Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
drksid header

  DRKS00003686

Trial Description

start of 1:1-Block title

Title

Efficacy and Safety of AP 12009 in Adult Patients With Recurrent or Refractory Anaplastic Astrocytoma or Secondary Glioblastoma as Compared to Standard Chemotherapy Treatment: A Randomized, Actively Controlled, Open Label Clinical Phase III Study.

end of 1:1-Block title
start of 1:1-Block acronym

Trial Acronym

SAPPHIRE

end of 1:1-Block acronym
start of 1:1-Block url

URL of the Trial

[---]*

end of 1:1-Block url
start of 1:1-Block public summary

Brief Summary in Lay Language

In this multinational Phase III study the efficacy and safety of 10 µM AP 12009 is compared
to standard chemotherapy (temozolomide or BCNU or CCNU) in adult patients with confirmed
recurrent or refractory anaplastic astrocytoma (WHO grade III) or secondary glioblastoma
(WHO grade IV).

end of 1:1-Block public summary
start of 1:1-Block scientific synopsis

Brief Summary in Scientific Language

The purpose of this study is to compare the safety and efficacy of the 10 µM concentration
of AP 12009 and standard chemotherapy (temozolomide, BCNU, CCNU) in adult patients with
recurrent or refractory anaplastic astrocytoma (AA, WHO grade III) or secondary glioblastoma
(GBM, WHO grade IV). AP 12009 (trabedersen) is a phosphorothioate antisense
oligodeoxynucleotide specific for the mRNA of human Transforming Growth Factor beta 2
(TGF-beta-2), which is applied intratumorally. 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. In patients with high-grade glioma, the
TGF-beta-2 overexpression is associated with disease stage, clinical prognosis, and the
immunodeficient state of the patients. Main objective of the study is to determine survival
(rate) and tumor response.

end of 1:1-Block scientific synopsis
start of 1:1-Block organizational data

Organizational Data

  •   DRKS00003686
  •   2012/05/15
  •   2008/09/26
  •   [---]*
  •   [---]*
  •   [---]*
end of 1:1-Block organizational data
start of 1:n-Block secondary IDs

Secondary IDs

  •   NCT00761280  (ClinicalTrials.gov)
  •   AP 12009-G005  (Antisense Pharma)
end of 1:n-Block secondary IDs
start of 1:N-Block indications

Health Condition or Problem studied

  •   Anaplastic Astrocytoma
  •   Glioblastoma
  •   C71 -  Malignant neoplasm of brain
end of 1:N-Block indications
start of 1:N-Block interventions

Interventions/Observational Groups

  •   Drug: trabedersen
  •   Drug: temozolomide
  •   Device: Drug delivery system for administration of AP 12009
  •   Procedure: Placement of Drug Delivery System
  •   Drug: carmustine
  •   Drug: lomustine
end of 1:N-Block interventions
start of 1:1-Block design

Characteristics

  •   Interventional
  •   [---]*
  •   Randomized controlled trial
  •   Open (masking not used)
  •   [---]*
  •   Active control (effective treament of control group)
  •   Treatment
  •   Parallel
  •   III
  •   [---]*
end of 1:1-Block design
start of 1:1-Block primary endpoint

Primary Outcome

- Survival rate; time frame: 24 months

end of 1:1-Block primary endpoint
start of 1:1-Block secondary endpoint

Secondary Outcome

- Progression rate; time frame: 10, 12, 14, 16, 18, 21, and 24 months
- Time to death (months)
- Overall response rate
- Tumor control rate
- Duration of response
- Time to progression (months)
- Survival rate; time frame: 12, 18, 21, 27, and 30 months; 3 and 4 years
- Quality of Life (EORTC QLQ-C30, Independent Living Score [ILS])

end of 1:1-Block secondary endpoint
start of 1:n-Block recruitment countries

Countries of Recruitment

  •   United States
  •   Argentina
  •   Austria
  •   Brazil
  •   Canada
  •   France
  •   Germany
  •   Hungary
  •   India
  •   Korea, Republic of
  •   Mexico
  •   Poland
  •   Russian Federation
  •   Spain
  •   Taiwan, Province of China
  •   United Kingdom
end of 1:n-Block recruitment countries
start of 1:n-Block recruitment locations

Locations of Recruitment

  •  
  •  
  •  
  •  
  •  
  •  
  •  
  •  
  •  
  •  
end of 1:n-Block recruitment locations
start of 1:1-Block recruitment

Recruitment

  •   [---]*
  •   2008/12/31
  •   180
  •   Multicenter trial
  •   International
end of 1:1-Block recruitment
start of 1:1-Block inclusion criteria

Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   70   Years
end of 1:1-Block inclusion criteria
start of 1:1-Block inclusion criteria add

Additional Inclusion Criteria

- The patient has provided written informed consent prior to any study-related
procedure.

- The patient is at least 18 years of age and equal to or below 70 years.

- The patient has a present diagnosis of AA or secondary GBM.

- The patient has a measurable lesion (> 1 ccm in volume, central MRI review).

- The lesion (or sum of lesions) does not exceed 50 ccm in volume (central MRI review).

- The tumor is localized supratentorially (central MRI review).

- 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. Secondary
GBM patients have progressed after a previous diagnosis of A and/or AA.

- The patient has not received more than one chemotherapy regimen. Radiation with
concomitant chemotherapy, followed by adjuvant chemotherapy, is considered as one
chemotherapy regimen.

- The patient is eligible for chemotherapy.

- 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.

- The patient is male or a non-pregnant, non-lactating female.

- 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.

- The patient must have recovered from acute toxicity caused by any previous therapy.

- The patient has a life expectancy of at least 3 months.

- The patient has a Karnofsky Performance Status of at least 70%.

- The patient shows adequate organ functions as assessed by the following screening
laboratory values:

1. Adequate renal function determined by serum creatinine and urea < 2 times the
upper limit of normal

2. Adequate liver function with ALT, AST and AP < 3 times the upper limit of
normal, and bilirubin < 2.5 mg/dL

3. INR < 1.5 and aPTT < 1.5 x ULN

4. Hemoglobin > 9 g/dL

5. Platelet count > 100 x 10E9/L

6. WBC > 3 x 10E9/L

7. ANC > 1.5 x 10E9/L (or WBC > 3.0 x 10E9/L)

end of 1:1-Block inclusion criteria add
start of 1:1-Block exclusion criteria

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.

end of 1:1-Block exclusion criteria
start of 1:n-Block addresses

Addresses

  • start of 1:1-Block address primary-sponsor
    • Isarna Therapeutics GmbH
    end of 1:1-Block address primary-sponsor
    start of 1:1-Block address contact primary-sponsor
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact primary-sponsor
  • start of 1:1-Block address scientific-contact
    • Montreal Neurological Institute and Hospital
    • Rolando Del Maestro, MD, PhD 
    end of 1:1-Block address scientific-contact
    start of 1:1-Block address contact scientific-contact
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact scientific-contact
  • start of 1:1-Block address public-contact
    • Montreal Neurological Institute and Hospital
    • Rolando Del Maestro, MD, PhD 
    end of 1:1-Block address public-contact
    start of 1:1-Block address contact public-contact
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact public-contact
end of 1:n-Block addresses
start of 1:n-Block material support

Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
    end of 1:1-Block address materialSupport
    start of 1:1-Block address contact materialSupport
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact materialSupport
end of 1:n-Block material support
start of 1:1-Block state

Status

  •   Recruiting stopped after recruiting started
  •   2012/06/01
end of 1:1-Block state
start of 1:n-Block publications

Trial Publications, Results and other Documents

  • [---]*
end of 1:n-Block publications
The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   8
  •   2013/10/30
* This entry means the parameter is not applicable or has not been set.