Efficacy and Safety of AP 12009 in Patients With Recurrent or Refractory Anaplastic Astrocytoma or Secondary Glioblastoma

Exclusion Criteria

• •Patient unable or not willing to comply with the protocol regulations.
• •The investigator deems it necessary to surgically (re-)resect the present tumor (NOTE: the patient might still be eligible for randomization at a later timepoint).
• •Tumor surgery, tumor debulking, or other neurosurgery within 3 months prior to randomization. If a ≤48-hour routine post-surgery MRI (in accordance with study specifications) qualifies the patient for study participation, the patient can be randomized 30 ± 7 days post-surgery.
• •Radiotherapy or stereotactic (gamma knife) radiosurgery within 3 months prior to randomization.
• •Prior interstitial brachytherapy of the brain with permanent implants. Prior interstitial brachytherapy of the brain with removable implants within 3 months prior to randomization.
• •Chemotherapy, hormone therapy, or any other therapy with established or suggested anti-tumor effects within 4 weeks (nitrosoureas: 6 weeks) prior to randomization.
• •Prior anti-TGF-beta 2 targeted therapy.
• •Screening MRI shows a mass effect caused by the tumor defined as significant compression of the ventricular system and/or a midline shift (≥ 3 mm, central MRI review). Compression of the ventricular system and/or a midline shift ≥ 3 mm only due to the presence of (a) cyst(s) or scarring processes does not exclude an individual from the study.
• •Participation in another clinical study with another investigational medicinal product within 30 days prior to randomization.
• •History of a second independent malignant disorder within 5 years, except for carcinoma in situ of the cervix and basal cell carcinoma.
• •Presence of poorly controlled seizures.
• •Clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure, unstable angina, or poorly controlled arrhythmia. Myocardial infarction within 6 months prior to randomization.
• •Known HIV, HBV or HCV infection.
• •Acute viral, bacterial, or fungal infection.
• •Acute medical problems that may be considered to become an unacceptable risk, or any conditions, which might be contraindications for starting study treatment.
• •Presence of high risk for pulmonary toxicities, defined as:
• •1. Lung function: vital capacity ≤ 70%
• •2. Status following sequential or concomitant thoracic irradiation
• •3. Increased risk for a pulmonary toxicity induced by BCNU (Carmustine) or CCNU (Lomustine). Risk factors include smoking, presence of a respiratory condition, pre-existing radiographic pulmonary abnormalities, exposure to agents that cause lung damage.
• •History of allergies to reagents used in this study, history of celiac disease.
• •Drug abuse or extensive use of alcohol.
• •Clinically relevant psychiatric disorders / legal incapacity or a limited legal capacity.
• •Concomitant treatment with yellow fever vaccine.