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

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ClinicalTrials.gov Identifier: NCT05563467
Recruitment Status : Not yet recruiting
First Posted : October 3, 2022
Last Update Posted : October 3, 2022
Sponsor:
Collaborator:
Biostat Sp. z o.o.
Information provided by (Responsible Party):
Maria Sklodowska-Curie National Research Institute of Oncology

Study Description
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Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Adrenocortical Carcinoma Drug: Pembrolizumab 25 MG/ML [Keytruda] Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicentre, Open-label Phase 2 Study to Evaluate the Efficacy and Safety of Pembrolizumab in the Treatment of Advanced, Progressive Adrenocortical Carcinoma.
Estimated Study Start Date : December 1, 2022
Estimated Primary Completion Date : May 31, 2027
Estimated Study Completion Date : May 31, 2027

Resource links provided by the National Library of Medicine


Arms and Interventions
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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.


Outcome Measures
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Primary Outcome Measures :
  1. Objective Response Rate [ Time Frame: through study completion, an average of 4 years ]
    Percentage of patients who achieved a partial (PR) or complete (CR) response to treatment.

  2. Progression-Free Survival (PFS) [ Time Frame: through study completion, an average of 4 years ]
    Time from first dose of treatment until disease progression or death from any cause.

  3. Duration of Response (DoR) [ Time Frame: through study completion, an average of 4 years ]
    Duration of response to treatment (from the start of CR or PR) until disease progression or death from any cause.

  4. Overall Survival (OS) [ Time Frame: through study completion, an average of 4 years ]
    Time from initiating treatment to death from any cause.


Secondary Outcome Measures :
  1. Number of Adverse Events and Serious Adverse Events (AE and SAE) [ 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.

  2. Quality of life assessed based on the QLQ-C30 questionnaire. [ 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.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05563467


Contacts
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Contact: Barbara Ziółkowska, MD,PhD 32-278-88-22 ext 0048 barbara.ziolkowska@io.gliwice.pl
Contact: Agnieszka Kotecka-Blicharz, MD

Sponsors and Collaborators
Maria Sklodowska-Curie National Research Institute of Oncology
Biostat Sp. z o.o.
More Information
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Responsible Party: Maria Sklodowska-Curie National Research Institute of Oncology
ClinicalTrials.gov Identifier: NCT05563467    
Other Study ID Numbers: PEMBR-01
First Posted: October 3, 2022    Key Record Dates
Last Update Posted: October 3, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Maria Sklodowska-Curie National Research Institute of Oncology:
advanced adrenocortical carcinoma
progressive adrenocortical carcinoma
pembrolizumab
Additional relevant MeSH terms:
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Carcinoma
Adrenocortical Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Adrenal Cortex Neoplasms
Adrenal Gland Neoplasms
 Endocrine Gland Neoplasms
Neoplasms by Site
Adrenal Cortex Diseases
Adrenal Gland Diseases
Endocrine System Diseases
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents