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A Novel Therapeutic Vaccine (EO2401) in Metastatic Adrenocortical Carcinoma, or Malignant Pheochromocytoma/Paraganglioma (Spencer)

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ClinicalTrials.gov Identifier: NCT04187404
Recruitment Status : Recruiting
First Posted : December 5, 2019
Last Update Posted : July 19, 2021
Sponsor:
Information provided by (Responsible Party):
Enterome

Tracking Information
First Submitted Date  ICMJE December 3, 2019
First Posted Date  ICMJE December 5, 2019
Last Update Posted Date July 19, 2021
Actual Study Start Date  ICMJE July 23, 2020
Estimated Primary Completion Date May 30, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 5, 2019)
Adverse events assessment [ Time Frame: Up to 24 months ]
Incidences of adverse events(AEs), treatment-emergent AEs (TEAEs), Serious Adverse Events ( SAEs), deaths, and laboratory abnormalities using the National Cancer Institute-Common Terminology Criteria for AEs (NCI-CTCAE) v5.0.
Original Primary Outcome Measures  ICMJE
 (submitted: December 4, 2019)
Safety and tolerability [ Time Frame: Up to 24 months ]
Incidences of adverse events(AEs), treatment-emergent AEs (TEAEs), Serious Adverse Events ( SAEs), deaths, and laboratory abnormalities using the National Cancer Institute-Common Terminology Criteria for AEs (NCI-CTCAE) v5.0.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 4, 2019)
  • Evaluation of survival [ Time Frame: From end of treatment to at least 24 months after last patient enrollment ]
    Overall survival, defined as the time interval from the date of first study treatment administration to the date of death due to any cause
  • Assessment of the immunogenicity [ Time Frame: Up to 24 months ]
    Assessment of the immunogenicity of the 4 components that compose EO2401 Immunogenicity will be assessed by Interferon-γ ELISpot
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Novel Therapeutic Vaccine (EO2401) in Metastatic Adrenocortical Carcinoma, or Malignant Pheochromocytoma/Paraganglioma
Official Title  ICMJE A Phase 1/2 Trial of a Novel Therapeutic Vaccine (EO2401) in Combination With Immune Check Point Blockade, for Treatment of Patients With Locally Advanced or Metastatic Adrenocortical Carcinoma, or Malignant Pheochromocytoma/Paraganglioma
Brief Summary This is a multicenter, Phase 1/2, First-In-Human study to assess the safety, tolerability, immunogenicity, and preliminary efficacy of EO2401 in Metastatic Adrenocortical Carcinoma, or Malignant Pheochromocytoma/Paraganglioma.
Detailed Description EO2401 is an innovative cancer peptide therapeutic vaccine based on the homologies between Tumor Associated Antigens and microbiome-derived peptides that will be administered in combination with nivolumab to generate preliminary safety and efficacy data in patients with Metastatic Adrenocortical Carcinoma, or Malignant Pheochromocytoma/Paraganglioma.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Adrenocortical Carcinoma
  • Pheochromocytoma
  • Paraganglioma
Intervention  ICMJE Biological: EO2401
Multiple dose of EO2041 in combination with nivolumab
Study Arms  ICMJE Experimental: 5-cohort study design

Cohort 1:3-by-3 design of EO2401 in combination with nivolumab at standard dose. Three to 12 evaluable patients with adrenal carcinoma or progressive malignant pheochromocytoma/paraganglioma will be included depending on the safety profile of the administered treatments.

Cohorts 2A (previously treated patients) and 2B (previously untreated patients): evaluation of EO2401 at the recommended dose found in Cohort 1 in combination with nivolumab in 30 evaluable patients (15 each for Cohorts 2A and 2B) with adrenal carcinoma.

Cohorts 3A (previously treated patients) and 3B (previously untreated patients) : evaluation of EO2401 at the recommended dose found in Cohort 1 in combination with nivolumab in 30 evaluable patients (15 each for Cohorts 3A and 3B) with progressive malignant pheochromocytoma/paraganglioma.

