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)Therapeutic area: Diseases [C] - Cancer [C04]MedDRA version: 20.0 Level: PT Classification code 10018336 Term: Glioblastoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
- Registration Number
- EUCTR2018-002279-16-ES
- Lead Sponsor
- Enterome
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 32
1.Patients with unequivocal documented (including histological confirmation of 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
a.Radiation therapy must have been finished 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 28 days before first study treatment administration (6 weeks for nitrosoureas and 5 half lives for experimental therapies)
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)
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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
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 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).
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 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
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
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