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Unable to recruit the projected patient number. All analyses are descriptive, only.
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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).
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.
Important note: Due to early trial termination, resulting in limited data availability, all analyses remain descriptive by nature, only. No conclusive endpoint analysis can be performed.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| trabedersen 10 µM | Experimental | 10 µM trabedersen (AP 12009), intratumoral infusion, every other week, 11 cycles, maximum 21 weeks |
|
| Chemotherapy | Active Comparator | temozolomide: capsules, up to 200 mg/sqm/day, 5 days per cycle, up to 26 cycles; carmustine: i.v. administration, up to 200 mg/sqm/day, 1 day per cycle, up to 8 cycles; 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| trabedersen | Drug |
|
| |
| temozolomide |
| Measure | Description | Time Frame |
|---|---|---|
| Survival Rate at 24 Months in the Intent-to-treat Population - Percentage of Participants (Descriptive Analysis, Only) | Survival rate was defined as the proportion of participants known to be alive at 24 months from randomization. If a participant's status was unknown and there was no follow-up information available, they were categorized as 'Died' for the purposes of the analysis. | 24 months |
| Survival at 24 Months in the Intent-to-treat Population - Number of Participants | Survival status was assessed at 24 months from randomization. Participants with unknown or missing status were considered treatment failures, i.e., assumed to be dead. The category "Lost to / insufficient follow-up" includes participants who were alive at last data collection point but did not yet have enough follow-up time to reach the 24 month time point. | 24 months |
| Measure | Description | Time Frame |
|---|---|---|
| Survival Rate at 12, 18, and 21 Months in the Intent-to-treat Population - Percentage of Participants (Descriptive Analysis, Only) | Survival rate was defined as the proportion of participants known to be alive at each time-point from randomization. Participants with unknown or missing status were considered treatment failures, i.e., assumed to be dead. | 12, 18, and 21 months |
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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:
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:
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.
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| Name | Affiliation | Role |
|---|---|---|
| Rolando Del Maestro, MD, PhD | Montreal Neurological Institute and Hospital | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| NJ Neuroscience Institute; JFK Medical Center | Edison | New Jersey | 08820 | United States | ||
| Winthrop University Hospital |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Randomization to First Dose |
|
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| Drug |
|
|
| Drug delivery system for administration of AP 12009 | Device | 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 | Procedure | Surgery for placement of intratumoral catheter and subcutaneous port access system as per routine clinical practice. Stereotactical catheter placement controlled by CT. |
|
| carmustine | Drug |
|
|
| lomustine | Drug |
|
|
| Survival at 12, 18, and 21 Months in the Intent-to-treat Population - Number of Participants | Survival status was assessed at each time-point from randomization. Participants with unknown or missing status were considered treatment failures, i.e., assumed to be dead. The category "Lost to follow-up" for each time-point includes participants who were alive at the last data collection point but did not yet have enough follow-up time to reach the time point. | 12, 18, and 21 months |
| Median Overall Survival (Days) From Randomization in the Intent-to-treat Population (Descriptive Analysis, Only) | Median overall survival was defined as the date of randomization to the date of death. If a participant's status was unknown and there was no follow-up information available, they were categorized as 'Died' for the purposes of the analysis. Analysis was by Kaplan-Meier estimation. | Up to 24 months |
| Response Category by Independent Review in the Intent-to-treat Population - Number of Participants | Tumor response was classified based on the (neuro-)radiologist's evaluation according to the Macdonald Response Criteria for bidimensionally measurable disease as outlined below:
Two qualified neuro-radiologists reviewed scans at each MRI time point, with adjudication of discrepancies by a third reviewer. Their findings and clinical information were independently reviewed by a neuro-oncologist, who made the assessment of overall response. | Up to 24 months |
| Overall Response Rate (CR+PR) by Independent Review in the Intent-to-treat Population - Percentage of Participants (Descriptive Analysis, Only) | Overall response rate was the proportion of participants with a best response of Complete Response (CR) or Partial Response (PR) observed from the start of treatment until disease progression. | Up to 24 months |
| Tumor Control Rate (CR+PR+SD) by Independent Review in the Intent-to-treat Population - Percentage of Participants (Descriptive Analysis, Only) | Tumor control rate was defined as the proportion of participants assessed as having Complete Response (CR), Partial Response (PR), or Stable Disease (SD). Participants with unknown or missing response were treated as non-responders. | Up to 24 months |
| Median Duration of Response (Days) by Independent Review (Descriptive Analysis, Only) | Duration of response was defined as the time from the first documentation of confirmed response (Complete Response, CR, or Partial Response, PR) to the first signs of Progressive Disease (PD), as assessed by the study neuro-oncologist. Median Duration of Response was calculated by Kaplan-Meier estimate. Censoring rules were:
| Up to 24 months |
| Disease Progression at 10, 12, 14, 16, 18, 21, and 24 Months by Independent Review in the Intent-to-treat Population - Number of Participants | Tumor response was classified based on the (neuro-)radiologist's evaluation:
Based on clinical and imaging data, an independent neuro-oncologist made the final assessment of "Progressed" versus "Not Progressed". Participants who had MRI assessment results missing or unknown were "UNK or missing", and were treated as "Progressed" for the purposes of the calculation. | 10, 12, 14, 16, 18, 21, and 24 months |
| 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) | Tumor response was classified based on the (neuro-)radiologist's evaluation:
Based on clinical and imaging data, an independent neuro-oncologist made the final assessment of "Progressed" versus "Not Progressed". Participants who had MRI assessment results missing or unknown were "UNK or missing", and were treated as "Progressed" for the purposes of the calculation. | 10, 12, 14, 16, 18, 21 and 24 months |
| Median Time to Progression (Days) by Independent Review for the Intent-to-treat Population (Descriptive Analysis, Only) | Time to progression was calculated from the date of randomization to the date of the first documented tumor progression. Participants who did not progress or died were censored at the last tumor assessment date or the date of start of a new anti-tumor treatment or death. | Up to 24 months |
| Mineola |
| New York |
| 11501 |
| United States |
| University of Rochester Medical Center | Rochester | New York | 14642 | United States |
| Hospital Británico | Buenos Aires | C1280AEB | Argentina |
| FLENI | Buenos Aires | C1428 | Argentina |
| Sanatorio Allende | Córdoba | X5000JHQ | Argentina |
| Universitätsklinik Innsbruck, Abteilung für Neurologie | Innsbruck | 6020 | Austria |
| AKH Wien, Klinik für Neurochirurgie | Vienna | 1090 | Austria |
| Hospital de Câncer de Barretos | Barretos / SP | 14784-400 | Brazil |
| Centro Goiano de Oncologia (CGO) | Goiânia | 74223-080 | Brazil |
| Hospital Sao Vicente de Paulo | Passo Fundo | 99010-080 | Brazil |
| Hospital de ClÃnicas de Porto Alegre | Porto Alegre | 90035-903 | Brazil |
| Hospital Sao Lucas da PUCRS | Porto Alegre | 90610-000 | Brazil |
| Hospital do Servidor Público Estadual | São Paulo | 04038-034 | Brazil |
| ECOGENE-21 Centre d'études cliniques | Chicoutimi | Quebec | G7H 7P2 | Canada |
| Foothills Medical Centre | Calgary | AB T2N 2T9 | Canada |
| Montreal Neurological Institute and Hospital | Montreal | H3A 2B4 | Canada |
| La Timone University Hospital | Marseille | 13385 | France |
| Klinik und Poliklinik für Neurochirurgie | Frankfurt/M. | 60528 | Germany |
| Universitätsklinikum Freiburg | Freiburg im Breisgau | 79106 | Germany |
| Neurochirurgische Klinik an der Universität Ulm am Bezirkskrankenhaus Günzburg | Günzburg | 89312 | Germany |
| Universitätklinikum Hamburg-Eppendorf, Klinik für Neurochirurgie | Hamburg | 20246 | Germany |
| Medizinische Hochschule Hannover Neurochirurgische Klinik | Hanover | 30625 | Germany |
| Universitätsklinik Heidelberg Neurologische Klinik | Heidelberg | 69120 | Germany |
| Universitätsklinikum Leipzig, Neurochirurgische Klinik | Leipzig | 04103 | Germany |
| Otto-von-Guericke-Universität, Klinik für Neurochirurgie | Magdeburg | 39120 | Germany |
| Klinik und Poliklinik für Neurochirurgie | Münster | 48149 | Germany |
| Klinik und Poliklinik für Neurologie | Regensburg | 93053 | Germany |
| Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ | Szeged | 6720 | Hungary |
| Manipal Hospital & Manipal Institute for Neurological Disorders | Bangalore | 560017 | India |
| NIMHANS | Bangalore | 560029 | India |
| BGS Global Hospital | Bangalore | 560060 | India |
| Postgraduate Institute of Medical Education & Research (PGIMER) | Chandigarh | 160012 | India |
| Apollo Speciality Hospitals | Chennai | 600006 | India |
| Care Hospitals | Hyderabaad | 500034 | India |
| Amrita Institute of Medical Sciences Research Center | Kochi | 560017 | India |
| AMRI Hospitals | Kolkata | 700029 | India |
| SGPGI of Medical Sciences | Lucknow | 226014 | India |
| Advanced Centre for Treatment Research and Education in Cancer (ACTREC) | Mumbai | 410210 | India |
| All India Institute of Medical Sciences (AIIMS) | New Delhi | 110029 | India |
| SCTIMST, Dept. of Neurosurgery | Thiruvananthapuram | 695011 | India |
| Hospital San Javier | Guadalajara | 44670 | Mexico |
| Hospital General de Mexico | Mexico City | 06120 | Mexico |
| Medica Sur | Mexico City | 14050 | Mexico |
| Wojskowy Szpital Kliniczny, Klinika Neurochirurgii | Bydgoszcz | 85-681 | Poland |
| Akademickie Centrum Kliniczne | Gdansk | 80-952 | Poland |
| SP ZOZ Uniwersytecki Szpital Kliniczny nr 1, Klinika Neurochirurgii | Lodz | 91-153 | Poland |
| Samodzielny Publiczny Szpital Kliniczny nr 4, Klinika Neurochirurgii i Neurochirurgii Dziecięcej | Lublin | 20-090 | Poland |
| Kliniczny Oddzial Neurochirurgii SUM w Sosnowcu Wojewódzki Szpital Specjalistyczny nr 5 | Sosnowiec | 41-200 | Poland |
| Centrum Onkologii - Instytut Im. Marii Sklodowskiej-Curie | Warsaw | 02-781 | Poland |
| Chelyabinsk City Hospital #3; Department of Neurosurgery | Chelyabinsk | 454021 | Russia |
| State Institution Russian Oncology Research Center N.N. Blokhin | Moscow | 115478 | Russia |
| Russian Scientific Research Neurosurgical Institute A.L. Polenov | Saint Petersburg | 191104 | Russia |
| Military Medical Academy, Neurosurgery Dept | Saint Petersburg | 194044 | Russia |
| Samara Region Clinical Hospital M.I. Kalinin | Samara | 443095 | Russia |
| Severance Hospital, Yonsei University College of Medicine | Seoul | 120-752 | South Korea |
| Kangnam St. Mary's Hospital | Seoul | 137-701 | South Korea |
| Asan Medical Center | Seoul | 138-736 | South Korea |
| Hospital de Cruces | Barakaldo | 48903 | Spain |
| Hospital Universitario Vall d'Hebron | Barcelona | 08035 | Spain |
| Hospital Doce de Octubre | Madrid | 28041 | Spain |
| Hospital Universitario Marqués de Valdecilla | Santander | 39008 | Spain |
| Hospital Universitario Virgen del RocÃo | Seville | 41013 | Spain |
| China Medical University Hospital | Taichung | 404 | Taiwan |
| Taichung Veterans General Hospital | Taichung | 407 | Taiwan |
| Tri-Service General Hospital | Taipei | 114 | Taiwan |
| Edinburgh Centre for Neuro-Oncology, Western General Hospital | Edinburgh | EH42XU | United Kingdom |
| The National Hospital for Neurology and Neurosurgery | London | WC1N 3BG | United Kingdom |
| FG001 | 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. |
| Catheter Surgery |
|
| First Dose of Study Drug / Chemotherapy |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
| First Dose to End of Study |
|
|
The Intent-to-treat population includes all participants randomized.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Number | participants |
| ||||||||||||||||
| Region of Enrollment | 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. | Number | participants |
| |||||||||||||||
| Height (cm) (Descriptive analysis, only) | Height is missing for one participant in the Chemotherapy group. | Mean | Standard Deviation | cm |
| ||||||||||||||
| Weight (kg) (Descriptive analysis, only) | Weight is missing for one participant in the Chemotherapy group. | Mean | Standard Deviation | kg |
| ||||||||||||||
| Diagnosis of Anaplastic Astrocytoma (AA) World Health Organization (WHO) Grade III | Twenty-six participants were diagnosed with Anaplastic Astrocytoma, and one participant was diagnosed with Secondary Glioblastoma Multiforme. | Number | participants |
| |||||||||||||||
| Time of first diagnosis of AA WHO Grade III (years) (Descriptive analysis, only) | 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. | Mean | Standard Deviation | years |
| ||||||||||||||
| Diagnosis of other brain tumor prior to diagnosis of Anaplastic Astrocytoma WHO Grade III | Twenty-six participants were diagnosed with Anaplastic Astrocytoma, and one participant was diagnosed with Secondary Glioblastoma Multiforme. | Number | participants |
