

• Stage IV breast, ovarian, gastric, colorectal, germ cell, lung, bladder, sarcoma or head and neck carcinoma requiring systemic chemotherapy OR alternatively
• Stage I/II malignant pleural mesothelioma OR alternatively
• Stage III/IV mesothelioma requiring systemic chemotherapy OR alternatively
• Stage IVa thymic malignancies AND
• Cytologically proven malignant pleural effusion requiring VATS pleurodesis
• PS 0-1
• Age 18-80
• Written informed content
• Life expectancy >3 months
• Laboratory Requirements - within 28 days prior to enrollment:

• Haematology:

  • absolute granulocytes ≥1× 109/L
  • platelets ≥100 × 109/L
  • leukocytes ≥3 × 109

• Biochemistry:

  • Bilirubin ≤3 × upper limit of normal (<5x if liver metastasis present)
  • AST(SGOT) ≤2.5 × upper limit of normal (<5x if liver metastasis present)
  • Creatinine clearance ≥50 mL/min according to Cockroft and Gault
• No major cardio-pulmonary co-morbidity precluding a surgical approach according to local standards
• Enrollment decision at the institutional multidisciplinary tumor board
• Patient must be willing to use effective methods of contraception. Female patients must be postmenopausal, surgically sterile, or they must agree to use a physical barrier method of contraception in addition to either an intrauterine device or hormonal contraception until at least of 3 months after the study treatment. Male patients must agree to use a barrier method (condom) for 3 months after study treatment.

Exclusion criteria

• Grade >2 peripheral neuropathy
• Any concurrent anticancer systemic therapy within 14 days before the study intervention
• Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study e.g. Known or suspected allergy to the investigational agent or any agent given in association with this trial.

Clinically serious infections requiring systemic antibiotic (e.g antiviral, antimicrobial, antifungal) therapy.

• Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
• Severe interstitial pneumonia or pulmonary fibrosis
• Chronic corticosteroid use at equivalent dose of >30mg/d methylprednisolone
• Pregnancy or breast-feeding
• Porphyria
• Severe liver insufficiency

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Lipoplatin/Visudyne-mediated photodynamic therapy; 200 mg/m2 Lipoplatin™ will be delivered as iv perfusion. Then, intrapleural photo-induction will be realized through a classical video-assisted thoracoscopic (VATS) approach using 3 mg/m2 Visudyne® activated at 689 nm. At the end of the procedure, the patients will receive chemical pleurodesis by VATS as per standard-of-care treatment for malignant pleural effusion.

Drug: Cisplatin, liposomal; Lipoplatin IV 200 mg/m2; Other Names: Lipoplatin™; Drug: Verteporfin; Visudyne® IV 3 mg/m2; Other Names: Visudyne®; Device: Device for Intrapleural Visudyne-mediated Low-Dose Photodynamic Therapy with integrated in situ light dosimetry; Intrapleural photo-induction will be realized in the chest cavity with low-dose PDT using Visudyne® 3mg/m2 as photosensitizer, activated by 689 nm laser light with a fluence of 10J/cm2 and a fluence rate of <10mWcm2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of the treatment as assessed by 30-day postoperative mortality	survival status at 30 days	30 days
Tolerability of the treatment as assessed by 30-day postoperative mortality	survival status at 30 days	30 days
Feasibility	survival status at 30 days	30 days
Acute respiratory failure rate		30-day postoperative
Dyspnea according to CTCAE v4.0		30-day postoperative
Chest pain rate according to CTCAE v4.0		30-day postoperative
Dyspnea according to Medical Research Council (MRC) chronic dyspnea scale (5-point)		30-day postoperative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Malignant effusion recurrence-free - percentage of patients without recurrent pleural effusion at 30 days		30 days after treatment
Dyspnea reduction according to CTCAE v4.0	CTCAE v4.0	30 days after treatment
Tumor response	Evaluation Criteria in Solid Tumors (RECIST) version 1.1.	according to local standard
Overall survival (OS)		every 3 months up to 3 years
Overall response rate (ORR) based on investigator assessment according to Response	Evaluation Criteria in Solid Tumors (RECIST) version 1.1	according to local standard
Progression-free survival (PFS)	Evaluation Criteria in Solid Tumors (RECIST) version 1.1	according to local standard
Duration of Response (DOR)	Evaluation Criteria in Solid Tumors (RECIST) version 1.1	according to local standard

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire Vaudois
• Investigators: Study Director: Hans-Beat Ris, MD, Prof., CHUV

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (ACTUAL): August 28, 2018
• Study Completion (ACTUAL): August 28, 2018

Study Registration Dates

• First Submitted: January 25, 2016
• First Submitted That Met QC Criteria: March 3, 2016
• First Posted (ESTIMATE): March 9, 2016

Study Record Updates

• Last Update Posted (ACTUAL): March 20, 2019
• Last Update Submitted That Met QC Criteria: March 18, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Neoplasms by Site; Pleural Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Pleural Neoplasms; Pleural Effusion, Malignant; Pleural Effusion; Antineoplastic Agents; Photosensitizing Agents; Dermatologic Agents; Verteporfin; Cisplatin
• Other Study ID Numbers: CHUV-DO-PDT-2015