A phase 1 clinical trial for the treatment of patients with inoperable mesothelioma, with both pembrolizumab immunotherapy and cryoablation, has begun in New Jersey and New York, USA. Starting 24 September 2021, the trial is expected to be completed by September 2023.
Pembrolizumab immunotherapy enhances the ability of the immune system to detect and kill cancer cells. In patients with inoperable mesothelioma in the chest of the abdomen, researchers are trialing the addition of cryoablation within a phase 1 trial. Cryoablation uses extreme cold applied through the needle into a tumour to break down and kill cancer cells. Researcher Micheal Offin and co-investigators Marjorie Zaudere and Etay Ziv (all Memorial Sloan Kettering Cancer Centre, New York, USA) have therefore begun to investigate the treatment impact of drugs that strengthen the immune system such as pembrolizumab, plus cryoablation for inoperable mesothelioma.
This single group assessment is designed as a single-arm and single-institution study, with an estimated 10 patients recruited. All patients must be over the age of 18 and have pleural or peritoneal mesothelioma that continues to grow despite previous treatment. Eligible patients must be fully capable of self-care, with the exception of carrying out strenuous activities. Patients who have received one previous line of systemic therapy which did not include pembrolizumab, are eligible for the study unless treated one year or more from the trial enrollment. Patients must also present a Karnofsky Performance Score (KPS) of ≤70% with adequate organ function. The criteria for adequate organ function is shown below:
- Absolute neutrophil count ≥1.5K/mcL
- Platelet count ≥100K/mcL
- Adequate renal function as defined as creatinine ≤1.5x upper limit of normal (ULN) or creatinine clearance ≥45ml/min (as calculated by Cockcroft-Gault Formula)
- Haemoglobin ≥ 9g/dL (prior transfusion permitted if not within seven days of enrolment)
- Total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) range
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤3.0 × ULN or AST
Eligible patients will receive one cycle of pembrolizumab (200mg/dose) delivered intravenously, followed by image-guided cryoablation of an ablation index lesion which will occur one to seven days prior to the start of cycle two. Cryoablation will treat a lesion with preference given to a lesion that is symptomatic or at risk of causing symptoms. Following institutional standards, complete ablation will be attempted. In addition, pembrolizumab will be continued for up to 24 months, unless disease progression, or intolerable toxicity. The number of patients with an adverse event defined as grade three or higher non-haematologic toxicity within 12 weeks of cryoablation will be the primary outcome measure.