| |||||||||||||||
| Diagnosis of Secondary Glioblastoma Multiforme (GBM) (WHO Grade IV) | Number | participants |
| ||||||||||||||||
| Time to first diagnosis of Secondary GBM (years) (Descriptive analysis, only) | 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). | Mean | Standard Deviation | years |
| ||||||||||||||
| Previous diagnosis of Astrocytoma or AA before diagnosis of Secondary Glioblastoma Multiforme | Number | participants |
| ||||||||||||||||
| One or more Prior Surgical Treatments | Number | participants |
| ||||||||||||||||
| One or more Prior Radiotherapy Regimens | Number | participants |
| ||||||||||||||||
| One or more Prior Chemotherapy | Number | participants |
| ||||||||||||||||
| One or more Prior Immunotherapy | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Survival Rate at 24 Months in the Intent-to-treat Population - Percentage of Participants (Descriptive Analysis, Only) | Survival rate was defined as the proportion of participants known to be alive at 24 months from randomization. If a participant's status was unknown and there was no follow-up information available, they were categorized as 'Died' for the purposes of the analysis. | The Intent-to-treat population includes all participants randomized. Early study discontinuation with site closures led to a high proportion of participants being censored or lost to follow-up in the initial analysis. Additional survival data were collected in a post-hoc fashion under a protocol amendment. These data are presented. | Posted | Number | 95% Confidence Interval | percentage of participants | 24 months |
|
|
| ||||||||||||||||||||||||||||
| Secondary | Survival Rate at 12, 18, and 21 Months in the Intent-to-treat Population - Percentage of Participants (Descriptive Analysis, Only) | Survival rate was defined as the proportion of participants known to be alive at each time-point from randomization. Participants with unknown or missing status were considered treatment failures, i.e., assumed to be dead. | The Intent-to-treat population includes all participants randomized. Early study discontinuation with site closures led to a high proportion of participants being censored or lost to follow-up in the initial analysis. Additional survival data were collected in a post-hoc fashion under a protocol amendment. These data are presented. | Posted | Number | 95% Confidence Interval | percentage of participants | 12, 18, and 21 months |
| ||||||||||||||||||||||||||||||
| Secondary | Survival at 12, 18, and 21 Months in the Intent-to-treat Population - Number of Participants | Survival status was assessed at each time-point from randomization. Participants with unknown or missing status were considered treatment failures, i.e., assumed to be dead. The category "Lost to follow-up" for each time-point includes participants who were alive at the last data collection point but did not yet have enough follow-up time to reach the time point. | The Intent-to-treat population includes all participants randomized. Early study discontinuation with site closures led to a high proportion of participants being censored or lost to follow-up in the initial analysis. Additional survival data were collected in a post-hoc fashion under a protocol amendment. These data are presented. | Posted | Number | participants | 12, 18, and 21 months |
| |||||||||||||||||||||||||||||||
| Secondary | Median Overall Survival (Days) From Randomization in the Intent-to-treat Population (Descriptive Analysis, Only) | Median overall survival was defined as the date of randomization to the date of death. If a participant's status was unknown and there was no follow-up information available, they were categorized as 'Died' for the purposes of the analysis. Analysis was by Kaplan-Meier estimation. | The Intent-to-treat population includes all participants randomized. Early study discontinuation with site closures led to a high proportion of participants being censored or lost to follow-up in the initial analysis. Additional survival data were collected in a post-hoc fashion under a protocol amendment. These data are presented. | Posted | Median | 95% Confidence Interval | days | Up to 24 months |
| ||||||||||||||||||||||||||||||
| Secondary | Response Category by Independent Review in the Intent-to-treat Population - Number of Participants | Tumor response was classified based on the (neuro-)radiologist's evaluation according to the Macdonald Response Criteria for bidimensionally measurable disease as outlined below:
Two qualified neuro-radiologists reviewed scans at each MRI time point, with adjudication of discrepancies by a third reviewer. Their findings and clinical information were independently reviewed by a neuro-oncologist, who made the assessment of overall response. | The Intent-to-treat population includes all participants randomized. | Posted | Number | participants | Up to 24 months |
| |||||||||||||||||||||||||||||||
| Secondary | Overall Response Rate (CR+PR) by Independent Review in the Intent-to-treat Population - Percentage of Participants (Descriptive Analysis, Only) | Overall response rate was the proportion of participants with a best response of Complete Response (CR) or Partial Response (PR) observed from the start of treatment until disease progression. | The Intent-to-treat population includes all participants randomized. | Posted | Number | 95% Confidence Interval | percentage of participants | Up to 24 months |
| ||||||||||||||||||||||||||||||
| Secondary | Tumor Control Rate (CR+PR+SD) by Independent Review in the Intent-to-treat Population - Percentage of Participants (Descriptive Analysis, Only) | Tumor control rate was defined as the proportion of participants assessed as having Complete Response (CR), Partial Response (PR), or Stable Disease (SD). Participants with unknown or missing response were treated as non-responders. | The Intent-to-treat population includes all participants randomized. | Posted | Number | 95% Confidence Interval | percentage of participants | Up to 24 months |
| ||||||||||||||||||||||||||||||
| Primary | Survival at 24 Months in the Intent-to-treat Population - Number of Participants | Survival status was assessed at 24 months from randomization. Participants with unknown or missing status were considered treatment failures, i.e., assumed to be dead. The category "Lost to / insufficient follow-up" includes participants who were alive at last data collection point but did not yet have enough follow-up time to reach the 24 month time point. | The Intent-to-treat population includes all participants randomized. Early study discontinuation with site closures led to a high proportion of participants being censored or lost to follow-up in the initial analysis. Additional survival data were collected in a post-hoc fashion under a protocol amendment. These data are presented. | Posted | Number | participants | 24 months |
| |||||||||||||||||||||||||||||||
| Secondary | Median Duration of Response (Days) by Independent Review (Descriptive Analysis, Only) | Duration of response was defined as the time from the first documentation of confirmed response (Complete Response, CR, or Partial Response, PR) to the first signs of Progressive Disease (PD), as assessed by the study neuro-oncologist. Median Duration of Response was calculated by Kaplan-Meier estimate. Censoring rules were:
| The Intent-to-treat population includes all participants randomized. | Posted | Median | 95% Confidence Interval | days | Up to 24 months |
| ||||||||||||||||||||||||||||||
| 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 | Tumor response was classified based on the (neuro-)radiologist's evaluation:
Based on clinical and imaging data, an independent neuro-oncologist made the final assessment of "Progressed" versus "Not Progressed". Participants who had MRI assessment results missing or unknown were "UNK or missing", and were treated as "Progressed" for the purposes of the calculation. | The Intent-to-treat population includes all participants randomized. | Posted | Number | participants | 10, 12, 14, 16, 18, 21, and 24 months |
| |||||||||||||||||||||||||||||||
| 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) | Tumor response was classified based on the (neuro-)radiologist's evaluation:
Based on clinical and imaging data, an independent neuro-oncologist made the final assessment of "Progressed" versus "Not Progressed". Participants who had MRI assessment results missing or unknown were "UNK or missing", and were treated as "Progressed" for the purposes of the calculation. | The Intent-to-treat population includes all participants randomized. | Posted | Number | 95% Confidence Interval | percentage of participants | 10, 12, 14, 16, 18, 21 and 24 months |
| ||||||||||||||||||||||||||||||
| Secondary | Median Time to Progression (Days) by Independent Review for the Intent-to-treat Population (Descriptive Analysis, Only) | Time to progression was calculated from the date of randomization to the date of the first documented tumor progression. Participants who did not progress or died were censored at the last tumor assessment date or the date of start of a new anti-tumor treatment or death. | The Intent-to-treat population includes all participants randomized. | Posted | Median | 95% Confidence Interval | days | Up to 24 months |
