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

This study has been terminated.
(Unable to recruit the projected patient number. All analyses are descriptive, only.)
Sponsor:
Information provided by (Responsible Party):
Isarna Therapeutics GmbH
ClinicalTrials.gov Identifier:
NCT00761280
First received: September 26, 2008
Last updated: August 7, 2014
Last verified: August 2014
Results First Received: August 7, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Anaplastic Astrocytoma
Glioblastoma
Interventions: Drug: trabedersen
Drug: temozolomide
Device: Drug delivery system for administration of AP 12009
Procedure: Placement of Drug Delivery System
Drug: carmustine
Drug: lomustine

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Trabedersen 10 µM

10 µM trabedersen (AP 12009), intratumoral infusion, every other week, 11 cycles, maximum 21 weeks.

Drug delivery system for administration of AP 12009: Drug delivery system for Convection Enhanced Delivery consists of a portable pump (Pegasus vario or Pega vario) with drug reservoir (Pega Bag) and infusion line (Pega Line). Main implanted parts are the port access system (PORT-A-CATH) and the intratumoral catheter (Medtronic ventricular catheter).

Placement of Drug Delivery System: Surgery for placement of intratumoral catheter and subcutaneous port access system as per routine clinical practice. Stereotactical catheter placement controlled by CT.

Chemotherapy

Temozolomide: capsules, up to 200 mg/sqm/day, 5 days per cycle, up to 26 cycles.

OR carmustine: i.v. administration, up to 200 mg/sqm/day, 1 day per cycle, up to 8 cycles;

OR lomustine: capsules, 110 mg/sqm/day, 1 day per cycle, up to 8 cycles.

Only 1 of these 3 drugs/interventions is administered per patient in the comparator arm.


Participant Flow for 2 periods

Period 1:   Randomization to First Dose
    Trabedersen 10 µM     Chemotherapy  
STARTED     14     13  
Catheter Surgery     13 [1]   0 [2]
First Dose of Study Drug / Chemotherapy     12     11 [1]
COMPLETED     12     11  
NOT COMPLETED     2     2  
Withdrawal by Subject                 0                 2  
Sponsor decision                 1                 0  
Unknown                 1                 0  
[1] Safety population
[2] Not applicable to control group

Period 2:   First Dose to End of Study
    Trabedersen 10 µM     Chemotherapy  
STARTED     12     11  
COMPLETED     0 [1]   0 [1]
NOT COMPLETED     12     11  
End of trial                 5                 5  
Progressive disease                 5                 3  
Sponsor decision                 1                 2  
Death                 1                 0  
Lost to Follow-up                 0                 1  
[1] Study was discontinued early due to the inability to recruit a sufficient number of participants.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Intent-to-treat population includes all participants randomized.

Reporting Groups
  Description
Trabedersen 10 µM

10 µM trabedersen (AP 12009), intratumoral infusion, every other week, 11 cycles, maximum 21 weeks.

Drug delivery system for administration of AP 12009: Drug delivery system for Convection Enhanced Delivery consists of a portable pump (Pegasus vario or Pega vario) with drug reservoir (Pega Bag) and infusion line (Pega Line). Main implanted parts are the port access system (PORT-A-CATH) and the intratumoral catheter (Medtronic ventricular catheter).

Placement of Drug Delivery System: Surgery for placement of intratumoral catheter and subcutaneous port access system as per routine clinical practice. Stereotactical catheter placement controlled by CT.

Chemotherapy

Temozolomide: capsules, up to 200 mg/sqm/day, 5 days per cycle, up to 26 cycles.

OR carmustine: i.v. administration, up to 200 mg/sqm/day, 1 day per cycle, up to 8 cycles;

OR lomustine: capsules, 110 mg/sqm/day, 1 day per cycle, up to 8 cycles.

Only 1 of these 3 drugs/interventions is administered per patient in the comparator arm.

Total Total of all reporting groups

Baseline Measures
    Trabedersen 10 µM     Chemotherapy     Total  
Number of Participants  
[units: participants]
  14     13     27  
Age  
[units: years]
Mean ± Standard Deviation
  38.2  ± 12.72     40.8  ± 11.63     39.5  ± 12.05  
Gender  
[units: participants]
     
Female     5     5     10  
Male     9     8     17  
Race/Ethnicity, Customized  
[units: participants]
     
White     8     10     18  
Black     0     0     0  
Asian     6     2     8  
Hispanic or Latino     0     1     1  
American Indian or Native Alaskan     0     0     0  
Native Hawaiian or Other Pacific Islander     0     0     0  
Region of Enrollment [1]
[units: participants]
     
Spain     1     1     2  
Austria     0     1     1  
Russian Federation     4     4     8  
India     6     2     8  
Mexico     0     1     1  
Canada     0     1     1  
Germany     1     2     3  
Israel     0     1     1  
Poland     2     0     2  
Height (cm) (Descriptive analysis, only) [2]
[units: cm]
Mean ± Standard Deviation
  172.57  ± 9.913     170.29  ± 10.019     171.52  ± 9.829  
Weight (kg) (Descriptive analysis, only) [3]
[units: kg]
Mean ± Standard Deviation
  75.34  ± 17.265     71.62  ± 14.213     73.62  ± 15.731  
Diagnosis of Anaplastic Astrocytoma (AA) World Health Organization (WHO) Grade III [4]
[units: participants]
     
Refractory     3     2     5  
Recurrent     11     10     21  
Time of first diagnosis of AA WHO Grade III (years) (Descriptive analysis, only) [5]
[units: years]
Mean ± Standard Deviation
  1.71  ± 1.110     1.81  ± 1.194     1.75  ± 1.124  
Diagnosis of other brain tumor prior to diagnosis of Anaplastic Astrocytoma WHO Grade III [4]
[units: participants]
     
