Mesothelioma, MalignantPhase 1PITHACNCT06281860
Treatment Pleural Carcinosis of Pressurized IntraThoracic Hyperthermic Aerosol Cisplatin Administration
A Phase 1 study testing Cisplatine Teva® in people with Mesothelioma, Malignant and Carcinoma, Non-Small-Cell Lung, run by Dr Jean Yannis PERENTES at 1 site in Switzerland.
Trial summary
Within the context of pleural carcinosis, the present study is a dose escalation with determination of the maximum tolerated doses (MTD) of pressurized cisplatin administration associated to moderate hyperthermia in the pleura. This will be followed by an expansion phase at the recommended dose (RD). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mesothelioma, Malignant, Carcinoma, Non-Small-Cell Lung, Carcinoma Breast Stage IV
- What is being tested?
- Cisplatine Teva®
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 1 siteSwitzerland
- Study dates
- 24 Nov 2023to 1 Feb 2026
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- At least 18 years of age
- Body weight at least 30 kg
- Eastern cooperative oncology group performance status score of 0-2 at enrolment
- Patient with pleural carcinosis that qualify for a surgical intervention for pleurodesis or placement of an indwelling permanent catheter.
- Life expectancy of at least 3 months
- Pathology-confirmed pleural carcinosis with malignant pleural effusion (either histological confirmation is already available based on a previous tru-cut pleural biopsy or previous pleural fluid cytology is positive for malignant cells or high suspicion of pleural carcinosis based on computed tomography imaging which must be confirmed by fresh frozen section analyses of tissue harvested during pithac operative procedure)
Show all 13Show fewer
- Non-small cell lung cancer, breast cancer, lymphoma, ovarian cancer, oesophageal cancer, gastric cancer, and malignant tumour of the serous membranes (mesothelioma) confirmed by pathology either as part of a diagnostic workup of suspected pleural carcinosis OR available from other previous examinations patients undergoing a planned videothoracoscopy to perform pleurodesis or a placement of a tunnelled catheter
- Adequate liver, kidney, and bone marrow functions as assessed by laboratory tests (serum total bilirubin <1.5 mg/dl, aspartate transaminase and alanine transaminase less than 2.5 times the upper limit of the normal range, creatinine clearance ≥60 ml/min, absolute neutrophil count ≥1,500/μl, haemoglobin ≥90 g/L, platelets ≥100,000/μl)
- I) Patients with past/resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible, if HBV DNA test is negative. Ii) HBV DNA must be obtained in patients with positive hepatitis B core antibody prior start of study treatment.
- Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA
- Adequate cardiac functions as assessed by echocardiography
- Adequate birth control measures
- Signed informed consent
Who cannot join
- Patients with active or chronic hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test at pre-screening)
- Patients with active hepatitis C
- Any known formal contra-indication for video-assisted thoracoscopy (VATS) according to pulmonary and cardiac preliminary investigations.
- Systemic cytotoxic anticancer treatment within 10 days before and after enrolment except for inhibitors of vascular endothelial growth factor for which this period should be decided according to the used drug (for bevacizumab the period involves 4 weeks before and after enrolment, for lenvatinib 1 week before and 2 weeks after, and for sorafenib 1 week before and after), no limitations applied for immune checkpoint inhibitors
- Major surgery within 28 days prior to enrolment
- Any unresolved toxicity from previous anticancer therapy of grade ≥2 according to the CTCAE except for alopecia, vitiligo, and laboratory values considered as adequate in the inclusion criteria and any irreversible toxicity that is expected to have impact on the study results or be a contraindication for the planned surgical intervention or be worsened by the investigational procedure
Show all 23Show fewer
- Long lasting exposure to corticosteroids
- Known allergy to platinum compounds
- Non-small cell lung cancer with egfr or alk mutations unless refractory to tyrosine kinase inhibitor (thus off treatment)
- Uncontrolled intercurrent illness
- Clinically relevant hearing loss or tinnitus
- Clinically relevant neuropathy
- Life-threatening conditions (uncontrolled systemic infection etc.)
- Previous administration (by any route) of a total cumulative dose of more than 500 mg/m2 of cisplatin
- Secondary resistance to platinum compounds defined as tumour progression during platinum treatment or within 6 months after its cessation
- pregnancy
- judgement of the investigator that the patient is unlikely to comply with the study requirements
- current enrolment in another prospective clinical trial
- Incapacity of judgement
- Patients in emergency situation
- Myelossupression
- Yellow fever vaccine
- Concurrent prophylactic use of phenytoin
Trial locations and contacts
1 site in 1 country.
Switzerland1 site, 1 recruiting
- Recruiting
Centre Hospitalier Universitaire Vaudois
Lausanne
Jean-Yannis PERENTES
Jean Yannis PERENTES
About this study
Official title: Phase I Clinical Trial Testing the Dose Escalation and Expansion of Pressurized IntraThoracic Hyperthermic Aerosol Cisplatin Administration for the Management of Pleural Carcinosis
Within the context of pleural carcinosis, the present study is a dose escalation with determination of the maximum tolerated doses (MTD) of pressurized cisplatin administration associated to moderate hyperthermia in the pleura. This will be followed by an expansion phase at the recommended dose (RD).
Read the detailed description
Adverse events: the evaluation of the safety of cisplatin administered by PITHAC is the primary endpoint of both parts of the study Cisplatin administration will be performed on D0. Postoperative pain management according to the Enhanced Recovery After Surgery program following the surgical procedure.
Dyspnoea score will be scored at screening, and every day until D10 and checked one last time at D30 using the CR-10 scale.
Chest X-ray will be performed at screening, D0, 24h post intervention, D10 and D30.
Monitoring of adverse events (AEs), serious and non-serious, will be conducted throughout the study from the surgery.
Blood samples for cisplatin pharmacokinetics PK will be performed on D0 pre-intervention, 12h post intervention, 24h and 48h post intervention.
Translational blood tests for immune profiling will be performed on D0 pre-intervention, D10 and D30. Translational blood tests on inflammatory cytokine assessment will be performed on D0 pre-intervention, 12h post intervention, 24h, 48h and on D10 and D30. Tissue biopsy for free cisplatin PK and Pleural biopsy for tissue immune infiltration will be performed on D0 before and after treatment administration.
Malignant pleural effusion (MPE) assessment: Immune environment and neoantigen landscape will be collected before the PITHAC procedure and via the indwelling pleural catheter (D0, at hospital discharge and D10).
STATISTICAL METHODS:
PART A: Dose escalation and MTD determination: The sample size is set to determine the MTD by using the 3+3 design. Cohorts of 3-6 patients will be recruited sequentially at each of the cisplatin doses. The total number of patients is expected to be 12 with a maximum of 24, depending on the level of MTD. If there are patients who are not evaluable for the objectives in the study, additional patients will be enrolled. Patients not evaluable will be replaced but not withdrawal from the study.
Primary Analysis: dose limiting toxicities; To determine the maximum tolerated dose (MTD) of cisplatin administered with PITHAC, the primary study outcome is the occurrence of Dose Limiting Toxicities (DLT). The number and proportion of patients with DLTs will be presented overall and by dose and will be plotted vs dose. The MTD will be graphically displayed. Secondary Analyses: safety profile of cisplatin administered with PITHAC: The safety analysis will be performed on the safety population. -Treatment emergent AE frequencies will be summarised by system organ class and preferred term (MedDRA) overall and by dose. AEs will also be tabulated by system organ class and preferred term including maximum severity grade according to the NCI-CTCAE criteria version 5 and relationship to treatment. Incidence of treatment discontinuations due to AEs and SAEs will be summarised overall and by dose. -Safety Lab parameters and vital signs at pre-treatment and post-treatment and corresponding changes from pre-treatment will be presented by dose as descriptive statistics. Efficacy analysis will be performed on efficacy population. Dyspnoea will be scored from screening to D30. Dyspnoea score will be presented at pre- and post-treatment and change from pre- to post-treatment will be presented as descriptive statistics by dose. The pleural infusion index will be determined by comparing chest X-rays before treatment (D0) and post-treatment at D1, D10 and 30 days and pleurodesis or indwelling catheter placement. The index will be presented at pre- and post-treatment and change from pre- to post-treatment will be presented as descriptive statistics by dose. Exploratory endpoints: exploratory analyses will be performed by tissue immunostaining and image analysis will be carried out. The concentration of cisplatin in tumor tissue at the beginning and end of mild hyperthermia PITHAC will be evaluated by Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS) that will allow visualization of cisplatin distribution and penetration in tumor biopsies. The correlation between cisplatin concentration and penetration into tumor tissue and clinical response will be explored. Immune infiltration in tumor tissues will be assessed by immunostainings and image analysis will be performed. Immune cells proportions in peripheral blood before and after PITHAC at D0, 10 and 30 will be explored using DURAClone Panels for flow cytometry.
