Back to resultsPhoto-induction as a Means to Improve Cisplatin Delivery to Pleural Malignancies (PDT-lipo)
Primary Purpose
Pleural Effusion, Malignant
Status
Terminated
Phase
Phase 1
Locations
Switzerland
Study Type
Interventional
Intervention
Cisplatin, liposomal
Verteporfin
Device for Intrapleural Visudyne-mediated Low-Dose Photodynamic Therapy with integrated in situ light dosimetry
Sponsored by
About this trial
This is an interventional treatment trial for Pleural Effusion, Malignant
Eligibility Criteria
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
Sites / Locations
- Oncology Department, Centre Hospitalier Universitaire Vaudois (CHUV)
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Lipoplatin/Visudyne-mediated photodynamic therapy
Arm Description
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.
Outcomes
Primary Outcome Measures
Safety of the treatment as assessed by 30-day postoperative mortality
survival status at 30 days
Tolerability of the treatment as assessed by 30-day postoperative mortality
survival status at 30 days
Feasibility
survival status at 30 days
Acute respiratory failure rate
Dyspnea according to CTCAE v4.0
Chest pain rate according to CTCAE v4.0
Dyspnea according to Medical Research Council (MRC) chronic dyspnea scale (5-point)
Secondary Outcome Measures
Malignant effusion recurrence-free - percentage of patients without recurrent pleural effusion at 30 days
Dyspnea reduction according to CTCAE v4.0
CTCAE v4.0
Tumor response
Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Overall survival (OS)
Overall response rate (ORR) based on investigator assessment according to Response
Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Progression-free survival (PFS)
Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Duration of Response (DOR)
Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Full Information
NCT ID
NCT02702700
First Posted
January 25, 2016
Last Updated
March 18, 2019
Sponsor
Centre Hospitalier Universitaire Vaudois
1. Study Identification
Unique Protocol Identification Number
NCT02702700
Brief Title
Photo-induction as a Means to Improve Cisplatin Delivery to Pleural Malignancies
Acronym
PDT-lipo
Official Title
Photo-induction as a Means to Improve Cisplatin Delivery to Pleural Malignancies: a Clinical Phase I Trial
Study Type
Interventional
2. Study Status
Record Verification Date
March 2019
Overall Recruitment Status
Terminated
Why Stopped
Drug supply issue
Study Start Date
January 2016 (undefined)
Primary Completion Date
August 28, 2018 (Actual)
Study Completion Date
August 28, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Centre Hospitalier Universitaire Vaudois
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pleural Effusion, Malignant
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
1 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Lipoplatin/Visudyne-mediated photodynamic therapy
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Cisplatin, liposomal
Other Intervention Name(s)
Lipoplatin™
Intervention Description
Lipoplatin IV 200 mg/m2
Intervention Type
Drug
Intervention Name(s)
Verteporfin
Other Intervention Name(s)
Visudyne®
Intervention Description
Visudyne® IV 3 mg/m2
Intervention Type
Device
Intervention Name(s)
Device for Intrapleural Visudyne-mediated Low-Dose Photodynamic Therapy with integrated in situ light dosimetry
Intervention Description
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.
Primary Outcome Measure Information:
Title
Safety of the treatment as assessed by 30-day postoperative mortality
Description
survival status at 30 days
Time Frame
30 days
Title
Tolerability of the treatment as assessed by 30-day postoperative mortality
Description
survival status at 30 days
Time Frame
30 days
Title
Feasibility
Description
survival status at 30 days
Time Frame
30 days
Title
Acute respiratory failure rate
Time Frame
30-day postoperative
Title
Dyspnea according to CTCAE v4.0
Time Frame
30-day postoperative
Title
Chest pain rate according to CTCAE v4.0
Time Frame
30-day postoperative
Title
Dyspnea according to Medical Research Council (MRC) chronic dyspnea scale (5-point)
Time Frame
30-day postoperative
Secondary Outcome Measure Information:
Title
Malignant effusion recurrence-free - percentage of patients without recurrent pleural effusion at 30 days
Time Frame
30 days after treatment
Title
Dyspnea reduction according to CTCAE v4.0
Description
CTCAE v4.0
Time Frame
30 days after treatment
Title
Tumor response
Description
Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Time Frame
according to local standard
Title
Overall survival (OS)
Time Frame
every 3 months up to 3 years
Title
Overall response rate (ORR) based on investigator assessment according to Response
Description
Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Time Frame
according to local standard
Title
Progression-free survival (PFS)
Description
Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Time Frame
according to local standard
Title
Duration of Response (DOR)
Description
Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Time Frame
according to local standard
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hans-Beat Ris, MD, Prof.
Organizational Affiliation
CHUV
Official's Role
Study Director
Facility Information:
Facility Name
Oncology Department, Centre Hospitalier Universitaire Vaudois (CHUV)
City
Lausanne
State/Province
Vaud (VD)
ZIP/Postal Code
1011
Country
Switzerland
12. IPD Sharing Statement
Learn more about this trial
Photo-induction as a Means to Improve Cisplatin Delivery to Pleural Malignancies
We'll reach out to this number within 24 hrs