Clinical Trials /

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

NCT04187404

Description:

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.

Related Conditions:
  • Adrenal Cortex Carcinoma
  • Adrenal Gland Pheochromocytoma
  • Paraganglioma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Novel Therapeutic Vaccine (EO2401) in Metastatic Adrenocortical Carcinoma, or Malignant Pheochromocytoma/Paraganglioma
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: EOADR1-19
  • NCT ID: NCT04187404

Conditions

  • Adrenocortical Carcinoma
  • Pheochromocytoma
  • Paraganglioma

Interventions

DrugSynonymsArms
EO24015-cohort study design

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
5-cohort study designExperimentalCohort 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.
  • EO2401

Eligibility Criteria

        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 high
             ki-67 expression in tumor (≥ 20%), and unresectable primary tumor.

          6. Patients with ACC and uncontrolled cortisol 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Adverse events assessment
Time Frame:Up to 24 months
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Evaluation of survival
Time Frame:From end of treatment to at least 24 months after last patient enrollment
Safety Issue:
Description:Overall survival, defined as the time interval from the date of first study treatment administration to the date of death due to any cause
Measure:Assessment of the immunogenicity
Time Frame:Up to 24 months
Safety Issue:
Description:Assessment of the immunogenicity of the 4 components that compose EO2401 Immunogenicity will be assessed by Interferon-γ ELISpot

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Enterome

Trial Keywords

  • adrenocortical carcinoma
  • pheochromocytoma
  • paraganglioma

Last Updated

December 5, 2019