PART B: Expansion: Determination of Sample Size: the sample in the expansion phase is not based on a formal hypothesis. To evaluate the safety of cisplatin administered by PITHAC at the RD and undertake an initial evaluation of efficacy, a total of 15 patients will be enrolled in this exploratory part of the study. Statistical criteria of termination of trial: there are no statistical criteria of termination of the trial in this part of the study.
Primary Analysis: dose limiting toxicities; To determine the maximum tolerated dose (MTD) of cisplatin administered with PITHAC, the primary study outcome is the occurrence of Dose Limiting Toxicities (DLT). The number and proportion of patients with DLTs will be presented overall and by dose and will be plotted vs dose. The MTD will be graphically displayed. Secondary Analyses: safety profile of cisplatin administered with PITHAC: The safety analysis will be performed on the safety population. -Treatment emergent AE frequencies will be summarised by system organ class and preferred term (MedDRA) overall and by dose. AEs will also be tabulated by system organ class and preferred term including maximum severity grade according to the NCI-CTCAE criteria version 5 and relationship to treatment. Incidence of treatment discontinuations due to AEs and SAEs will be summarised overall and by dose. -Safety Lab parameters and vital signs at pre-treatment and post-treatment and corresponding changes from pre-treatment will be presented by dose as descriptive statistics. Efficacy analysis will be performed on efficacy population. Dyspnoea will be scored from screening to D30. Dyspnoea score will be presented at pre- and post-treatment and change from pre- to post-treatment will be presented as descriptive statistics by dose. The pleural infusion index will be determined by comparing chest X-rays before treatment (D0) and post-treatment at D1, D10 and 30 days and pleurodesis or indwelling catheter placement. The index will be presented at pre- and post-treatment and change from pre- to post-treatment will be presented as descriptive statistics by dose. Exploratory endpoints: exploratory analyses will be performed by tissue immunostaining and image analysis will be carried out. The concentration of cisplatin in tumor tissue at the beginning and end of mild hyperthermia PITHAC will be evaluated by Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS) that will allow visualization of cisplatin distribution and penetration in tumor biopsies. The correlation between cisplatin concentration and penetration into tumor tissue and clinical response will be explored. Immune infiltration in tumor tissues will be assessed by immunostainings and image analysis will be performed. Immune cells proportions in peripheral blood before and after PITHAC at D0, 10 and 30 will be explored using DURAClone Panels for flow cytometry.
QUALITY ASSURANCE AND CONTROL: all data collected will be coded and recorded on the RedCap search software. The conformity of eCRF with protocol specifications is checked and validated by the SI and/or qualified individuals, according to ICH GCP. Case Report Forms (eCRF): electronic data entry will be performed via a web-based application (REDCap). Security passwords will be provided to each properly trained investigator. An eCRF for data collection will be developed in Redcap. The REDCap database will record the data obtained with the coding number specific to each patient: this code will consist of PITHAC-01, PITHAC-02 etc…. A specific subject identification log will be compiled to record the identifying information of enrolled participants, providing the link to individual attributed codes. This document (word file) will be kept separately, it will be password protected and saved in a secure directory on a CHUV server. At the end of the project, the subject identification log will be kept by the principal investigator. Best practices will be adopted to ensure that data are complete, reliable, and processed correctly, thus providing high-quality data, keeping the number of errors and missing data as low as possible, and gathering a maximum amount of accurate data for analysis. The data collected through RedCap® will be automatically checked by the implementation of data validation rules (e.g., data-type, maximum/minimum range, missing data checks, and other logical tests) and automatic alerts. Specification of source documents: study monitors will perform ongoing source data verification to confirm that critical protocol data (i.e., source data) entered into the eCRFs by authorized site personnel are accurate, complete, and verifiable from source documents. Source documents (paper or electronic) are those in which patient data are recorded and documented for the first time. They include, but are not limited to, hospital records, clinical and office charts, laboratory notes, memoranda, evaluation checklists, pharmacy dispensing records, recorded data from automated instruments, copies of transcriptions that are certified after verification as being accurate and complete, X-rays, patient files, and records kept at pharmacies, laboratories, and medico-technical departments involved in the clinical trial. The Investigator must keep a subject file (medical file, original medical records) electronically (SOARIAN/ARCHIMEDE) for every subject included in the trial. All documents containing source data must be filed in the electronic patient file. Electronic subject files (SOARIAN/ARCHIMEDE) will be accessible to the Monitor to perform source data verification. Record keeping / archiving: the SI will retain copies of the patient trial records (CRFs, patient informed consent statement, drug inventory logs and all other information collected during the trial) and documentation until at least 10 years after the termination of the trial.It must be available for review by the Monitor and must be ready for Sponsor audit as well as for inspection by Competent Authorities during and after the trial and must be safely archived for at least 10 years (or per local requirements or as otherwise notified by the Sponsor) after the end of the trial. The documents to be thus archived include the Subject Identification List and the signed subject ICFs.
