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

Primary Purpose

Adrenocortical Carcinoma

Status
Recruiting
Phase
Phase 2
Locations
Poland
Study Type
Interventional
Intervention
Pembrolizumab 25 MG/ML [Keytruda]
Sponsored by
Maria Sklodowska-Curie National Research Institute of Oncology
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adrenocortical Carcinoma focused on measuring advanced adrenocortical carcinoma, progressive adrenocortical carcinoma, pembrolizumab

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Maria Sklodowska-Curie National Research Institute of OncologyRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Pembrolizumab Treatment

Arm Description

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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.

Full Information

First Posted
August 23, 2022
Last Updated
March 3, 2023
Sponsor
Maria Sklodowska-Curie National Research Institute of Oncology
Collaborators
Biostat Sp. z o.o.
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1. Study Identification

Unique Protocol Identification Number
NCT05563467
Brief Title
Pembrolizumab in the Treatment of Advanced, Progressive Adrenocortical Carcinoma.
Acronym
PEMBR-01
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.
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 31, 2023 (Actual)
Primary Completion Date
May 31, 2027 (Anticipated)
Study Completion Date
May 31, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Maria Sklodowska-Curie National Research Institute of Oncology
Collaborators
Biostat Sp. z o.o.

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adrenocortical Carcinoma
Keywords
advanced adrenocortical carcinoma, progressive adrenocortical carcinoma, pembrolizumab

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Pembrolizumab Treatment
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab 25 MG/ML [Keytruda]
Intervention Description
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.
Primary Outcome Measure Information:
Title
Assessment of the effectiveness of pembrolizumab (Keytruda) in the treatment of advanced, progressive adrenocortical carcinoma.
Description
Outcome will be assessed based on i.a. objective response rate (ORR).
Time Frame
through study completion, an average of 4 years
Secondary Outcome Measure Information:
Title
Assessment of the safety of pembrolizumab (Keytruda) in the treatment of advanced, progressive adrenocortical carcinoma.
Description
Number of Adverse Events and Serious Adverse Events (AE and SAE) related and not related to treatment according to CTCAE.
Time Frame
through study completion, an average of 4 years
Title
Assessment of the impact of therapy on the patient's quality of life.
Description
Quality of life assessed based on the QLQ-C30 questionnaire in which patients will respond during the clinical trial.
Time Frame
through study completion, an average of 4 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Measurable disease according to RECIST 1.1 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 Adequate function of the marrow and internal organs: hemoglobin ≥ 9g%, neutrophils> 1500 / mm3, platelets> 100 thousand / mm3 bilirubin ≤ 2 x upper limit of normal (UNL), Alat, Aspat ≤ 3 x UNL (if livermetastases are present ≤ 5 x UNL) creatinine clearance > 40 ml / min 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) For women of reproductive age : confirmed negative pregnancy test result, and the requirement of dual barrier contraception For men of reproductive age: the requirement of dual barrier contraception Exclusion Criteria: 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 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) Previous allograft marrow or organ transplant 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 Active or previously documented inflammatory disease of the large intestine Previous non-infectious pneumonia requiring steroid therapy Hepatitis B or C Active tuberculosis Current active infection requiring systemic treatment Symptomatic, untreated central nervous system (CNS) metastases (exception: patients with asymptomatic CNS metastases with prior surgery or radiotherapy and no history of intracranial bleeding) Circulatory failure NYHA ≥3 Corrected QT interval> 500 ms Significant coexisting disease, including neoplastic, except for basal cell carcinoma of the skin, carcinoma in situ: prostate, cervix, breast Other significant comorbid disease that, in the investigator's opinion, would pose risks to the patient during therapy Pregnancy or breastfeeding Patients requiring dialysis The patient's inability to meet the requirements specified in the study protocol Vaccination with live vaccine within 3 months before starting treatment
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Barbara Ziółkowska, MD,PhD
Phone
32-278-88-22
Ext
0048
Email
barbara.ziolkowska@io.gliwice.pl
First Name & Middle Initial & Last Name or Official Title & Degree
Agnieszka Kotecka-Blicharz, MD
Facility Information:
Facility Name
Maria Sklodowska-Curie National Research Institute of Oncology
City
Gliwice
State/Province
Śląskie
ZIP/Postal Code
44-102
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tomasz Lachcik, M.Sc.
Phone
322789791
Ext
0048
First Name & Middle Initial & Last Name & Degree
Barbara Ziółkowska, MD,PhD
First Name & Middle Initial & Last Name & Degree
Agnieszka Kotecka-Blicharz, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Pembrolizumab in the Treatment of Advanced, Progressive Adrenocortical Carcinoma.

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