This study is a national, multicenter, interventional, phase II clinical trial on the use of pembrolizumab in advanced adrenocortical carcinoma, with confirmed progression within 6 months, following EDP or EDP-M ( etoposide, doxorubicin, cisplatin- mitotan) chemotherapy.
Adrenocortical carcinoma is a very rare entity with poor prognosis and limited therapeutic options. Only radical surgical treatment of the early stages gives a chance for complete cure, however the risk of recurrence still remains high.
The results of clinical trials conducted outside Poland indicate a possible potential role of immunotherapy as a rescue treatment for adrenocortical carcinoma after standard therapeutic methods have been exhausted.
This study will evaluate the efficacy and tolerability of treatment with the immune checkpoint inhibitor pembrolizumab in locally advanced, non-operable or metastatic adrenocortical carcinoma after first line chemotherapy failure.
The study population will include adult patients (\>18 years of age) with histopathologically confirmed adrenocortical carcinoma and confirmed progression according to RECIST 1.1 within 6 months, after first line chemotherapy with the EDP and EDP-M scheme. Patients must meet the inclusion criteria and must not meet the exclusion criteria described in the PEMBR-01 study protocol. The planned number of patients in the study is 24.
The treatment regimen will be based on Pembrolizumab administered intravenously in 3 weeks cycles at a dose of 200mg. For hormonally active tumors producing cortisol, it is hypothesized that the use of pembrolizumab in combination with effective steroidogenesis inhibition may enhance the effect of immunotherapy. In the study, metyrapone or ketoconazole will be used for this purpose.
The primary endpoint of the study will be the objective response rate to the treatment. The secondary endpoints will be progression-free survival, duration of response, overall survival, and treatment safety as well as the effect of therapy on patients' quality of life.
Concurrently, the analysis of biomarkers in tumor tissue will be carried out, including tumour infiltrating lymphocytes, expression of programmed death ligand, microsatellite instability and tumour mutation burden.
Signing the informed consent form to participate in the study
Age over 18 years of age
Histopathologically confirmed adrenocortical carcinoma
The general condition of the patient was assessed according to the Eastern Cooperative Oncology Group (ECOG) scale <2
Pre-treatment with an immune checkpoint inhibitor
Any cancer therapy within the last 7 days (including mitotane)
Persistent side effects of previous anti-cancer therapy in the> G1 stage or after surgical treatment (exception: alopecia)
Immunosuppressive therapy present or conducted within the last 4 weeks
Single group
Pembrolizumab 25 MG/ML [Keytruda]
DrugThe treatment scheme will be based on pembrolizumab administered intravenously in cycles of every 3 weeks 200 mg, with supportive treatment with steroidogenesis inhibitor (metyrapone or ketoconazole) for adrenocortical carcinoma producing cortisol.
Assessment of the effectiveness of pembrolizumab (Keytruda) in the treatment of advanced, progressive adrenocortical carcinoma.
Outcome will be assessed based on i.a. objective response rate (ORR).
Assessment of the safety of pembrolizumab (Keytruda) in the treatment of advanced, progressive adrenocortical carcinoma.
Number of Adverse Events and Serious Adverse Events (AE and SAE) related and not related to treatment according to CTCAE.
Assessment of the impact of therapy on the patient's quality of life.
Quality of life assessed based on the QLQ-C30 questionnaire in which patients will respond during the clinical trial.
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Maria Sklodowska-Curie National Research Institute of Oncology
Lead sponsor
Biostat Sp. z o.o.
Collaborator