|
Safety monitoring (including adverse events) started from the signature of the informed consent and continued until 28 days after the last administration of study drug, up to 24 months.
Only treatment-emergent adverse events are listed, defined as any AE whose onset occurred or intensity worsened after undertaking the first study procedure or first dose of study drug (whichever occurred first) but less than 28 days after medication/procedures had stopped. Adverse events (including lab tests) were assessed at study visits.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. | 6 | 13 | 12 | 13 | ||
| EG001 | 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. | 0 | 11 | 9 | 11 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Grand mal convulsion | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Nervous system disorder | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Partial seizures | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Meningitis | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
| |
| Neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (13.0) | Systematic Assessment |
| |
| Pancytopenia | Blood and lymphatic system disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Haematemesis | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Device malfunction | General disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Device occlusion | General disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Neurosurgery | Surgical and medical procedures | MedDRA (13.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Partial seizures | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Brain oedema | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Hemiparesis | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Convulsion | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Epilepsy | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Facial palsy | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Grand mal convulsion | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Memory impairment | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Speech disorder | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Acquired epileptic aphasia | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Aphasia | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Burning sensation | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Complex partial seizures | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Hydrocephalus | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Hyperaesthesia | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Loss of consciousness | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Monoplegia | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Nervous system disorder | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Paralysis | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Simple partial seizures | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Chills | General disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Device occlusion | General disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Gait disturbance | General disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Administration site reaction | General disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Device alarm issue | General disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Device malfunction | General disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Medical device pain | General disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Medical device site reaction | General disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Pain | General disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Vessel puncture site haemorrhage | General disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Abdominal distention | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Abdominal tenderness | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Haematemesis | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA (13.0) | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA (13.0) | Systematic Assessment |
| |
| Neutrophil count | Investigations | MedDRA (13.0) | Systematic Assessment |
| |
| White blood cell count | Investigations | MedDRA (13.0) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (13.0) | Systematic Assessment |
| |
| CSF protein increased | Investigations | MedDRA (13.0) | Systematic Assessment |
| |
| Haemoglobin | Investigations | MedDRA (13.0) | Systematic Assessment |
| |
| Pseudomonas test positive | Investigations | MedDRA (13.0) | Systematic Assessment |
| |
| Staphylococcus test postivie | Investigations | MedDRA (13.0) | Systematic Assessment |
| |
| Weight increased | Investigations | MedDRA (13.0) | Systematic Assessment |
| |
| White blood cell count increased | Investigations | MedDRA (13.0) | Systematic Assessment |
| |
| Meningitis | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
| |
| Oral herpes | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
| |
| Skin bacterial infection | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Disorientation | Psychiatric disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Restlessness | Psychiatric disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Scar pain | Skin and subcutaneous tissue disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Acne | Skin and subcutaneous tissue disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Rash pruritic | Skin and subcutaneous tissue disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Incorrect dose administered | Injury, poisoning and procedural complications | MedDRA (13.0) | Systematic Assessment |
| |
| Meningitis chemical | Injury, poisoning and procedural complications | MedDRA (13.0) | Systematic Assessment |
| |
| Overdose | Injury, poisoning and procedural complications | MedDRA (13.0) | Systematic Assessment |
| |
| Blepharospasm | Eye disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Hippus | Eye disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (13.0) | Systematic Assessment |
| |
| Metastases to spine | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (13.0) | Systematic Assessment |
| |
| Urethral pain | Renal and urinary disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Urinary retention | Renal and urinary disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Varicose veins | Vascular disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Pancytopenia | Blood and lymphatic system disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Ear discomfort | Ear and labyrinth disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Neurosurgery | Surgical and medical procedures | MedDRA (13.0) | Systematic Assessment |
|
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.
Investigator and Sponsor both have publication / presentation privileges. Investigator abstracts or publications had to be reviewed and approved by the Sponsor prior to submission or presentation. The Clinic/Investigator agrees to delete information or defer publication or presentation, if (i) publication would hinder or delay the development of the investigational product or (ii) necessary to permit the filing of any desired patent applications by the Sponsor.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Officer | Isarna Therapeutics GmbH, formerly Antisense Pharma GmbH | +49-89-890831 | 0 | info@isarna-therapeutics.com |
| ID | Term |
|---|---|
| D001254 | Astrocytoma |
| D005909 | Glioblastoma |
| D009369 | Neoplasms |
| D001932 | Brain Neoplasms |
| D005910 | Glioma |
| ID | Term |
|---|---|
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
| D016543 | Central Nervous System Neoplasms |
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C525712 | Trabedersen |
| D000077204 | Temozolomide |
| D016503 | Drug Delivery Systems |
| D002330 | Carmustine |
| D008130 | Lomustine |
| ID | Term |
|---|---|
| D003606 | Dacarbazine |
| D014226 | Triazenes |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D004358 | Drug Therapy |
| D013812 | Therapeutics |
| D009607 | Nitrosourea Compounds |
| D014508 | Urea |
| D000577 | Amides |
| D009603 | Nitroso Compounds |
Not provided
Not provided
| Sponsor decision |
|
| Death |
|
| Lost to Follow-up |
|
| Male |
|
| Black |
|
| Asian |
|
| Hispanic or Latino |
|
| American Indian or Native Alaskan |
|
| Native Hawaiian or Other Pacific Islander |
|
| Austria |
|
| Russian Federation |
|
| India |
|
| Mexico |
|
| Canada |
|
| Germany |
|
| Israel |
|
| Poland |
|
| Recurrent |
|
| AA WHO Grade II |
|
| Not diagnosed with Other Brain Tumor |
|
| Other diagnosis |
|
| Previous diagnosis of Anaplastic Astrocytoma |
|
| No |
|
| No |
|
| No |
|
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.
|
|
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. |
|
|
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. |
|
|
| OG001 | 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. |
|
|
|
|
|
|
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. |
|
|
| OG001 | 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. |
|
|
| OG001 | 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. |
|
|
| OG001 | 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. |
|
|
|
|