Phase IIb Clinical Trial With TGF-β2 Antisense Compound AP 12009 for Recurrent or Refractory High-grade Glioma

Isarna Therapeutics

Status and phase: Completed; Phase 2

Conditions: Glioblastoma; Anaplastic Astrocytoma

Treatments: Drug: temozolomide or PCV; Device: Drug delivery system for administration of AP 12009; Drug: AP 12009 10 µM; Drug: AP 12009 80 µM; Procedure: Placement of Drug Delivery System

Study type: Interventional

Funder types: Industry

Identifiers

NCT00431561

AP 12009-G004

Details and patient eligibility

About

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.

Full 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.

Enrollment: 141 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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141 participants in 3 patient groups

AP 12009 10 µM

Experimental group

Treatment:

Drug: AP 12009 10 µM

Device: Drug delivery system for administration of AP 12009

Procedure: Placement of Drug Delivery System

AP 12009 80 µM

Experimental group

Treatment:

Drug: AP 12009 80 µM

Device: Drug delivery system for administration of AP 12009

Procedure: Placement of Drug Delivery System

Chemotherapy

Active Comparator group

Treatment:

Drug: temozolomide or PCV