Pleural Effusion, Malignant
Conditions
Brief summary
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.
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).
Interventions
DRUGCisplatin, liposomal
Lipoplatin IV 200 mg/m2
DRUGVerteporfin
Visudyne® IV 3 mg/m2
DEVICEDevice 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.
Sponsors
Centre Hospitalier Universitaire Vaudois
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dyspnea according to Medical Research Council (MRC) chronic dyspnea scale (5-point) | 30-day postoperative | — |
| Safety of the treatment as assessed by 30-day postoperative mortality | 30 days | survival status at 30 days |
| Tolerability of the treatment as assessed by 30-day postoperative mortality | 30 days | survival status at 30 days |
| Feasibility | 30 days | survival status at 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 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 30 days after treatment | CTCAE v4.0 |
| Tumor response | according to local standard | Evaluation Criteria in Solid Tumors (RECIST) version 1.1. |
| Overall survival (OS) | every 3 months up to 3 years | — |
| Overall response rate (ORR) based on investigator assessment according to Response | according to local standard | Evaluation Criteria in Solid Tumors (RECIST) version 1.1 |
| Progression-free survival (PFS) | according to local standard | Evaluation Criteria in Solid Tumors (RECIST) version 1.1 |
| Duration of Response (DOR) | according to local standard | Evaluation Criteria in Solid Tumors (RECIST) version 1.1 |
Countries
Switzerland
Outcome results
None listed