Intervention: Biological: EO2401
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 17, 2020)
60
Original Estimated Enrollment  ICMJE
 (submitted: December 4, 2019)
72
Estimated Study Completion Date  ICMJE March 30, 2024
Estimated Primary Completion Date May 30, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Main Inclusion Criteria:

  1. For inclusion in Cohort 1 patients should have adrenocortical carcinoma(ACC), or malignant pheochromocytoma/paraganglioma (MPP), as defined below for Cohorts 2A and 3A.
  2. For inclusion in Cohorts 2A and 2B patients should have histologically confirmed (at primary diagnosis) unresectable locally advanced or metastatic adrenocortical carcinoma.
  3. For inclusion in Cohorts 3A and 3B patients should have histologically confirmed (at primary diagnosis) unresectable malignant (defined as metastatic disease, i.e. presence of chromaffin tissue in non-chromaffin organs) pheochromocytoma/paraganglioma, and RECIST defined progression should have been documented during a maximum of an 18-months period.
  4. Patients with an age ≥ 18 years old.
  5. Patients who are human leukocyte antigen (HLA)-A2 positive.
  6. Patients with an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
  7. Patients with a life expectancy > 4 months as judged by their treating physician.
  8. Patients with at least one measurable lesion according to RECIST 1.1.
  9. Males or non-pregnant, non-lactating, females.
  10. Patients willing and able to comply with the scheduled visits, treatment plan, laboratory tests, and other study procedures indicated in the protocol.
  11. Patients having received the information sheet and who have provided written informed consent prior to any study-related procedures.

Main Exclusion Criteria:

  1. Patients treated with dexamethasone > 2 mg/day or equivalent (i.e. 13 mg/day of prednisone, or 53 mg/day of hydrocortisone) within 14 days before the first EO2401 administration, unless required to treat an adverse event.
  2. Patients with prior treatment with immune check-point inhibitors
  3. Patients with prior exposure to EO2401.
  4. Patients treated with immunotherapy (meaning immunostimulatory or immunosuppressive therapy; beside excluded, or allowed, compounds per other inclusion/exclusion criteria specifications), radionuclide therapy, radiotherapy, cytoreductive therapy, or received treatment with any other investigational agent within 28 days before the first EO2401 administration.
  5. Patients with ACC with more than three organs involved by disease, combined with unresectable primary tumor.
  6. Patients with ACC and uncontrolled hormonal secretion (according to the judgement of the treating physician).
  7. Patients with MPP and uncontrolled blood pressure (according to the judgement of the treating physician).
  8. Patients with abnormal laboratory values.
  9. Patients with persistent Grade 3 or 4 toxicities.
  10. Uncontrolled central nervous system (CNS) metastasis.
  11. Other malignancy or prior malignancy with a disease-free interval of less than 3 years
  12. Patients with clinically significant disease.
  13. Patients with suspected autoimmune or active autoimmune disorder or known history of an autoimmune neurologic condition (e.g. Guillain-Barré syndrome).
  14. Patients with history of solid organ transplantation or hematopoietic stem cell transplantation.
  15. Patients with history or known presence of tuberculosis.
  16. Pregnant and breastfeeding patients.
  17. Patients with history or presence of human immunodeficiency virus and/or potentially active hepatitis B virus/hepatitis C virus infection.
  18. Patients who have received live or attenuated vaccine therapy used for prevention of infectious diseases including seasonal (influenza) vaccinations within 4 weeks of the first dose of study drug.
  19. Patients with a history of hypersensitivity to any excipient present in the pharmaceutical forms of the study treatments.
  20. Patients treated with herbal remedies with immunostimulating properties or known to potentially interfere with major organ function.
  21. Patients with known ongoing drug and alcohol abuse.
  22. Patients with known or underlying medical or psychiatric condition that, in the Investigator's opinion, would make the administration of study drug hazardous to the patient or obscure the interpretation of toxicity determination or AEs.
  23. Patients deprived of their liberty, under protective custody, or guardship.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Gender Based Eligibility: Yes
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Muriel Habibian +33 1 76 21 58 16 mhabibian@enterome.com
Listed Location Countries  ICMJE Denmark,   France,   Germany,   Italy,   Netherlands,   Spain,   Sweden,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04187404
Other Study ID Numbers  ICMJE EOADR1-19
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Enterome
Study Sponsor  ICMJE Enterome
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Jan Fagerberg Enterome
PRS Account Enterome
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP