High grade malignant glioma
Conditions
Interventions
Product Name: 89Zr-GC1008
Product Code: n.a.
Pharmaceutical Form: Solution for injection
Product Name: GC1008
Product Code: GC1008
Pharmaceutical Form: Solution for infusion
Sponsors
University Medical Center Groningen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Part I 1. > 18 years 2. WHO 0,1,2 3. Patients with suspicion of malignant glioma on contrast-enhanced MRI within 4 weeks prior to enrolment. 4. Patients must be able to give written informed consent to participate. Patients may not be consented by a durable power of attorney. Part 2 Patients with relapsed malignant glioma Patient may have undergone surgery for the recurrence. If operated, residual and measurable disease after surgery is not required but surgery must have confirmed the recurrence. In case of operation, post-operative MRI must be made within 48 hours following surgery. Minimum interval of at least 4 weeks between surgery and the start of anti TGF betha treatment, and patients should have fully recovered from the surgery. For non operated patients, recurrent disease must be at least one bidimensionally measurable target lesion (contrast enhancing lesion) with one diameter of at least 2cm, based on MRI scan done within 4 weeks prior to start of treatment. 5. >18 years 6. WHO 0,1,2 7. Serum albumin =3.0 g/dL. 8. Adequate organ function including : a. Marrow: Hemoglobin =10.0 g/dL, absolute neutrophil count (ANC) =1,500/mm3, and platelets =100,000/mm3. b. Hepatic: Serum total bilirubin =1.5 x upper limit of normal (ULN) (Patients with Gilbert’s Disease may be included if their total bilirubin is =3.0 mg/dL), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) =2.5 x ULN. c. Renal: Estimated or measured creatinine clearance =60 mL/min. d. Other: Prothrombin time (PT) and partial thromboplastin time (PTT) within normal ranges. 9. Patients must have negative tests (antibody and/or antigen) for hepatitis viruses B and C and human immunodeficiency virus (HIV), unless the result is consistent with prior vaccination or prior infection with full recovery. 10. At the time of enrollment, patients must be >4 weeks since major surgery, radiotherapy, chemotherapy (=6 weeks if they were treated with a nitrosourea, mitomycin, or monoclonal antibodies such as bevacizumab), immunotherapy, or biotherapy/targeted therapies and recovered from the toxicity of prior treatment to = Grade 1, exclusive of alopecia. Concurrent cancer therapy is not permitted (except for corticosterioids) . (In patients who received long acting agents, a treatment free interval of 2 half lives should be considered.) 11. Patients must be able to give written informed consent to participate. Patients may not be consented by a durable power of attorney. 12. Male and female patients of child-producing potential must agree to use effective contraception while enrolled on study and receiving the experimental drug, and for at least 3 months after the last treatment. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 12
Exclusion criteria
Exclusion criteria: Part 1 1. Meningeal carcinomatosis, uncontrolled seizures, or a disease that either causes or threatens neurologic compromise (e.g., unstable vertebral metastases). 2. Pregnant or nursing women,: 3. A known allergy to any component of 89Zr-GC1008. 4. Patients who, in the opinion of the Investigator, have significant medical or psychosocial problems that warrant exclusion. Examples of significant problems include, but are not limited to: a. Other serious non-malignancy-associated medical conditions that may be significantly increase the risk of SAEs. b. Any condition, psychiatric, substance abuse, or otherwise, that, in the opinion of the Investigator, would preclude informed consent, consistent follow-up, or compliance Part 2: 5. History of ascites or pleural effusions , unless successfully treated, completely resolved, and the patient has not been treated for these conditions for >4 months. 6. Active thrombophlebitis, thromboembolism, hypercoagulability states, bleeding, or use of anti-coagulation therapy (including anti platelet agents such as aspirin, clopidogrel, ticlopidine, dipyridamole, and other agents used to induce long-acting platelet dysfunction). Patients with a history of deep venous thrombosis may participate if successfully treated, completely resolved, and no treatment has been given for >4 months. 7. Hypercalcemia: Calcium >11.0 mg/dL (2.75 mmol/L) unresponsive or uncontrolled in response to standard therapy (e.g., bisphosphonates). 8. Pregnant or nursing women, due to the unknown effects of GC1008 on the developing fetus or newborn infant. 9. Patients diagnosed with another malignancy – unless following curative intent therapy, the patient has been disease free for at least 5 years and the probability of recurrence of the prior malignancy is 38.1°C), or antibiotic therapy within 1 week prior to enrollment. 15. Systemic autoimmune disease (e.g., systemic lupus erythematosus, active rheumatoid arthritis, etc.). 16. A known allergy to any component of GC1008 or 89Zr-GC1008 . 17. Patients who, in the opinion of the Investigator, have significant medical or psychosocial problems that warrant exclusion. Examples of significant problems include, but are not limited to: a. Other serious non-malignancy-associated medical conditions that may be expected to limit life expectancy or significantly increase the risk of SAEs. b. Any condition, psychiatric
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part I: Feasibility of 89Zr-GC1008 PET imaging in patients with suspicion of a malignant glioma to assess if GC1008 penetrates into the brain tumor and to quantify its uptake. Part II: 89Zr-GC1008 PET imaging in patients with relapsed malignant glioma and phase II extension study with therapeutic GC1008 in relapsed malignant glioma patients ;Secondary Objective: Part I: Correlation of 89Zr-GC1008 tumor uptake with tumor histology, immuno-histochemistry for TGF-ß, VEGF expression, TGF-ß tumor levels as determined by ELISA. 89Zr-GC1008 biodistribution in humans. Part II: To evaluate tumor response as a preliminary assessment of clinical activity Correlation of 89Zr-GC1008 tumor uptake with treatment outcome (progression-free survival and overall survival). Correlation of 89Zr-GC1008 tumor uptake pre-surgery and at relapse in the subgroup that underwent a 89Zr-GC1008 PET scan before primary surgery ;Primary end point(s): Part 1: - Quantification of uptake of 89Zr-GC1008 as determined by PET imaging Part 2: Primary endpoint: - Quantification of uptake of 89Zr-GC1008 in relapsed malignant glioma patients as determined by PET imaging ;Timepoint(s) of evaluation of this end point: Part 1: after first 6 patients, at end of study Part 2: after first 6 patients, at end of study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part 1: - Correlation of 89Zr-GC1008 tumor uptake with tumor histology, immunohistochemistry for TGF-ß, VEGF expression, TGF-ß tumor levels as determined by ELISA. - 89Zr-GC1008 biodistribution in humans. Part 2: - Radiological Response Rate - Overall survival (OS) - 6-month progression-free survival (PFS) rate - Correlation of 89Zr-GC1008 tumor uptake with treatment outcome - Correlation of 89Zr-GC1008 tumor uptake pre-surgery and at relapse in the subgroup that underwent a 89Zr-GC1008 PET scan before primary surgery ;Timepoint(s) of evaluation of this end point: Part 1: after 12 patients, at end of study Part 2: after 12 patients, at end of study | — |
Countries
Netherlands
Contacts
Public ContactA.M.E. Walenkamp
UMCG
Outcome results
None listed