An open-label, Phase I/II multicenter clinical trial of VXM01 in combination with avelumab in patients with progressive glioblastoma following standard treatment, with or without second surgery.
- Conditions
- Glioblastomabrain tumour
- Registration Number
- NL-OMON48738
- Lead Sponsor
- VAXIMM GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 9
1. Subjects who are able to understand and follow instructions during the trial
2. Ability and willingness to give written informed consent, signed and dated
3. Male or female subjects. Female subjects must be post-menopausal for at
least 2 years or surgically sterile
4. Age >=18 years
5. Histologically diagnosed intracranial supratentorial malignant glioma
(contrast-enhancing glioblastoma WHO Grade IV)
6. Evidence of tumor progression by RANO criteria following at least one prior
therapy regimen that must have contained radiation and chemotherapy with
temozolomide, as measured by MRI
* Radiotherapy must have been completed at least 3 months prior to the
inclusion visit
7. Candidates for a tumor reoperation (for the resectable arm [n=6] only)
* Neurosurgical intervention should be postponable for 30 days
8. Adequate bone marrow function including: Absolute neutrophil count (ANC)
>=1,500/mm3 or >=1.5 x 10^9/L; Platelets >= 100,000/mm3 or >=100 x 10^9/L;
Hemoglobin >= 9 g/dL (may have been transfused); INR <1.5x ULN. Subjects with
documented benign cyclical neutropenia are allowed if WBC count is >= 1.5 ×
10^9/L with absolute neutrophil count >= 1.0 × 10^9/L and appropriate hematology
parameters: leukocytes >=4.0 x 10^9 / L, lymphocytes >=0.6 x 10^9/L
9. Adequate hepatic function defined by a total bilirubin level <= 1.5 × the
upper limit of normal range (ULN), an aspartate aminotransferase (AST), level <=
2.5 × ULN, and an alanine aminotransferase (ALT) level <= 2.5 × ULN or, for
subjects with documented metastatic disease to the liver, AST and ALT levels <=
5 × ULN. Subjects with documented Gilbert disease are allowed if total
bilirubin <= 3 x ULN
10. Adequate renal function defined by an estimated creatinine clearance >= 30
mL/min according to the Cockcroft-Gault formula
11. Patients must be able to undergo MRI
12. Absence of active bacterial infection requiring antibiotic treatment
13. Karnofsky performance status >=70
14. Primary (or most recently obtained available) tumor samples available for
pathology review, panel sequencing, as well as central detection of T-cell
responses in the peripheral blood and in the tumor tissue
15. No medical or social conditions that may interfere with trial outcome and
follow-up
1. Cardiovascular disease defined as:
a. Uncontrolled hypertension (systolic blood pressure >160 mmHg or diastolic
blood pressure >100 mmHg)
b. Arterial thromboembolic event within 6 months before trial entry including:
* Myocardial infarction
* Unstable angina pectoris
* Cerebrovascular accident
* Transient ischemic attack
2. Congestive heart failure New York Heart Association grade III to IV
3. Serious ventricular arrhythmia requiring medication and arrhythmias
requiring Implantable Cardioverter Defibrillator (ICDs)
4. Clinically significant peripheral artery disease > grade 2b according to
Fontaine
5. History of relevant intracranial hemorrhage (not confined to susceptibility
(iron) lesions on MRI only)
6. Hemoptysis within 6 months before trial entry
7. Known oesophageal varices
8. Upper or lower gastrointestinal bleeding within 6 months before inclusion
(Day 0)
9. Significant traumatic injury or surgery within 4 weeks before trial entry
10. Non-healing wound, incomplete wound healing, bone fracture or
gastrointestinal ulcers within three years before inclusion, or positive
gastroscopy within 3 months before inclusion
11. Gastrointestinal fistula
12. Thrombolysis therapy within 4 weeks before trial entry
13. History of other disease, metabolic dysfunction, physical examination
finding, or clinical laboratory finding that based on the investigators
judgement provides a reasonable suspicion of a disease or condition that
contraindicates the use of an investigational drug or that might affect the
interpretation of the trial results or render the patient at high risk for
treatment complications
14. Previous malignant disease (other than the tumor disease for this trial)
within the last 5 years (except adequately treated non-melanoma skin cancers,
carcinoma in situ of skin, bladder, cervix, colon/rectum, breast, or prostate)
unless a complete remission without further recurrence was achieved at least 2
years prior to trial entry and the subject was deemed to have been cured with
no additional therapy required or anticipated to be required
15. Prior organ transplantation, including allogeneic stem cell transplantation
16. Active autoimmune disease that might deteriorate when receiving an
immunostimulatory agent:
a. Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid
disease not requiring immunosuppressive treatment are eligible
b. Administration of steroids through a route known to result in a minimal
systemic exposure (topical, intranasal, intro-ocular, or inhalation) are
acceptable
17. History of uncontrolled intercurrent illness including but not limited to
uncontrolled diabetes (e.g., hemoglobin A1c >= 8%)
18. Known prior hypersensitivity to investigational product or any component in
its formulations or any other drug scheduled or likely to be given during the
trial, including known severe hypersensitivity reactions to monoclonal
antibodies (NCI CTCAE v5.0 Grade >= 3)
19. Persisting toxicity related to prior therapy (NCI CTCAE v5.0 Grade > 1);
however, alopecia, sensory neuropathy Grade <= 2, or other Grade <= 2 AEs not
constituting a safety risk based on investigator*s judgment are acceptable
20. Other severe acute or chronic medical conditions including immune colitis,
inflammatory bowel diseas
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Endpoint:<br /><br>• Safety and tolerability up to 60 weeks after first IMP administration (incl.<br /><br>EoS visit, week 60)</p><br>
- Secondary Outcome Measures
Name Time Method