Pembrolizumab in the Treatment of Advanced, Progressive Adrenocortical Carcinoma. (PEMBR-01)

March 28, 2025 updated by: Maria Sklodowska-Curie National Research Institute of Oncology

A Multicentre, Open-label Phase 2 Study to Evaluate the Efficacy and Safety of Pembrolizumab in the Treatment of Advanced, Progressive Adrenocortical Carcinoma.

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

24

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Agnieszka Kotecka-Blicharz, MD

Study Locations

  • Poland
      • Cracow, Poland
        • Recruiting
        • Samodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie
        • Contact:
        • Contact:
          • Marcin Motyka, MD, PhD
      • Poznań, Poland
        • Recruiting
        • Uniwersytecki Szpital Kliniczny w Poznaniu
        • Contact:
        • Contact:
          • Marek Ruchała, Prof.
      • Warsaw, Poland
        • Recruiting
        • Medical University of Warsaw
        • Contact:
        • Contact:
          • Urszula Ambroziak, MD, PhD
    • Śląskie
      • Gliwice, Śląskie, Poland, 44-102
        • Recruiting
        • Maria Sklodowska-Curie National Research Institute of Oncology
        • Contact:
          • Agnieszka Kotecka-Blicharz, MD
        • Contact:
          • Tomasz Lachcik, M.Sc.
          • Phone Number: 0048 322789791
        • Contact:
          • Barbara Ziółkowska, MD,PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Signing the informed consent form to participate in the study
  2. Age over 18 years of age
  3. Histopathologically confirmed adrenocortical carcinoma
  4. The general condition of the patient was assessed according to the Eastern Cooperative Oncology Group (ECOG) scale <2
  5. Measurable disease according to RECIST 1.1
  6. Confirmed progression according to RECIST 1.1 within the last 6 months in patients, who received at least one line chemotherapy according to the EDP or EDP-M

  7. Adequate function of the marrow and internal organs:

    1. hemoglobin ≥ 9g%, neutrophils> 1500 / mm3, platelets> 100 thousand / mm3
    2. bilirubin ≤ 2 x upper limit of normal (UNL), Alat, Aspat ≤ 3 x UNL (if livermetastases are present ≤ 5 x UNL)
    3. creatinine clearance > 40 ml / min
    4. coagulation parameters: INR, PT, APTT <1.5 x UNL (exception: patients undergoing anticoagulation therapy, where INR, PT, APTT remain within the therapeutic range recommended for the patient)
  8. For women of reproductive age : confirmed negative pregnancy test result, and the requirement of dual barrier contraception
  9. For men of reproductive age: the requirement of dual barrier contraception

Exclusion Criteria:

  1. Pre-treatment with an immune checkpoint inhibitor
  2. Any cancer therapy within the last 7 days (including mitotane)
  3. Persistent side effects of previous anti-cancer therapy in the> G1 stage or after surgical treatment (exception: alopecia)
  4. Immunosuppressive therapy present or conducted within the last 4 weeks
  5. Glucocorticoid therapy in a dose higher than the replacement dose (subject to the permitted use: inhaled or topical steroids, single administration of a steroid, e.g. in case of an allergic reaction to contrast, use of mineralocorticosteroids, steroids in the course of asthma or COPD)
  6. Previous allograft marrow or organ transplant
  7. Current or diagnosed in the last 2 years autoimmune disease with the exception of vitiligo, psoriasis not requiring systemic treatment, autoimmune disease of the thyroid gland
  8. Active or previously documented inflammatory disease of the large intestine
  9. Previous non-infectious pneumonia requiring steroid therapy
  10. Hepatitis B or C
  11. Active tuberculosis
  12. Current active infection requiring systemic treatment
  13. Symptomatic, untreated central nervous system (CNS) metastases (exception: patients with asymptomatic CNS metastases with prior surgery or radiotherapy and no history of intracranial bleeding)
  14. Circulatory failure NYHA ≥3
  15. Corrected QT interval> 500 ms
  16. Significant coexisting disease, including neoplastic, except for basal cell carcinoma of the skin, carcinoma in situ: prostate, cervix, breast
  17. Other significant comorbid disease that, in the investigator's opinion, would pose risks to the patient during therapy
  18. Pregnancy or breastfeeding
  19. Patients requiring dialysis
  20. The patient's inability to meet the requirements specified in the study protocol
  21. Vaccination with live vaccine within 3 months before starting treatment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pembrolizumab Treatment
Drug: Pembrolizumab 25 MG/ML [Keytruda]
The 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assessment of the effectiveness of pembrolizumab (Keytruda) in the treatment of advanced, progressive adrenocortical carcinoma.
Time Frame: through study completion, an average of 4 years
Outcome will be assessed based on i.a. objective response rate (ORR).
through study completion, an average of 4 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assessment of the safety of pembrolizumab (Keytruda) in the treatment of advanced, progressive adrenocortical carcinoma.
Time Frame: through study completion, an average of 4 years
Number of Adverse Events and Serious Adverse Events (AE and SAE) related and not related to treatment according to CTCAE.
through study completion, an average of 4 years
Assessment of the impact of therapy on the patient's quality of life.
Time Frame: through study completion, an average of 4 years
Quality of life assessed based on the QLQ-C30 questionnaire in which patients will respond during the clinical trial.
through study completion, an average of 4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Maria Sklodowska-Curie National Research Institute of Oncology

Collaborators

Biostat Sp. z o.o.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 31, 2023

Primary Completion (Estimated)

May 31, 2027

Study Completion (Estimated)

May 31, 2027

Study Registration Dates

First Submitted

August 23, 2022

First Submitted That Met QC Criteria

September 29, 2022

First Posted (Actual)

October 3, 2022

Study Record Updates

Last Update Posted (Actual)

April 2, 2025

Last Update Submitted That Met QC Criteria

March 28, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PEMBR-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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