Conditions: Anaplastic Astrocytoma Glioblastoma
Keywords: Anaplastic astrocytoma Glioblastoma Antisense Cancer Transforming Growth Factor beta 2 Targeted therapy Brain tumor Glioma Central Nervous System (CNS) Convection Enhanced Delivery (CED) Intratumoral administration
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 27
Healthy volunteers: no

Brief summary:
In this multinational Phase III study the efficacy and safety of 10 µM AP 12009 is compared to standard chemotherapy (temozolomide or BCNU or CCNU) in adult patients with confirmed recurrent or refractory anaplastic astrocytoma (WHO grade III) or secondary glioblastoma (WHO grade IV).

Detailed description:
The purpose of this study is to compare the safety and efficacy of the 10 µM concentration of AP 12009 and standard chemotherapy (temozolomide, BCNU, CCNU) in adult patients with recurrent or refractory anaplastic astrocytoma (AA, WHO grade III) or secondary glioblastoma (GBM, WHO grade IV). AP 12009 (trabedersen) is a phosphorothioate antisense oligodeoxynucleotide specific for the mRNA of human Transforming Growth Factor beta 2 (TGF-beta-2), which is applied intratumorally. 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. In patients with high-grade glioma, the TGF-beta-2 overexpression is associated with disease stage, clinical prognosis, and the immunodeficient state of the patients. Main objective of the study is to determine survival (rate) and tumor response.

Important note: Due to early trial termination, resulting in limited data availability, all analyses remain descriptive by nature, only. No conclusive endpoint analysis can be performed.

Arms:
arm 1: 10 µM trabedersen (AP 12009), intratumoral infusion, every other week, 11 cycles, maximum 21 weeks arm 2: temozolomide: capsules, up to 200 mg/sqm/day, 5 days per cycle, up to 26 cycles; carmustine: i.v. administration, up to 200 mg/sqm/day, 1 day per cycle, up to 8 cycles; lomustine: capsules, 110 mg/sqm/day, 1 day per cycle, up to 8 cycles. Only 1 of these 3 drugs/interventions is administered per patient in the comparator arm.

Interventions: intervention 1: trabedersen intervention 2: temozolomide intervention 3: Drug delivery system for administration of AP 12009 intervention 4: Placement of Drug Delivery System intervention 5: carmustine intervention 6: lomustine
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: Drug delivery system for Convection Enhanced Delivery consists of a portable pump (Pegasus vario or Pega vario) with drug reservoir (Pega Bag) and infusion line (Pega Line). Main implanted parts are the port access system (PORT-A-CATH) and the intratumoral catheter (Medtronic ventricular catheter). intervention 4: Surgery for placement of intratumoral catheter and subcutaneous port access system as per routine clinical practice. Stereotactical catheter placement controlled by CT. intervention 5: None intervention 6: None

Protocol document: