OPC5: Pressurized IntraThoracic Aerosol Chemotherapy (PITAC) in Patients With Malignant Pleural Effusion.

Quality of Life Clinical Trial

Official title:

Implementation and Evaluation of Pressurized Intrathoracic Aerosol Chemotherapy (PITAC) for the Treatment of Patients With Malignant Pleural Effusion. A Danish Phase I Study (OPC5 Study)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06421610
• Other study ID #: PITAC-OPC5
• Status: Recruiting
• Phase: Phase 1
• Start date: September 15, 2023
• Est. completion date: December 31, 2024

Study information

• Verified date: May 2024
• Source: Odense University Hospital
• Contact: Pernille Schjødt Hansen, Student
• Phone: +45 65411857
• Email: pernille.schjodt.hansen[@]rsyd.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will monitor and evaluate patient and personnel safety and toxicity during the implementation and evaluation of Pressurized IntraThoracic Aerosol Chemotherapy (PITAC) directed treatment. Furthermore, this study will focus on Quality of Life questionnaires, LENT score, and evaluate pain and breathlessness using af visual analogue scales (VAS).

Description:

This is a safety and feasibility study of repeated (minimum two procedures) PITAC directed treatments, and the primary outcome is the number of patients with medical adverse events (AEs) according to the Common Terminology Criteria for Adverse Events (CTCAE) and/or surgical complications according to the Clavien-Dindo classification. This study will include consecutive MPE patients until 20 patients have completed at least two PITAC´s. The PITAC directed treatment will be performed in 4 week intervals. Bedside ultrasound, VAS-pain and VAS-breathlessness, and Quality of Life questionnaires will be performed at baseline, one month follow-up and three months follow-up. Patients with MPE who are eligible for surgery are identified during the multidisciplinary tumor (MDT) conference at the Department of Surgery, Odense University Hospital (OUH), and included based on predefined in- and exclusion criteria. Patients with MPE from non-colorectal or -appendix cancer will be treated with a combination of cisplatin and doxorubicin. Patients with MPE from colorectal or appendix cancer will be treated with oxaliplatin. In brief, The PITAC procedure is the application of aerosolized chemotherapy into the pleural cavity using thoracoscopy. PITAC is performed in the prone or lateral position. A double lumen endotracheal tube is used to allow exclusion of the ipsilateral lung, but this is not (always) necessary with the patient in the prone position. The first trocar is placed guided by ultrasound, and after safe positioning a second trocar can be inserted guided by video thoracoscopy. The chemotherapy is applied to the pleural cavity through a nebulizer inserted through one of the trocars and linked to a high-pressure injector. After five minutes the chemotherapy has been delivered to the pleural cavity, and after an additional 30 minutes of simple diffusion, the intrathoracic air saturated with chemotherapy is evacuated through a series of filters. The patients are monitored for a minimum of one day and will after each PITAC directed treatment be screened for adverse events.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Symptomatic MPE visible with bedside ultrasound
• Histologically or cytologically verified malignancy
• Status CT-scan not older than four weeks
• MPE requiring at least one drainage procedure
• Drained = 14 days before the first PITAC directed treatment
• Bidirectional systemic chemotherapy or immunotherapy = 14 days before the first PITAC directed treatment or no simultaneous systemic chemotherapy or immunotherapy
• ECOG Performance status 0-2
• Life expectancy = 3 months
• Age = 18 years
• Danish-speaking and reading patients
• Written informed consent according to the local Ethics Committee requirements

Exclusion Criteria:

• A history of allergic reaction to cisplatin or other platinum containing compounds or doxorubicin
• Renal impairment, defined as GFR < 40 ml/min (Cockcroft-Gault Equation)
• Myocardial insufficiency, defined as NYHA class > 2
• Impaired liver function defined as bilirubin =1.5
• Fertility, pregnancy and lactation: Female subjects will be considered of

non-reproductive potential if they are either a, b or c:

1. postmenopausal (defined as at least 12 months with no menses without an alternative medical cause; in women < 45 years of age a high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. In the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.

2. have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy or bilateral tubal ligation/occlusion, at least 6 weeks prior to screening.

