A First-in-Human, Early Phase Trial to investigate EO2401, a Novel Cancer Vaccine Therapy, with and without an Immune-Checkpoint Blocker, Following Standard Treatment in Patients with Progressive or Recurrent Glioblastoma Multiforme, a Certain Form of Brain Cancer
- Conditions
- Progressive or recurrent Glioblastoma (PG)MedDRA version: 20.0Level: PTClassification code 10018336Term: GlioblastomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-002279-16-DE
- Lead Sponsor
- Enterome
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 100
1.Patients with unequivocal documented (including histological confirmation of GB at the primary diagnosis) first progression/recurrence of GB on MRI, as defined by RANO criteria
2.Patients with:
• for Cohorts1, 2a, and 3: at least 1 measurable lesion
• for Cohort 2b: no measurable enhancing disease (defined as less than 1x1 cm in maximum bi-perpendicular plane)
• for Cohort 2c: documented recurrence of GB deemed to be candidate for surgery as standard-of-care at the local institution, and for which the resection can safely be postponed for 4-6 weeks per local institutional guidance and treating physician judgement. In addition, for inclusion in Cohort 2c the patient must consent to mandatory collection of tissue samples from the time of diagnosis (if logistically available), and the planned surgery after neoadjuvant study therapy (see also Section 7.1.1).
3. Patients
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 primary therapy, including surgery (biopsy, incomplete or complete resection), radiation, temozolomide, if applicable
a.Radiation therapy must have been finished at least 28 days before first study treatment administration
b.Patients who received temozolomide as adjuvant therapy must have stopped the treatment and have a wash-out period of at least 28 days before first study treatment administration (6 weeks for nitrosoureas and at least 4 weeks, or 5 half-lives if longer, for experimental therapies, if this type of therapies have been included as components of adjuvant therapy)
c .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). Note, patients to be enrolled to the trial at sites in Germany should have received temozolomide for their primary treatment irrespective of MGMT methylation status; i.e. both concurrent with radiotherapy and as adjuvant therapy post radiotherapy, when applicable as standard therapy.
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 contraception from signing the Informed Consent Form (ICF) through 6 months after the last treatment dose administered. Highly effective 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
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)
2.Patients treated with radiotherapy, and cytoreductive therapy within 28 days (6 weeks for nitrosoureas) before the first EO2401 administration. In addition, patients should not have received any prior treatment with compounds targeting PD-1, PD-L1, CTLA-4, or similar compounds where general resistance against therapeutic vaccination approaches might have developed; also patients should not have received systemic anti-Tumor treatment or radiotherapy for their progressive or first recurrent GB
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).
8.For patients who are planned to receive bevacizumab:
a.Patients with nephrotic syndrome
b.Patients with proteinuria = 2g/24 hours
c.Patients with history or active gastrointestinal perforation and fistula
d.Significant surgical procedure in the 4 weeks preceding the start of treatment or planned surgery
e.Unhealed wound
f.Patient with recent (4 weeks) history of hemoptysis of ½ teaspoon or more of red blood
g.Thrombotic episode within 6 months
h.Uncontrolled diabetes mellitus or hypertension
i.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 active infection, 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 (i.e. only consent able patients can be enrolled in the study) and compliance with the requirements of the protocol
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
18.Patients who have received live or attenuated vaccine therapy used for prevent
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method