Safety Monitoring (Dose Escalation Part): a Trial Safety Board (TSB) will be constituted for the part A of the trial, being responsible for maintaining the scientific integrity of the trial and safety of patients. This Board will review the DLTs of each cohort and decide whether to escalate or not to the next dose level (next cohort). Details on the dose escalation design, rules, and the role of the TSB are provided in the DEP. The TSB will give the green light to start part B after recommended dose confirmation, based on safety and efficacy data of all patients enrolled in part A. For Part B, the responsibility for the safety of the individual patient lies with the investigator and the SI. Clinical Trial Monitoring: clinical monitoring activities have the ultimate purpose to guarantee that the rights and well-being of human subjects are protected, that the reported study data are accurate, complete and verifiable from source documents, and that the conduct of the study complies with the latest approved version of the study protocol, with ICH-GCP guidelines and applicable regulations .
- Conditions
- Mesothelioma, Malignant, Carcinoma, Non-Small-Cell Lung, Carcinoma Breast Stage IV, Ovarian Cancer, Esophageal Cancer, Gastric Cancer
- Being tested
- Cisplatine Teva®
- Keywords
- Pressurized intrathoracic hyperthermic aerosol chemotherapy
- Medical subject headings
- Mesothelioma, Malignant, Carcinoma, Non-Small-Cell Lung, Breast Neoplasms, Ovarian Neoplasms, Esophageal Neoplasms, Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cisplatine Teva®Drug
Also called Procedure/Surgery
PITHAC: Cisplatin (Cisplatine Teva®) at a dose between 7.5 and 70 mg/m2 of body surface at a temperature of 39±1°C
| Study group | Role | What they receive |
|---|---|---|
| Cohorte 1 _ 7.5 mg/m2 | Experimental | cohorte 1: 7.5 mg/m2 of cisplatin (once) Receives: Drug: Cisplatine Teva® |
| Cohorte 2 _ 12.5 mg/m2 | Experimental | cohorte 2: 12.5 mg/m2 of cisplatin (once) Receives: Drug: Cisplatine Teva® |
| cohorte 3: 35 mg/m2 of cisplatin | Experimental | cohorte 3: 35 mg/m2 of cisplatin (once) Receives: Drug: Cisplatine Teva® |
| cohorte 4: 70 mg/m2 of cisplatin | Experimental | cohorte 4: 70 mg/m2 of cisplatin (once) Receives: Drug: Cisplatine Teva® |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Escalation and Maximum Tolerated Dose determination (Part A):
In order to determine the maximum tolerated dose (MTD) of cisplatin administered by PITHAC, the primary study outcome will be the occurrence of Dose Limiting Toxicities (DLT).
Measured: 18 months approximately
Expansion phase (Part B):
Safety profile of cisplatin administered by PITHAC will be assessed by the incidence of Adverse Events and Serious Adverse Events according to NCI-CTCAE criteria (v5). Incidence and severity of intraoperative and post-operative complications will be measured using the Clavien-Dindo classification up to 30 days after the intervention.
Safety profile of cisplatin administered by PITHAC will be assessed by the incidence of Adverse Events and Serious Adverse Events according to NCI-CTCAE criteria (v5). Incidence and severity of intraoperative and post-operative complications will be measured using the Clavien-Dindo classification up to 30 days after the intervention.
Measured: between 10 and 12 months
Secondary outcomes (2)
Dose Escalation and MTD determination (Part A):
Safety profile of cisplatin administered with moderate hyperthermic PITHAC will be assessed by the incidence of Adverse Events and Serious Adverse Events according to NCI-CTCAE criteria (v5).
Dyspnoea will be scored every day until Day 10 and re-evaluated at Day 30 after the procedure
The pleural effusion index will be determined by comparing chest X-rays before, 24 hours (Day 0), at Day 10 and at Day 30 after PITHAC and pleurodesis or indwelling catheter placement
Measured: 18 months
Expansion phase (Part B):
Dyspnoea will be scored every day until Day 10 and re-evaluated at Day 30 after the procedure.
