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First-in-Human, Phase 1b/2a Trial of a Multipeptide Therapeutic Vaccine in Patients With Progressive Glioblastoma (ROSALIE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04116658
Recruitment Status : Not yet recruiting
First Posted : October 4, 2019
Last Update Posted : October 4, 2019
Sponsor:
Collaborator:
Covance
Information provided by (Responsible Party):
Enterome

Tracking Information
First Submitted Date  ICMJE September 30, 2019
First Posted Date  ICMJE October 4, 2019
Last Update Posted Date October 4, 2019
Estimated Study Start Date  ICMJE December 2019
Estimated Primary Completion Date January 31, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 3, 2019)
Safety and tolerability of EO2401: National Cancer Institute-Common Terminology Criteria for AEs (NCI-CTCAE) v5.0 [ Time Frame: Up to 24 months ]
Incidences of 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 Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: October 3, 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 of EO2316, EO2317, EO2318 (Three components of the therapeutic vaccine), and Universal Cancer Peptide that compose EO2401 [ Time Frame: Up to 24 months ]
    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 First-in-Human, Phase 1b/2a Trial of a Multipeptide Therapeutic Vaccine in Patients With Progressive Glioblastoma
Official Title  ICMJE A Multicenter, Open-Label, First-in-Human, Phase 1b/2a Trial of EO2401, a Novel Multipeptide Therapeutic Vaccine, With and Without Check Point Inhibitor, Following Standard Treatment in Patients With Progressive Glioblastoma
Brief Summary The purpose of this study is to assess the safety, tolerability, immunogenicity, and preliminary efficacy of EO2401 in patients with unequivocal evidence of progressive or first recurrent glioblastoma.
Detailed Description

This is a multicenter, Phase 1b/2a, First-In-Human study to assess the safety, tolerability, immunogenicity, and preliminary efficacy of EO2401 in patients with unequivocal evidence of progressive or first recurrent glioblastoma.

EO2401 is an innovative cancer peptide therapeutic vaccine based on the homologies between Tumor Associated Antigens and microbiome-derived peptides that will be administered alone and in combination with nivolumab, and nivolumab/bevacizumab to generate preliminary safety and efficacy data in patients with progressive glioblastoma.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Glioblastoma, Adult
Intervention  ICMJE Biological: Multiple dose of EO2401
Multiple dose administration of EO2401 coadministered with or without nivolumab (and bevacizumab, US only) during the priming phase
Study Arms  ICMJE
  • Experimental: Cohort 1
    Multiple dose of EO2041 monotherapy followed by continued EO2401 in combination with nivolumab
    Intervention: Biological: Multiple dose of EO2401
  • Experimental: Cohort 2
    Multiple dose of EO2041 in combination with nivolumab
    Intervention: Biological: Multiple dose of EO2401
  • Experimental: Cohort 3
    Multiple dose of EO2041 in combination with nivolumab and bevacizumab (US only)
    Intervention: Biological: Multiple dose of 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 Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: October 3, 2019)
32
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 31, 2023
Estimated Primary Completion Date January 31, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Patients with unequivocal documented (including histological confirmation of Glioblastoma-GB- at the primary diagnosis) evidence of progressive or first recurrent GB on MRI, as defined by RANO criteria
  2. Patients with at least 1 measurable lesion
  3. Patients with an age ≥ 18 years old
  4. Patients who are human leukocyte antigen (HLA)-A2 positive
  5. Patients with an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 or Karnofsky performance status ≥ 70
  6. Patients should have received standard therapy, including surgery (biopsy, incomplete or complete resection), radiation, temozolomide, if applicable

    1. Radiation therapy must have been finished 28 days before first study treatment administration
    2. Patients who received temozolomide as adjuvant therapy must have stopped the treatment and have a wash-out period of 28 days before first study treatment administration (6 weeks for nitrosoureas and 5 half lives for experimental therapies)
    3. Patients with unmethylated methylguanine-DNA-methyltransferase (MGMT) promoter can be included even if they have not received temozolomide prior to the inclusion in this clinical study)
  7. Female patients of childbearing potential must have a negative serum pregnancy test within 72 hours prior to dosing
  8. Considering the embryofetal toxicity of the nivolumab shown on animals' models, the following recommendations for contraception must be followed:

    a. If not surgically sterile, female patients of childbearing potential age must use highly effective barrier contraception from signing the Informed Consent Form (ICF) through 6 months after the last treatment dose administered. Highly effective barrier and non barrier contraception included: i. Combined (estrogen and progesterone containing) hormonal contraception associated with inhibition of ovulation: Oral Intravaginal Transdermal ii. Progestogen-only hormonal contraception associated with inhibition of ovulation: Oral Injectable Implantable iii. Intrauterine device iv. Intrauterine hormone-releasing system v. Bilateral tubal occlusion vi. Sexual abstinence. In each case of delayed menstrual period (over 1 month between menstruations), confirmation of absence of pregnancy is strongly recommended. This recommendation also applies to women of childbearing potential with infrequent or irregular menstrual cycles.

    b. If not surgically sterile, male with female partner of childbearing potential must use condom from signing the ICF through 8 months after the last treatment dose administered. Males must ensure that their partners of childbearing potential use highly effective barrier contraception also.

  9. Patients having received the information sheet and who have provided written informed consent prior to any study-related procedures
  10. Patients willing and able to comply with the scheduled visits, treatment plan, laboratory tests, and other study procedures indicated in the protocol.

Exclusion Criteria:

  1. Patients treated with dexamethasone > 2 mg/day or equivalent (i.e., 13 mg/day of prednisone) within 14 days before the first EO2401 administration, unless required to treat an adverse event (AE) Note: The criterion is applicable at the time of screening and also at the time of study treatment start (i.e. the patient should not have received treatment with dexamethasone > 2 mg/day or equivalent in the time between screening and study treatment start; this should be checked at the time of treatment start).
  2. Patients treated with PD (L)-1(Programmed-cell Death/Programmed-cell Death Ligand) immunotherapy, radiotherapy, and cytoreductive therapy within 28 days before the first EO2401 administration
  3. Patients with tumors primarily located in the infra-tentorial segment
  4. Patients with known radiological evidence of extracranial metastases
  5. Patients with presence of new hemorrhage (excluding, stable Grade 1) or uncontrolled seizure
  6. Patients with significant leptomeningeal disease
  7. Patients with abnormal (≥ Grade 2 National Cancer Institute-Common Terminology Criteria for AEs [NCI-CTCAE] version 5.0) laboratory values for hematology, liver, and renal function (serum creatinine). In detail, the following values apply as exclusion criteria:

    1. Hemoglobin < 10 g/dL (6.2 mmol/L)
    2. White blood cell count decrease (< 3.0 × 109/L) or increase (> 10.0 × 109/L)
    3. Absolute neutrophil count decrease (< 1.5 × 109/L)
    4. Platelet count decrease (< 75 × 109/L)
    5. Bilirubin > 1.5 × upper limit of normal (ULN; according to the performing laboratory's reference ranges)
    6. Alanine aminotransferase > 3 × ULN
    7. Aspartate aminotransferase > 3 × ULN
    8. Gamma-glutamyltransferase > 2.5 × ULN
    9. Serum creatinine increase (> 1.5 × ULN)
    10. Abnormal thyroid function: 0.3 > thyroid-stimulating hormone > 5 μU(μunit)/mL and 1.07 > free T3 > 3.37 nmol/L and 8.6 > free T4 > 25 pmol/L.
  8. For patients who are planned to receive bevacizumab:

    1. Patients with nephrotic syndrome
    2. Patients with proteinuria ≥ 2g/24 hours
    3. Patients with history or active gastrointestinal perforation and fistula
    4. Significant surgical procedure in the 4 weeks preceding the start of treatment or planned surgery
    5. Unhealed wound
    6. Patient with recent (4 weeks) history of hemoptysis of ½ teaspoon or more of red blood
    7. Thrombotic episode within 6 months
    8. Uncontrolled diabetes mellitus or hypertension
    9. Posterior reversible encephalopathy syndrome
  9. Patients with persistent Grade 3 or 4 toxicities (according to NCI-CTCAE v5.0). Toxicities must be resolved since at least 2 weeks to Grade 1 or less. However, alopecia or other persisting toxicities Grade ≤ 2 not constituting a safety risk based on Investigator's judgment is acceptable
  10. Patients with contraindication to contrast-enhanced MRI
  11. Other malignancy or prior malignancy with a disease-free interval of less than 3 years except those treated with surgical intervention and an expected low likelihood of recurrence such as basal cell or squamous cell skin cancer, or carcinoma in situ. Patients with adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ are eligible
  12. Patients with clinically significant cardiac disease, significant medical or psychiatric disease/condition that, in the opinion of the Investigator, would interfere with the evaluation of EO2401 or interpretation of patient safety or study results or that would prohibit the understanding or rendering of informed consent and compliance with the requirements of the protocol - including (but not limited to):

    1. New York Heart Association > Grade 2 congestive heart failure within 6 months prior to study entry
    2. Uncontrolled or significant cardiovascular disease, including:

    i. Myocardial infarction within 6 months prior to obtaining informed consent ii. Uncontrolled angina within 6 months prior to obtaining informed consent iii. Diagnosed or suspected congenital long QT syndrome iv. Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes) v. Unstable angina within 6 months prior to obtaining informed consent. c. Stroke within 6 months prior obtaining informed consent d. Concurrent neurodegenerative disease e. Dementia or significantly altered mental status.

  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 vitiligo, type I diabetes mellitus, hypothyroidism due to autoimmune condition only requiring hormone replacement therapy, psoriasis not requiring systemic therapy, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
  15. Patients with history of solid organ transplantation or hematopoietic stem cell transplantation
  16. Patients with history or known presence of tuberculosis
  17. Pregnant and breastfeeding patients
  18. Patients with history or presence of human immunodeficiency virus and/or hepatitis B virus/hepatitis C virus
  19. 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
  20. Patients with a history of hypersensitivity to any excipient present in the pharmaceutical form of investigational medicinal product
  21. Patients treated with herbal remedies with immunostimulating properties or known to potentially interfere with major organ function
  22. Patients with known drug and alcohol abuse
  23. 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
  24. Patients who have received treatment with any other investigational agent, or participation in another clinical trial within 28 days prior to enrollment and during the treatment period
  25. Patients deprived of their liberty or under protective custody or guardianship.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE France,   Germany,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04116658
Other Study ID Numbers  ICMJE EOGBM1-18
Has Data Monitoring Committee Not Provided
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 Not Provided
Responsible Party Enterome
Study Sponsor  ICMJE Enterome
Collaborators  ICMJE Covance
Investigators  ICMJE Not Provided
PRS Account Enterome
Verification Date October 2019

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