An early phase clinical study of VXM01 in combination with avelumab in patients with brain cancer following standard treatment.
- Conditions
- Progressive glioblastoma (WHO grade IV)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
- EUCTR2017-003076-31-DE
- Lead Sponsor
- VAXIMM GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 30
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
?Raditotherapy 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 109/L; Platelets = 100,000/mm3 or =100 x 109/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 × 109/L with absolute neutrophil count = 1.0 × 109/L and appropriate hematology parameters: leukocytes =4.0 x 109 / L, lymphocytes =0.6 x 109/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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15
1.Cardiovascular disease:
- uncontrolled hypertension
- arterial thromboembolic event within 6 m before trial entry
2.Congestive heart failure NY Heart Association grade III to IV
3.Serious ventricular arrhythmia requiring medication and arrhythmias requiring ICD
4.Clinically significant peripheral artery disease > grade 2b according to Fontaine
5.History of relevant intracranial hemorrhage
6.Hemoptysis within 6 m before trial entry
7.Known oesophageal varices
8.Upper or lower gastrointestinal bleeding within 6 m before inclusion
9.Significant traumatic injury or surgery within 4 w 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 m before inclusion
11.Gastrointestinal fistula
12.Thrombolysis therapy within 4 w 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 glioblastoma) within the last 5 y (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 are acceptable
17.History of uncontrolled intercurrent illness including but not limited to uncontrolled diabetes
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 to monoclonal antibodies (Grade = 3)
19.Persisting toxicity related to prior therapy (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 disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with trial participation or trial treatment administration or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the patient inappropriate for entry into this trial
21.Active infection requiring systemic therapy
22.Known history of HIV or known acquired immunodeficiency syndrome or multi-drug resistant gram-negative bacteria
23.HBV or HCV infection at screening
24.Women of childbearing potential
25.History of serious ophthalmologic
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