Treatment for pleural carcinosis using heated aerosol chemotherapy

Phase I Clinical Trial Testing the Dose Escalation and Expansion of Pressurized IntraThoracic Hyperthermic Aerosol Cisplatin Administration for the Management of Pleural Carcinosis

This study is testing a new heated aerosol chemotherapy treatment for people with pleural carcinosis to see how safe it is and what the best dose is.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 39 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Centre Hospitalier Universitaire Vaudois (other)
• Drugs / interventions: bevacizumab, lenvatinib
• Locations: 1 site (Lausanne)
• Trial ID: NCT06281860 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the safety and maximum tolerated dose of pressurized intra-thoracic hyperthermic aerosol cisplatin administration in patients with pleural carcinosis. The study includes a dose escalation phase followed by an expansion phase at the recommended dose. Participants will undergo various assessments, including chest X-rays, blood tests for pharmacokinetics and immune profiling, and tissue biopsies to evaluate the treatment's effects. The primary focus is on monitoring adverse events and the overall safety of the treatment.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with confirmed pleural carcinosis and a life expectancy of at least three months.

Not a fit: Patients with a performance status score above 2 or those not qualifying for surgical intervention may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced cancers affecting the pleura.

How similar studies have performed: While this approach is novel, similar studies using hyperthermic aerosol chemotherapy have shown promise in treating other malignancies.

Eligibility criteria

Inclusion Criteria:

* 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)
* 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

Exclusion Criteria:

* 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
* 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

Where this trial is running

Lausanne

• Centre Hospitalier Universitaire Vaudois — Lausanne, Switzerland (RECRUITING)

Study contacts

• Principal investigator: Jean-Yannis Perentes — Centre Hospitalier Universitaire Vaudois
• Study coordinator: Jean-Yannis H Perentes

Conditions: Mesothelioma, Malignant, Carcinoma, Non-Small-Cell Lung, Carcinoma Breast Stage IV, Ovarian Cancer, Esophageal Cancer, Gastric Cancer, Pressurized intrathoracic hyperthermic aerosol chemotherapy