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

Primary Purpose

Adrenocortical Carcinoma, Pheochromocytoma, Paraganglioma

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
EO2401
Nivolumab
Sponsored by
Enterome
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adrenocortical Carcinoma focused on measuring adrenocortical carcinoma, pheochromocytoma, paraganglioma

Eligibility Criteria

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

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.

Sites / Locations

  • MD Anderson Cancer CenterRecruiting
  • RigshospitaletRecruiting
  • Chu LilleRecruiting
  • Centre Léon BérardRecruiting
  • Assistance Publique - Hôpitaux de Marseille - Hôpital NordRecruiting
  • Institut Gustave RoussyRecruiting
  • Lmu KlinikumRecruiting
  • Universitätsklinikum WürzburgRecruiting
  • Azienda Ospedaliera Spedali CiviliRecruiting
  • Amsterdam UMC, location VUmcRecruiting
  • Hospital Universitari Vall d'HebronRecruiting
  • Karolinska University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Active Comparator

Arm Label

5-cohort study design

randomized extension of Cohort 2A (3 arms): C2A-I

randomized extension of Cohort 2A (3 arms): C2A-II

randomized extension of Cohort 2A (3 arms): C2A-III

Arm Description

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 EO2401in combination with nivolumab in 33 patients with adrenal carcinoma. Cohorts 3A (previously treated patients) and 3B (previously untreated patients) : evaluation of EO2401 combination with nivolumab in 20 patients (globally for both Cohorts 3A and 3B) with progressive malignant pheochromocytoma/ paraganglioma.

Randomized extension of Cohort 2A (65 patients using a 4:1:1 ratio): 43 patients belonging to this extension of Cohort 2A will be treated by EO2401 and nivolumab in combination.

11 patients belonging to this extension of Cohort 2A will be treated by EO2401 alone.

11 patients belonging to this extension of Cohort 2A who will be treated by nivolumab alone.

Outcomes

Primary Outcome Measures

Adverse events assessment
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

Evaluation of Progression Free Survival at 6 months
Progression Free Survival according to iRECIST criteria defined as the time interval from the date of first study treatment administration to 6 months after
Evaluation of survival
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
Assessment of the immunogenicity of the 4 components that compose EO2401 Immunogenicity will be assessed by Interferon-γ ELISpot

Full Information

First Posted
December 3, 2019
Last Updated
August 24, 2023
Sponsor
Enterome
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1. Study Identification

Unique Protocol Identification Number
NCT04187404
Brief Title
A Novel Therapeutic Vaccine (EO2401) in Metastatic Adrenocortical Carcinoma, or Malignant Pheochromocytoma/Paraganglioma
Acronym
Spencer
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 23, 2020 (Actual)
Primary Completion Date
June 30, 2024 (Anticipated)
Study Completion Date
December 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Enterome

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adrenocortical Carcinoma, Pheochromocytoma, Paraganglioma
Keywords
adrenocortical carcinoma, pheochromocytoma, paraganglioma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
5-cohort study design
Arm Type
Experimental
Arm Description
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 EO2401in combination with nivolumab in 33 patients with adrenal carcinoma. Cohorts 3A (previously treated patients) and 3B (previously untreated patients) : evaluation of EO2401 combination with nivolumab in 20 patients (globally for both Cohorts 3A and 3B) with progressive malignant pheochromocytoma/ paraganglioma.
Arm Title
randomized extension of Cohort 2A (3 arms): C2A-I
Arm Type
Experimental
Arm Description
Randomized extension of Cohort 2A (65 patients using a 4:1:1 ratio): 43 patients belonging to this extension of Cohort 2A will be treated by EO2401 and nivolumab in combination.
Arm Title
randomized extension of Cohort 2A (3 arms): C2A-II
Arm Type
Experimental
Arm Description
11 patients belonging to this extension of Cohort 2A will be treated by EO2401 alone.
Arm Title
randomized extension of Cohort 2A (3 arms): C2A-III
Arm Type
Active Comparator
Arm Description
11 patients belonging to this extension of Cohort 2A who will be treated by nivolumab alone.
Intervention Type
Biological
Intervention Name(s)
EO2401
Intervention Description
Multiple dose of EO2401
Intervention Type
Biological
Intervention Name(s)
Nivolumab
Intervention Description
Multiple dose of nivolumab
Primary Outcome Measure Information:
Title
Adverse events assessment
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.
Time Frame
Up to 24 months
Secondary Outcome Measure Information:
Title
Evaluation of Progression Free Survival at 6 months
Description
Progression Free Survival according to iRECIST criteria defined as the time interval from the date of first study treatment administration to 6 months after
Time Frame
6 months after first treatment date from the last patient enrolled
Title
Evaluation of survival
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
Time Frame
From end of treatment to at least 24 months after last patient enrollment
Title
Assessment of the immunogenicity
Description
Assessment of the immunogenicity of the 4 components that compose EO2401 Immunogenicity will be assessed by Interferon-γ ELISpot
Time Frame
Up to 24 months

10. Eligibility

Sex
All
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Main Inclusion Criteria: For inclusion in Cohort 1 patients should have adrenocortical carcinoma(ACC), or malignant pheochromocytoma/paraganglioma (MPP), as defined below for Cohorts 2A and 3A. For inclusion in Cohorts 2A and 2B patients should have histologically confirmed (at primary diagnosis) unresectable locally advanced or metastatic adrenocortical carcinoma. 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. Patients with an age ≥ 18 years old. Patients who are human leukocyte antigen (HLA)-A2 positive. Patients with an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1. Patients with a life expectancy > 4 months as judged by their treating physician. Patients with at least one measurable lesion according to RECIST 1.1. Males or non-pregnant, non-lactating, females. Patients willing and able to comply with the scheduled visits, treatment plan, laboratory tests, and other study procedures indicated in the protocol. Patients having received the information sheet and who have provided written informed consent prior to any study-related procedures. Main Exclusion Criteria: 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. Patients with prior treatment with immune check-point inhibitors Patients with prior exposure to EO2401. 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. Patients with an initial diagnosis of ACC less than 9 months from start of screening part 2. Patients with ACC and any individual lesion according to RECIST 1.1 having a maximum diameter of more than 125 mm; irrespective if the lesion is proposed as a target lesion, or not, according to RECIST 1.1. Patients with ACC with more than three organs involved by disease, combined with unresectable primary tumor. Patients with ACC and uncontrolled hormonal secretion (according to the judgement of the treating physician). Patients with MPP and uncontrolled blood pressure (according to the judgement of the treating physician). Patients with abnormal laboratory values. Patients with persistent Grade 3 or 4 toxicities. Uncontrolled central nervous system (CNS) metastasis. Other malignancy or prior malignancy with a disease-free interval of less than 3 years Patients with clinically significant disease. Patients with suspected autoimmune or active autoimmune disorder or known history of an autoimmune neurologic condition (e.g. Guillain-Barré syndrome). Patients with history of solid organ transplantation or hematopoietic stem cell transplantation. Patients with history or known presence of tuberculosis. Pregnant and breastfeeding patients. Patients with history or presence of human immunodeficiency virus and/or potentially active hepatitis B virus/hepatitis C virus infection. 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. Patients with a history of hypersensitivity to any excipient present in the pharmaceutical forms of the study treatments. Patients treated with herbal remedies with immunostimulating properties or known to potentially interfere with major organ function. Patients with known ongoing drug and alcohol abuse. 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. Patients deprived of their liberty, under protective custody, or guardship.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jean-Michel Paillarse
Phone
+32 3 205 55 55
Email
medicalmonitoring@enterome.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jean-Michel Paillarse
Organizational Affiliation
Enterome
Official's Role
Study Director
Facility Information:
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vivek Subbiah, MD
Email
VSubbiah@mdanderson.org
First Name & Middle Initial & Last Name & Degree
Vivek Subbiah
Facility Name
Rigshospitalet
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kirsten Gedske Daugaard, MD
Email
kirsten.gedske.daugaard@regionh.dk
First Name & Middle Initial & Last Name & Degree
Kirsten Gedske Daugaard
Facility Name
Chu Lille
City
Lille
ZIP/Postal Code
59037
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christine Do Cao, MD
Email
christine.docao@chu-lille.fr
Facility Name
Centre Léon Bérard
City
Lyon
ZIP/Postal Code
69008
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christelle de la Fouchardière, MD
Email
christelle.delafouchardiere@lyon.unicancer.fr
First Name & Middle Initial & Last Name & Degree
Christelle de la Fouchardière
Facility Name
Assistance Publique - Hôpitaux de Marseille - Hôpital Nord
City
Marseille
ZIP/Postal Code
13915
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marie-Eve Garcia, MD
Email
marie-eve.garcia@ap-hm.fr
Facility Name
Institut Gustave Roussy
City
Villejuif
ZIP/Postal Code
94800
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eric Baudin, MD
Facility Name
Lmu Klinikum
City
München
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Matthias Kroiß, MD
Email
Matthias.Kroiss@med.uni-muenchen.de
First Name & Middle Initial & Last Name & Degree
Matthias Kroiß
Facility Name
Universitätsklinikum Würzburg
City
Würzburg
ZIP/Postal Code
97080
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Martin Fassnacht, MD
Facility Name
Azienda Ospedaliera Spedali Civili
City
Brescia
ZIP/Postal Code
25121
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Salvatore Grisanti, MD
Email
salvatore.grisanti@tin.it
First Name & Middle Initial & Last Name & Degree
Salvatore Grisanti
Facility Name
Amsterdam UMC, location VUmc
City
Amsterdam
ZIP/Postal Code
1081
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Catharina Willemien Menke - van der Houven van Oordt, MD
Email
c.menke@amsterdamumc.nl
First Name & Middle Initial & Last Name & Degree
Catharina Willemien Menke - van der Houven van Oordt
Facility Name
Hospital Universitari Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jaume Capdevilla, MD
Email
jcapdevila@vhio.net
First Name & Middle Initial & Last Name & Degree
Jaume Capdevila
Facility Name
Karolinska University Hospital
City
Stockholm
ZIP/Postal Code
17176
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dan Granberg, MD
Email
dan.granberg1954@icloud.com
First Name & Middle Initial & Last Name & Degree
Dan Granberg

12. IPD Sharing Statement

Plan to Share IPD
No

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

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