AA WHO Grade I     0     0     0  
AA WHO Grade II     1     0     1  
Not diagnosed with Other Brain Tumor     12     12     24  
Other diagnosis     1     0     1  
Diagnosis of Secondary Glioblastoma Multiforme (GBM) (WHO Grade IV)  
[units: participants]
  0     1     1  
Time to first diagnosis of Secondary GBM (years) (Descriptive analysis, only) [6]
[units: years]
Mean ± Standard Deviation
  NA  ± NA [8]   0.03  ± NA [7]   0.03  ± NA [7]
Previous diagnosis of Astrocytoma or AA before diagnosis of Secondary Glioblastoma Multiforme  
[units: participants]
     
Previous diagnosis of Astrocytoma     0     0     0  
Previous diagnosis of Anaplastic Astrocytoma     0     1     1  
One or more Prior Surgical Treatments  
[units: participants]
     
Yes     14     12     26  
No     0     1     1  
One or more Prior Radiotherapy Regimens  
[units: participants]
  14     13     27  
One or more Prior Chemotherapy  
[units: participants]
     
Yes     10     9     19  
No     4     4     8  
One or more Prior Immunotherapy  
[units: participants]
     
Yes     1     1     2  
No     13     12     25  
[1] Study was discontinued early because of the inability to recruit a sufficient number of suitable participants within the planned recruitment period, therefore not all planned sites recruited participants. Only those regions that recruited at least one participant are listed.
[2] Height is missing for one participant in the Chemotherapy group.
[3] Weight is missing for one participant in the Chemotherapy group.
[4] Twenty-six participants were diagnosed with Anaplastic Astrocytoma, and one participant was diagnosed with Secondary Glioblastoma Multiforme.
[5] Time of first diagnosis (in years before study entry) is available for all 14 participants in the Trabedersen group and 11 participants in the chemotherapy group.
[6] Time of first diagnosis (in years before study entry) of Secondary Glioblastoma Multiforme. One participant in the Chemotherapy group was diagnosed with Secondary Glioblastoma Multiforme (GBM); all other participants were diagnosed with Anaplastic Astrocytoma (AA).
[7] One participant in this group was diagnosed with Secondary Glioblastoma Multiforme.
[8] No participants in this group were diagnosed with Secondary Glioblastoma Multiforme.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Survival Rate at 24 Months in the Intent-to-treat Population - Percentage of Participants (Descriptive Analysis, Only)   [ Time Frame: 24 months ]

2.  Primary:   Survival at 24 Months in the Intent-to-treat Population - Number of Participants   [ Time Frame: 24 months ]

3.  Secondary:   Survival Rate at 12, 18, and 21 Months in the Intent-to-treat Population - Percentage of Participants (Descriptive Analysis, Only)   [ Time Frame: 12, 18, and 21 months ]

4.  Secondary:   Survival at 12, 18, and 21 Months in the Intent-to-treat Population - Number of Participants   [ Time Frame: 12, 18, and 21 months ]

5.  Secondary:   Median Overall Survival (Days) From Randomization in the Intent-to-treat Population (Descriptive Analysis, Only)   [ Time Frame: All follow-up ]

6.  Secondary:   Response Category by Independent Review in the Intent-to-treat Population - Number of Participants   [ Time Frame: All follow-up ]

7.  Secondary:   Overall Response Rate (CR+PR) by Independent Review in the Intent-to-treat Population - Percentage of Participants (Descriptive Analysis, Only)   [ Time Frame: All follow-up ]

8.  Secondary:   Tumor Control Rate (CR+PR+SD) by Independent Review in the Intent-to-treat Population - Percentage of Participants (Descriptive Analysis, Only)   [ Time Frame: All follow-up ]

9.  Secondary:   Median Duration of Response (Days) by Independent Review (Descriptive Analysis, Only)   [ Time Frame: All follow-up ]

10.  Secondary:   Disease Progression at 10, 12, 14, 16, 18, 21, and 24 Months by Independent Review in the Intent-to-treat Population - Number of Participants   [ Time Frame: 10, 12, 14, 16, 18, 21, and 24 months ]

11.  Secondary:   Disease Progression Rate at 10, 12, 14, 16, 18, 21, and 24 Months by Independent Review in the Intent-to-treat Population - Percentage of Participants (Descriptive Analysis, Only)   [ Time Frame: 10, 12, 14, 16, 18, 21 and 24 months ]

12.  Secondary:   Median Time to Progression (Days) by Independent Review for the Intent-to-treat Population (Descriptive Analysis, Only)   [ Time Frame: All follow-up ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Early termination of the study leading to recruitment of 27 of 180 planned subjects and incomplete collection of data. Survival results are based on post-study collection of additional survival data under a protocol amendment.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Medical Officer
Organization: Isarna Therapeutics GmbH, formerly Antisense Pharma GmbH
phone: +49-89-890831 ext 0
e-mail: info@isarna-therapeutics.com


No publications provided


Responsible Party: Isarna Therapeutics GmbH
ClinicalTrials.gov Identifier: NCT00761280     History of Changes
Other Study ID Numbers: AP 12009-G005
Study First Received: September 26, 2008
Results First Received: August 7, 2014
Last Updated: August 7, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Austria: Federal Office for Safety in Health Care
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Israel: Ethics Commission
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Spain: Spanish Agency of Medicines
Russia: Ministry of Health of the Russian Federation
United Kingdom: Medicines and Healthcare Products Regulatory Agency
India: Drugs Controller General of India
Mexico: Federal Commission for Sanitary Risks Protection
Brazil: National Health Surveillance Agency
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Hungary: National Institute of Pharmacy
South Korea: Korea Food and Drug Administration (KFDA)
Taiwan : Food and Drug Administration