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