The pleural effusion index will be determined by comparing chest X-rays before PITHAC procedure, 24 hours after, at Day 10 and Day 30 after PITHAC and pleurodesis or indwelling catheter placement.
Measured: 10 /12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2024
- Study start24 Nov 2023
- Primary completion1 Dec 2025 (estimated)
- Study completion1 Feb 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Mesothelioma, MalignantStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- Open-label, non-randomised monocentric Phase I clinical trial study with cisplatin dose escalation administered by PITHAC.
- Masking
- None (open label)
- Enrolment
- 39 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Dr Jean Yannis PERENTES
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Dr Jean Yannis PERENTES, Centre Hospitalier Universitaire Vaudois
- Investigators
- Jean-Yannis Perentes, Principal investigator, Centre Hospitalier Universitaire Vaudois
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06281860
- Sponsor's protocol ID
- PITHAC
- Other IDs
- 2023-00099, 2023
- Acronym
- PITHAC
- Status last verified
- Feb 2024
- First submitted
- 16 Sep 2023
- Last updated
- 28 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Chriqui LE, Abdelnour-Berchtold E, Zanfrini E, Devesa-Perez S, Gonzalez M, Krueger T, Ellefsen K, Destaillats A, Bonnet D, Hubner M, Bouchaab H, Bassani-Sternberg M, Peters S, Cavin S, Perentes JY. Phase I clinical trial testing the dose escalation and expansion of Pressurized IntraThoracic Hyperthermic Aerosol Cisplatin administration (PITHAC) for the management of pleural carcinosis. Cancer Treat Res Commun. 2024;42:100858. doi: 10.1016/j.ctarc.2024.100858. Epub 2024 Dec 17.
PubMed 39708537
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Clinical Trial Testing the Dose Escalation and Expansion of Pressurized IntraThoracic Hyperthermic Aerosol Cisplatin Administration for the Management of Pleural Carcinosis
- ClinicalTrials.gov ID
- NCT06281860
- Acronym / sponsor ID
- PITHAC / PITHAC
- Conditions
- Mesothelioma, Malignant, Carcinoma, Non-Small-Cell Lung, Carcinoma Breast Stage IV, Ovarian Cancer, Esophageal Cancer, Gastric Cancer
- Keywords
- Pressurized intrathoracic hyperthermic aerosol chemotherapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 39 participants (estimated)
- Lead sponsor
- Dr Jean Yannis PERENTESUniversity, hospital or other
- Study start
- 24 Nov 2023 (actual)
- Primary completion
- 1 Dec 2025 (estimated)
- Study completion
- 1 Feb 2026 (estimated)
- First posted
- 28 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Within the context of pleural carcinosis, the present study is a dose escalation with determination of the maximum tolerated doses (MTD) of pressurized cisplatin administration associated to moderate hyperthermia in the pleura. This will be followed by an expansion phase at the recommended dose (RD).
Detailed description
Adverse events: the evaluation of the safety of cisplatin administered by PITHAC is the primary endpoint of both parts of the study Cisplatin administration will be performed on D0. Postoperative pain management according to the Enhanced Recovery After Surgery program following the surgical procedure.
Dyspnoea score will be scored at screening, and every day until D10 and checked one last time at D30 using the CR-10 scale.
Chest X-ray will be performed at screening, D0, 24h post intervention, D10 and D30.
Monitoring of adverse events (AEs), serious and non-serious, will be conducted throughout the study from the surgery.
Blood samples for cisplatin pharmacokinetics PK will be performed on D0 pre-intervention, 12h post intervention, 24h and 48h post intervention.
Translational blood tests for immune profiling will be performed on D0 pre-intervention, D10 and D30. Translational blood tests on inflammatory cytokine assessment will be performed on D0 pre-intervention, 12h post intervention, 24h, 48h and on D10 and D30. Tissue biopsy for free cisplatin PK and Pleural biopsy for tissue immune infiltration will be performed on D0 before and after treatment administration.
Malignant pleural effusion (MPE) assessment: Immune environment and neoantigen landscape will be collected before the PITHAC procedure and via the indwelling pleural catheter (D0, at hospital discharge and D10).
STATISTICAL METHODS:
PART A: Dose escalation and MTD determination: The sample size is set to determine the MTD by using the 3+3 design. Cohorts of 3-6 patients will be recruited sequentially at each of the cisplatin doses. The total number of patients is expected to be 12 with a maximum of 24, depending on the level of MTD. If there are patients who are not evaluable for the objectives in the study, additional patients will be enrolled. Patients not evaluable will be replaced but not withdrawal from the study.
Primary Analysis: dose limiting toxicities; To determine the maximum tolerated dose (MTD) of cisplatin administered with PITHAC, the primary study outcome is the occurrence of Dose Limiting Toxicities (DLT). The number and proportion of patients with DLTs will be presented overall and by dose and will be plotted vs dose. The MTD will be graphically displayed. Secondary Analyses: safety profile of cisplatin administered with PITHAC: The safety analysis will be performed on the safety population. -Treatment emergent AE frequencies will be summarised by system organ class and preferred term (MedDRA) overall and by dose. AEs will also be tabulated by system organ class and preferred term including maximum severity grade according to the NCI-CTCAE criteria version 5 and relationship to treatment. Incidence of treatment discontinuations due to AEs and SAEs will be summarised overall and by dose. -Safety Lab parameters and vital signs at pre-treatment and post-treatment and corresponding changes from pre-treatment will be presented by dose as descriptive statistics. Efficacy analysis will be performed on efficacy population. Dyspnoea will be scored from screening to D30. Dyspnoea score will be presented at pre- and post-treatment and change from pre- to post-treatment will be presented as descriptive statistics by dose. The pleural infusion index will be determined by comparing chest X-rays before treatment (D0) and post-treatment at D1, D10 and 30 days and pleurodesis or indwelling catheter placement. The index will be presented at pre- and post-treatment and change from pre- to post-treatment will be presented as descriptive statistics by dose. Exploratory endpoints: exploratory analyses will be performed by tissue immunostaining and image analysis will be carried out. The concentration of cisplatin in tumor tissue at the beginning and end of mild hyperthermia PITHAC will be evaluated by Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS) that will allow visualization of cisplatin distribution and penetration in tumor biopsies. The correlation between cisplatin concentration and penetration into tumor tissue and clinical response will be explored. Immune infiltration in tumor tissues will be assessed by immunostainings and image analysis will be performed. Immune cells proportions in peripheral blood before and after PITHAC at D0, 10 and 30 will be explored using DURAClone Panels for flow cytometry.
PART B: Expansion: Determination of Sample Size: the sample in the expansion phase is not based on a formal hypothesis. To evaluate the safety of cisplatin administered by PITHAC at the RD and undertake an initial evaluation of efficacy, a total of 15 patients will be enrolled in this exploratory part of the study. Statistical criteria of termination of trial: there are no statistical criteria of termination of the trial in this part of the study.
Primary Analysis: dose limiting toxicities; To determine the maximum tolerated dose (MTD) of cisplatin administered with PITHAC, the primary study outcome is the occurrence of Dose Limiting Toxicities (DLT). The number and proportion of patients with DLTs will be presented overall and by dose and will be plotted vs dose. The MTD will be graphically displayed. Secondary Analyses: safety profile of cisplatin administered with PITHAC: The safety analysis will be performed on the safety population. -Treatment emergent AE frequencies will be summarised by system organ class and preferred term (MedDRA) overall and by dose. AEs will also be tabulated by system organ class and preferred term including maximum severity grade according to the NCI-CTCAE criteria version 5 and relationship to treatment. Incidence of treatment discontinuations due to AEs and SAEs will be summarised overall and by dose. -Safety Lab parameters and vital signs at pre-treatment and post-treatment and corresponding changes from pre-treatment will be presented by dose as descriptive statistics. Efficacy analysis will be performed on efficacy population. Dyspnoea will be scored from screening to D30. Dyspnoea score will be presented at pre- and post-treatment and change from pre- to post-treatment will be presented as descriptive statistics by dose. The pleural infusion index will be determined by comparing chest X-rays before treatment (D0) and post-treatment at D1, D10 and 30 days and pleurodesis or indwelling catheter placement. The index will be presented at pre- and post-treatment and change from pre- to post-treatment will be presented as descriptive statistics by dose. Exploratory endpoints: exploratory analyses will be performed by tissue immunostaining and image analysis will be carried out. The concentration of cisplatin in tumor tissue at the beginning and end of mild hyperthermia PITHAC will be evaluated by Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS) that will allow visualization of cisplatin distribution and penetration in tumor biopsies. The correlation between cisplatin concentration and penetration into tumor tissue and clinical response will be explored. Immune infiltration in tumor tissues will be assessed by immunostainings and image analysis will be performed. Immune cells proportions in peripheral blood before and after PITHAC at D0, 10 and 30 will be explored using DURAClone Panels for flow cytometry.
