Anaplastic Astrocytoma, Glioblastoma
Conditions
Keywords
Glioblastoma, Anaplastic astrocytoma, Antisense, Cancer, Transforming growth factor beta2 (TGF-beta2), Targeted therapy, Immunotherapy, Brain tumor, Central nervous system (CNS), Convection-enhanced delivery (CED) / microperfusion, Locoregional application
Brief summary
In this multinational dose finding Phase IIb study the efficacy and safety of two doses of AP 12009 compared to standard chemotherapy (temozolomide or PCV) is investigated in adult patients with confirmed recurrent high-grade glioma.
Detailed description
The purpose of this study is to compare the safety and efficacy of two doses of AP 12009 and standard chemotherapy in adult patients with recurrent high-grade glioma (anaplastic astrocytoma \[AA\], WHO grade III; or glioblastoma \[GBM\], WHO grade IV). AP 12009 is a phosphorothioate antisense oligodeoxynucleotide specific for the mRNA of human transforming growth factor-beta2 (TGF-beta2). The growth factor TGF-beta plays a key role in malignant progression of various tumors by inducing proliferation, invasion, metastasis, angiogenesis and escape from immunosurveillance. It has been shown that in a number of tumor types the degree of TGF-beta production strongly correlates with tumor grade and stage. In patients with high-grade glioma, the TGF-beta2 overexpression is associated with disease stage, clinical prognosis and the immunodeficient state of the patients.
Interventions
DRUGAP 12009 10 µM
10 µM AP 12009 (trabedersen), intratumoral infusion, every other week, 11 cycles, maximum 21 weeks
DRUGAP 12009 80 µM
80 µM AP 12009 (trabedersen), intratumoral infusion, every other week, 11 cycles, maximum 21 weeks
DRUGtemozolomide or PCV
temozolomide: capsules, up to 200 mg/sqm/day, 5 days per cycle; PCV (procarbazine, CCNU, vincristine): standard regimen
Drug delivery system for Convection Enhanced Delivery consists of a portable pump with drug reservoir and infusion line. Main implanted parts are the port access system and the intratumoral catheter.
PROCEDUREPlacement of Drug Delivery System
Surgery for placement of intratumoral catheter and subcutaneous port access system as per routine clinical practice. Stereotactical catheter placement controlled by CT.
Sponsors
Isarna Therapeutics GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Histopathologically confirmed diagnosis of recurrent or refractory high-grade glioma (anaplastic astrocytoma, WHO grade III; or glioblastoma, WHO grade IV) * Supratentorial localization * No more than two chemotherapy regimens including radiochemotherapy since primary diagnosis * Eligible for either TMZ or PCV treatment * Recovery from acute toxicity caused by any previous therapy * Adequate organ functions * KPS at least 70%
Exclusion criteria
* Tumor surgery within 2 weeks prior to study entry * Radiation therapy within 8 weeks prior to study entry * Chemotherapy within 4 weeks prior to study entry (nitrosureas: 6 weeks) * No more than 3 mg/day dexamethasone (or equivalent) at baseline * Prior TGF-beta targeted therapy or tumor vaccination * Baseline MRI shows mass effect * Known active infection with HIV, HBV, or HCV; acute viral, bacterial, or fungal infection * Significant psychiatric disorders/legal incapacity or a limited legal capacity
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall response rate of two AP 12009 dose groups and control group assessed by the evaluation of tumor size on brain MRI scans | — |
Secondary
| Measure | Time frame |
|---|---|
| Response rates | at 3, 8, 10, and 12 months (and during the prolonged follow-up period in six-monthly intervals, if applicable) |
| Progression-free survival | six-month |
| Time to progression | — |
| Time to response | — |
| Overall survival | overall |
| Change of quality of life and Karnofsky Performance Status (KPS) | at 3, 8, 10, and 12 months (and during the prolonged follow-up period in six-monthly intervals, if applicable) |
| Best of all response rates | — |
| Safety and tolerability | — |
| Best of all response rates assessed by survival status and variation of tumor size on brain MRI | — |
Countries
Austria, Georgia, Germany, India, Israel, Russia
Outcome results
None listed