Efficacy and Safety of AP 12009 in Adult Patients with Recurrent or Refractory Anaplastic Astrocytoma (WHO grade III) as Compared to Standard Treatment with Temozolomide or BCNU: A Randomized, Actively Controlled, Open Label Clinical Phase III Study. - SAPPHIRE
- Conditions
- Recurrent or Refractory Anaplastic AstrocytomaMedDRA version: 9.1Level: LLTClassification code 10002224Term: Anaplastic astrocytoma
- Registration Number
- EUCTR2007-005802-38-FR
- Lead Sponsor
- Antisense Pharma GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 132
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 diagnosis of AA (WHO grade III) as confirmed by central histopathology.
4.The patient has a measurable lesion (> 2 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.The patient has recurrent or refractory disease, i.e. disease has progressed after:
a.Initial therapy with surgery and radiotherapy
b.Initial therapy with surgery and radiotherapy with concomitant chemotherapy
c.Initial therapy with surgery and radiotherapy with concomitant chemotherapy, followed by adjuvant chemotherapy
d.Initial therapy with surgery and radiotherapy, followed by chemotherapy
8.The patient has not received more than one chemotherapy regimen. 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.
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 10E9/L
f.WBC > 3 x 10E9/L
g.ANC > 1.5 x 10E9/L (or WBC > 3.0 x 10E9/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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
1.Patient unable or not willing to comply with the protocol regulations.
2.The patient is amenable to surgical resection of the tumor.
3.Tumor surgery, tumor debulking, or other neurosurgery within 30 days prior to randomization.
4.Radiotherapy or stereotactic (gamma knife) radiosurgery within 3 months prior to randomization.
5.Prior interstitial brachytherapy of the brain.
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 defined as significant impression of the ventricular system and/or a midline shift (=3 mm, central MRI review).
9.Participation in another clinical trial 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 occur frequently despite standard therapy for seizures, using drug doses, which result in maximum therapeutic drug plasma levels tolerated by the individual patient.
b.Seizures, which require frequent hospitalizations or other medical interventions because of their serial nature and/ or clinical symptoms.
c.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.Known 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). Risk factors include smoking, presence of a respiratory condition, pre-existing radiographic pulmonary abnormalities, exposure to agents that cause lung damage.
17.History of allergies to reagents used in this study.
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.
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Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method