QUALITY ASSURANCE AND CONTROL: all data collected will be coded and recorded on the RedCap search software. The conformity of eCRF with protocol specifications is checked and validated by the SI and/or qualified individuals, according to ICH GCP. Case Report Forms (eCRF): electronic data entry will be performed via a web-based application (REDCap). Security passwords will be provided to each properly trained investigator. An eCRF for data collection will be developed in Redcap. The REDCap database will record the data obtained with the coding number specific to each patient: this code will consist of PITHAC-01, PITHAC-02 etc…. A specific subject identification log will be compiled to record the identifying information of enrolled participants, providing the link to individual attributed codes. This document (word file) will be kept separately, it will be password protected and saved in a secure directory on a CHUV server. At the end of the project, the subject identification log will be kept by the principal investigator. Best practices will be adopted to ensure that data are complete, reliable, and processed correctly, thus providing high-quality data, keeping the number of errors and missing data as low as possible, and gathering a maximum amount of accurate data for analysis. The data collected through RedCap® will be automatically checked by the implementation of data validation rules (e.g., data-type, maximum/minimum range, missing data checks, and other logical tests) and automatic alerts. Specification of source documents: study monitors will perform ongoing source data verification to confirm that critical protocol data (i.e., source data) entered into the eCRFs by authorized site personnel are accurate, complete, and verifiable from source documents. Source documents (paper or electronic) are those in which patient data are recorded and documented for the first time. They include, but are not limited to, hospital records, clinical and office charts, laboratory notes, memoranda, evaluation checklists, pharmacy dispensing records, recorded data from automated instruments, copies of transcriptions that are certified after verification as being accurate and complete, X-rays, patient files, and records kept at pharmacies, laboratories, and medico-technical departments involved in the clinical trial. The Investigator must keep a subject file (medical file, original medical records) electronically (SOARIAN/ARCHIMEDE) for every subject included in the trial. All documents containing source data must be filed in the electronic patient file. Electronic subject files (SOARIAN/ARCHIMEDE) will be accessible to the Monitor to perform source data verification. Record keeping / archiving: the SI will retain copies of the patient trial records (CRFs, patient informed consent statement, drug inventory logs and all other information collected during the trial) and documentation until at least 10 years after the termination of the trial.It must be available for review by the Monitor and must be ready for Sponsor audit as well as for inspection by Competent Authorities during and after the trial and must be safely archived for at least 10 years (or per local requirements or as otherwise notified by the Sponsor) after the end of the trial. The documents to be thus archived include the Subject Identification List and the signed subject ICFs.
Safety Monitoring (Dose Escalation Part): a Trial Safety Board (TSB) will be constituted for the part A of the trial, being responsible for maintaining the scientific integrity of the trial and safety of patients. This Board will review the DLTs of each cohort and decide whether to escalate or not to the next dose level (next cohort). Details on the dose escalation design, rules, and the role of the TSB are provided in the DEP. The TSB will give the green light to start part B after recommended dose confirmation, based on safety and efficacy data of all patients enrolled in part A. For Part B, the responsibility for the safety of the individual patient lies with the investigator and the SI. Clinical Trial Monitoring: clinical monitoring activities have the ultimate purpose to guarantee that the rights and well-being of human subjects are protected, that the reported study data are accurate, complete and verifiable from source documents, and that the conduct of the study complies with the latest approved version of the study protocol, with ICH-GCP guidelines and applicable regulations .
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- Open-label, non-randomised monocentric Phase I clinical trial study with cisplatin dose escalation administered by PITHAC.
| Arm | Type | Receives |
|---|---|---|
| Cohorte 1 _ 7.5 mg/m2 | Experimental | Drug: Cisplatine Teva®cohorte 1: 7.5 mg/m2 of cisplatin (once) |
| Cohorte 2 _ 12.5 mg/m2 | Experimental | Drug: Cisplatine Teva®cohorte 2: 12.5 mg/m2 of cisplatin (once) |
| cohorte 3: 35 mg/m2 of cisplatin | Experimental | Drug: Cisplatine Teva®cohorte 3: 35 mg/m2 of cisplatin (once) |
| cohorte 4: 70 mg/m2 of cisplatin | Experimental | Drug: Cisplatine Teva®cohorte 4: 70 mg/m2 of cisplatin (once) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- At least 18 years of age
- Body weight at least 30 kg
- Eastern cooperative oncology group performance status score of 0-2 at enrolment
- Patient with pleural carcinosis that qualify for a surgical intervention for pleurodesis or placement of an indwelling permanent catheter.