3. have a congenital or acquired condition that prevents childbearing. Previous intrathoracic chemotherapy, intrathoracic antibody treatment or chemical pleurodesis

• Any other condition or therapy, which in the investigator´s opinion may pose a risk to the patient or interfere with the study objects

Related Conditions & MeSH terms

• Carcinoma
• Chemotherapeutic Toxicity
• Chemotherapy Effect
• Malignant Pleural Effusion
• Pleural Carcinomatosis
• Pleural Effusion
• Pleural Effusion, Malignant
• Pleural Neoplasms
• Quality of Life

Intervention

Drug:
• PITAC
Cisplatin, oxaliplatin and doxorubicin are standard, commercially available intravenous cytostatic drugs in oncologic treatment with alkylating and topoisomerase inhibitor effect, respectively. Based on the available data and experience from 11 PITAC procedures at OPC, PITAC with cisplatin, oxaliplatin and doxorubicin for intrapleural administration is expected to be well tolerated with a minimal of nausea, subcutaneous emphysema and transient chest pains.

Locations

Country	Name	City	State
Denmark	Odense PIPAC Center, Department of Surgery, Odense University Hospital	Odense

Sponsors (1)

Lead Sponsor	Collaborator
Odense University Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Medical adverse events	Number of patients with medical adverse events (AEs) according to the Common Terminology Criteria for Adverse Events (CTCAE) version 6.0 defined as CTCAE = 4 within 30 days after the procedure.	30 days from PITAC directed treatment
Primary	Surgical complications	Number of patients with surgical complications according to the Clavien-Dindo classification defined as Clavien-Dindo = 3b within 30 days after the procedure.	30 days from PITAC directed treatment
Secondary	Number of patients completing three PITAC treatments	To evaluate the number of patients completing three PITAC treatments	12 months
Secondary	Extent of visible pleural metastasis	To macroscopically evaluate the extent of visible pleural metastasis (PLM) during PITAC directed therapy via the new PLM-score based on size of lesions (LS).; LS 0 No tumor seen LS1 Tumor up to 0.5 cm LS2 Tumor up to 5.0 cm LS3 Tumor > 5.0 cm or confluence	12 months
Secondary	Pathology on pleural metastasis biopsies	To evaluate Pleural Regression Grade Score (Ple-RGS) in biopsies from visible pleural metastasis Ple-RGS is a modification of the Peritoneal Regression Grading score (PRGS). Ple-RGS 1: Complete histological response Ple-RGS 2: Regressive changes are predominant over cancer cells (major response) Ple-RGS 3: Cancer cells are predominant over regressive changes (minor response) Ple-RGS 4: No response	12 months
Secondary	Cytology on malignant pleural effusion fluid	To evaluate cytology on MPE during PITAC directed therapy. The cells will be graded according to a five-tiered score: malignant cells, suspicious cells, atypical cells, no malignant cells and other	12 months
Secondary	LENT score	To evaluate the LENT score after each PITAC directed therapy. Low risk: 0-1 Moderate risk: 2-4 High risk: 5-7	12 months
Secondary	Length of Stay (LOS)	Quantify the length of stay (LOS) (surgery = day 0)	12 months
Secondary	Personnel safety (environmental)	Assess personnel safety by measuring of platinum traces in the operating room.	12 months
Secondary	Personnel safety (biological)	Assess personnel safety by measuring of platinum traces in blood samples from surgeons and/or OR nurses.	12 months
Secondary	Lung function evaluation by SAT	To evaluate lung function by saturation (SAT) before PITAC directed treatment (day 0) and at discharge (day 1), day 30 and 3 months after the last PITAC directed treatment	12 months
Secondary	Breathlessness	To evaluate breathlessness using visual analogue scales (VAS-breath) before PITAC directed treatment (day 0) and at discharge (day 1), day 30, and 3 months after the last PITAC directed treatment	12 months
Secondary	Pain assessment	To evaluate pain using visual analogue scales (VAS-pain) before PITAC directed treatment (day 0) and at discharge (day 1), day 30, and 3 months after the last PITAC directed treatment	12 months
Secondary	Quality of Life questionnaires	To evaluate the quality of life with EORTC-QLQ-C30 at baseline, day 30 and 3 months after the last PITAC directed treatment	12 months
Secondary	Change in MPE volume	To calculate the change in volume of drained MPE from 2 months before the first PITAC treatment to three months after the last PITAC treatment	12 months
Secondary	Long term complications	To assess long-term complications 3 months after the third PITAC directed treatment	12 months
Secondary	Survival	Median overall survival	12 months
Secondary	Lung function evaluation by FEV1	To evaluate lung function by Forced Expired Volume in the first second (FEV1) before PITAC directed treatment (day 0) and at discharge (day 1), day 30 and 3 months after the last PITAC directed treatment	12 months