Evaluation of efficacy and safety of the new drug AP 12009 in adult patients suffering from Recurrent or Refractory Anaplastic Astrocytoma (WHO grade III) or Secondary Glioblastoma (WHO grade IV) compared to standard treatment with Temozolomide or Lomustine: A clinical study where patients will be openly and randomly assigned to one of the treatment groups to gain marketing approval for the new drug AP 12009.

Conditions: Recurrent or Refractory Anaplastic Astrocytoma (WHO grade III) or secondary Glioblastoma (WHO grade IV)
MedDRA version: 14.0Level: PTClassification code 10018336Term: GlioblastomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]
MedDRA version: 14.0Level: PTClassification code 10002224Term: Anaplastic astrocytomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Registration Number: EUCTR2007-005802-38-DE

Lead Sponsor: Antisense Pharma GmbH

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 180

Inclusion Criteria

1. The patient has provided written informed consent prior to any study-related procedure.
2. The patient is at least 18 years of age and equal to or below 70 years.
3. The patient has a present diagnosis of AA or secondary GBM.
4. The patient has a measurable lesion (> 1 cm3 in volume, central MRI review).
5. The lesion (or sum of lesions) does not exceed 50 cm3 in volume (central MRI review).
6. The tumor is localized supratentorially (central MRI review).
7. All patients have recurrent or refractory disease, i.e. disease has progressed after:
Prior surgery and radiotherapy at any time of the disease course or stage (e.g. prior grade II tumor).
Secondary GBM patients have progressed after a previous diagnosis of A and/or AA.
In case of recent tumor surgery a = 48-hour routine post-surgery MRI (in accordance with study specifications) confirming inclusion criteria 4, 5, and 6 qualifies the patient for study randomization 30 ± 7 days after surgery.
8. The patient has not received more than 2 chemotherapy regimens. Radiation with concomitant
chemotherapy, followed by adjuvant chemotherapy, is considered as one chemotherapy regimen.
9. The patient is eligible for chemotherapy.
10. The patient is on a maximum dose of 4 mg/day dexamethasone or equivalent doses for other corticosteroids, which has been stable or decreasing for at least 3 weeks prior to Screening.
11. The patient is male or a non-pregnant, non-lactating female.
12. Females of childbearing potential must have a negative beta-HCG pregnancy test at Screening. Females of childbearing potential and males must practice strict birth control (see Section 8.2).
13. The patient must have recovered from acute toxicity caused by any previous therapy.
14. The patient has a life expectancy of at least 3 months.
15. The patient has a Karnofsky Performance Status of at least 70%.
16. The patient shows adequate organ functions as assessed by the following screening laboratory values:
a. Adequate renal function determined by serum creatinine and urea < 2 times the upper limit of normal
b. Adequate liver function with ALT, AST and AP < 3 times the upper limit of normal, and bilirubin < 2.5 mg/dL
c. INR < 1.5 and aPTT < 1.5 x ULN
d. Hemoglobin > 9 g/dL
e. Platelet count > 100 x 1 000 000 000/L
f. WBC > 3 x 1 000 000 000/L
g. ANC > 1.5 x 1 000 000 000/L (or WBC > 3.0 x 1 000 000 000/L)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 117
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 63

Exclusion Criteria

1. Patient unable or not willing to comply with the protocol regulations.
2. 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, see inclusion criterion 7 and exclusion criterion 3).
3. 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 (see inclusion criterion 7), the patient can be randomized 30 ± 7 days post-surgery.
4. Radiotherapy or stereotactic (gamma knife) radiosurgery within 3 months prior to randomization.
5. Prior interstitial brachytherapy of the brain with permanent implants. Prior interstitial brachytherapy of the brain with removable implants within 3 months prior to randomization.
6. Chemotherapy, hormone therapy, or any other therapy with established or suggested anti-tumor effects within 4 weeks (nitrosoureas: 6 weeks) prior to randomization.
7. Prior anti-TGF-beta 2 targeted therapy.
8. 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.
9. Participation in another clinical study with another investigational medicinal product within 30 days prior to randomization.
10. History of a second independent malignant disorder within 5 years, except for carcinoma in situ of the cervix and basal cell carcinoma.
11. Presence of poorly controlled seizures, defined as:
a. Seizures, which require frequent hospitalizations or other medical interventions because of their serial nature and/or clinical symptoms.
b. Seizure symptoms, which significantly interfere with normal life and restrict medical treatments that are necessary for patient care.
12. 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.
13. HIV, HBV or HCV infection.
14. Acute viral, bacterial, or fungal infection.
15. Acute medical problems that may be considered to become an unacceptable risk, or any conditions, which might be contraindications for starting study treatment.
16.Presence of high risk for pulmonary toxicities, defined as:
a. Lung function: vital capacity = 70%
b. Status following sequential or concomitant thoracic irradiation
c. 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.18. Drug abuse or extensive use of alcohol.
17. History of allergies to reagents used in this study, history of coeliac disease (gluten intolerance).
18. Drug abuse or extensive use of alcohol.
19. Clinically relevant psychiatric disorders/legal incapacity or a limited legal capacity.
20. Concomitant treatment with yellow fever vaccine.