- Life expectancy of at least 3 months
Key exclusion criteria (23 listed)
- Patients with active or chronic hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test at pre-screening)
- Patients with active hepatitis C
- Any known formal contra-indication for video-assisted thoracoscopy (VATS) according to pulmonary and cardiac preliminary investigations.
- Systemic cytotoxic anticancer treatment within 10 days before and after enrolment except for inhibitors of vascular endothelial growth factor for which this period should be decided according to the used drug (for bevacizumab the period involves 4 weeks before and after enrolment, for lenvatinib 1 week before and 2 weeks after, and for sorafenib 1 week before and after), no limitations applied for immune checkpoint inhibitors
- Major surgery within 28 days prior to enrolment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cisplatine Teva®Also: Procedure/SurgeryPITHAC: Cisplatin (Cisplatine Teva®) at a dose between 7.5 and 70 mg/m2 of body surface at a temperature of 39±1°C | Drug | Cohorte 1 _ 7.5 mg/m2, Cohorte 2 _ 12.5 mg/m2, cohorte 3: 35 mg/m2 of cisplatin, cohorte 4: 70 mg/m2 of cisplatin |
Primary outcome
Dose Escalation and Maximum Tolerated Dose determination (Part A):
Time frame: 18 months approximately
In order to determine the maximum tolerated dose (MTD) of cisplatin administered by PITHAC, the primary study outcome will be the occurrence of Dose Limiting Toxicities (DLT).
Expansion phase (Part B):
Time frame: between 10 and 12 months
Safety profile of cisplatin administered by PITHAC will be assessed by the incidence of Adverse Events and Serious Adverse Events according to NCI-CTCAE criteria (v5). Incidence and severity of intraoperative and post-operative complications will be measured using the Clavien-Dindo classification up to 30 days after the intervention. Safety profile of cisplatin administered by PITHAC will be assessed by the incidence of Adverse Events and Serious Adverse Events according to NCI-CTCAE criteria (v5). Incidence and severity of intraoperative and post-operative complications will be measured using the Clavien-Dindo classification up to 30 days after the intervention.
2 secondary outcomes
Dose Escalation and MTD determination (Part A):
Time frame: 18 months
Expansion phase (Part B):
Time frame: 10 /12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2024.
- Derived from this study: PubMed 39708537Chriqui LE, Abdelnour-Berchtold E, Zanfrini E, Devesa-Perez S, Gonzalez M, Krueger T, Ellefsen K, Destaillats A, Bonnet D, Hubner M, Bouchaab H, Bassani-Sternberg M, Peters S, Cavin S, Perentes JY. Phase I clinical trial testing the dose escalation and expansion of Pressurized IntraThoracic Hyperthermic Aerosol Cisplatin administration (PITHAC) for the management of pleural carcinosis. Cancer Treat Res Commun. 2024;42:100858. doi: 10.1016/j.ctarc.2024.100858. Epub 2024 Dec 17.
Related trials for Mesothelioma, Malignant
RecruitingPhase 1
Anti-Mesothelin TNaive/SCM hYP218 (TNhYP218) CAR T Cells in Participants With Mesothelin-Expressing Solid Tumors Including Mesothelioma
Mesothelioma, Neoplasms
RecruitingObservational study
Tissue Procurement and Natural History Study of Patients With Malignant Mesothelioma
Thymoma, Stomach Neoplasms
RecruitingPhase 1
Individual Response to Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Treatment of Peritoneal Carcinomatosis From Peritoneal Mesothelioma or Atypical Mesothelial Proliferation or From Ovarian, Colorectal, or Appendiceal Histologies
Peritoneal Mesothelioma, Peritoneal Carcinomatosis
RecruitingPhase 1/2
A 2-part Phase 1/2 Open-label Trial on ODM-212
Mesothelioma, Pancreatic Cancer
RecruitingPhase 1/2
Rinatabart Sesutecan (Rina-S, PRO1184, GEN1184) for Advanced Solid Tumors (GCT1184-01/ PRO1184-001)
High Grade Epithelial Ovarian Cancer, High Grade Serous Ovarian Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jean-Yannis Perentes principal investigator
Centre Hospitalier Universitaire Vaudois
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cisplatine Teva® in people with Mesothelioma, Malignant and Carcinoma, Non-Small-Cell Lung, run by Dr Jean Yannis PERENTES at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 28 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jean-Yannis H Perentes (0795560876, jean.perentes@chuv.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose Escalation and Maximum Tolerated Dose determination (Part A): (time frame: 18 months approximately). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06281860, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2024.