Anaplastic AstrocytomaPhase 3SAPPHIRENCT00761280
Efficacy and Safety of AP 12009 in Patients With Recurrent or Refractory Anaplastic Astrocytoma or Secondary Glioblastoma
A Phase 3 study testing trabedersen, temozolomide and Drug delivery system for administration of AP 12009 in people with Anaplastic Astrocytoma and Glioblastoma, run by Isarna Therapeutics GmbH at 68 sites in 16 countries.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Anaplastic Astrocytoma, Glioblastoma
- What is being tested?
- trabedersen, temozolomide and Drug delivery system for administration of AP 12009
- Type of treatment
- Pill or oral medicine, Injection or infusion, Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 68 sitesin 16 countries
- Study dates
- Dec 2008to Jun 2012
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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:
- Adequate renal function determined by serum creatinine and urea < 2 times the upper limit of normal
- Adequate liver function with ALT, AST and AP < 3 times the upper limit of normal, and bilirubin < 2.5 mg/dL
- INR < 1.5 and aPTT < 1.5 x ULN
- Hemoglobin > 9 g/dL
- Platelet count > 100 x 10E9/L
- WBC > 3 x 10E9/L
- ANC > 1.5 x 10E9/L (or WBC > 3.0 x 10E9/L)
Who cannot join
- 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.
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- 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:
- Lung function: vital capacity ≤ 70%
- Status following sequential or concomitant thoracic irradiation
- 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.
Trial locations and contacts
68 sites in 16 countries.
68 sites in 16 countries
India12 sites
Manipal Hospital & Manipal Institute for Neurological Disorders
Bangalore, 560017
NIMHANS
Bangalore, 560029
BGS Global Hospital
Bangalore, 560060
Postgraduate Institute of Medical Education & Research (PGIMER)
Chandigarh, 160012
Apollo Speciality Hospitals
Chennai, 600006
Care Hospitals
Hyderabaad, 500034
Amrita Institute of Medical Sciences Research Center
Kochi, 560017
AMRI Hospitals
Kolkata, 700029
SGPGI of Medical Sciences
Lucknow, 226014
Advanced Centre for Treatment Research and Education in Cancer (ACTREC)
Mumbai, 410210
All India Institute of Medical Sciences (AIIMS)
New Delhi, 110029
SCTIMST, Dept. of Neurosurgery
Thiruvananthapuram, 695011
Germany10 sites
Klinik und Poliklinik für Neurochirurgie
Frankfurt/M., 60528
Universitätsklinikum Freiburg
Freiburg im Breisgau, 79106
Neurochirurgische Klinik an der Universität Ulm am Bezirkskrankenhaus Günzburg
Günzburg, 89312
Universitätklinikum Hamburg-Eppendorf, Klinik für Neurochirurgie
Hamburg, 20246
Medizinische Hochschule Hannover Neurochirurgische Klinik
Hanover, 30625
Universitätsklinik Heidelberg Neurologische Klinik
Heidelberg, 69120
Universitätsklinikum Leipzig, Neurochirurgische Klinik
Leipzig, 04103
Otto-von-Guericke-Universität, Klinik für Neurochirurgie
Magdeburg, 39120
Klinik und Poliklinik für Neurochirurgie
Münster, 48149
Klinik und Poliklinik für Neurologie
Regensburg, 93053
Brazil6 sites
Hospital de Câncer de Barretos
Barretos / SP, 14784-400
Centro Goiano de Oncologia (CGO)
Goiânia, 74223-080
Hospital Sao Vicente de Paulo
Passo Fundo, 99010-080
Hospital de Clínicas de Porto Alegre
Porto Alegre, 90035-903
Hospital Sao Lucas da PUCRS
Porto Alegre, 90610-000
Hospital do Servidor Público Estadual
São Paulo, 04038-034
Poland6 sites
Wojskowy Szpital Kliniczny, Klinika Neurochirurgii
Bydgoszcz, 85-681
Akademickie Centrum Kliniczne
Gdansk, 80-952
SP ZOZ Uniwersytecki Szpital Kliniczny nr 1, Klinika Neurochirurgii
Lodz, 91-153
Samodzielny Publiczny Szpital Kliniczny nr 4, Klinika Neurochirurgii i Neurochirurgii Dziecięcej
Lublin, 20-090
Kliniczny Oddzial Neurochirurgii SUM w Sosnowcu Wojewódzki Szpital Specjalistyczny nr 5
Sosnowiec, 41-200
Centrum Onkologii - Instytut Im. Marii Sklodowskiej-Curie
Warsaw, 02-781
Russia5 sites
Chelyabinsk City Hospital #3; Department of Neurosurgery
Chelyabinsk, 454021
State Institution Russian Oncology Research Center N.N. Blokhin
Moscow, 115478
Russian Scientific Research Neurosurgical Institute A.L. Polenov
Saint Petersburg, 191104
Military Medical Academy, Neurosurgery Dept
Saint Petersburg, 194044
Samara Region Clinical Hospital M.I. Kalinin
Samara, 443095
Spain5 sites
Hospital de Cruces
Barakaldo, 48903
Hospital Universitario Vall d'Hebron
Barcelona, 08035
Hospital Doce de Octubre
Madrid, 28041
Hospital Universitario Marqués de Valdecilla
Santander, 39008
Hospital Universitario Virgen del Rocío
Seville, 41013
United States3 sites
NJ Neuroscience Institute; JFK Medical Center
Edison, New Jersey, 08820
Winthrop University Hospital
Mineola, New York, 11501
University of Rochester Medical Center
Rochester, New York, 14642
Argentina3 sites
Hospital Británico
Buenos Aires, C1280AEB
FLENI
Buenos Aires, C1428
Sanatorio Allende
Córdoba, X5000JHQ
Canada3 sites
Foothills Medical Centre
Calgary, AB T2N 2T9
ECOGENE-21 Centre d'études cliniques
Chicoutimi, Quebec, G7H 7P2
Montreal Neurological Institute and Hospital
Montreal, H3A 2B4
Mexico3 sites
Hospital San Javier
Guadalajara, 44670
Hospital General de Mexico
Mexico City, 06120
Medica Sur
Mexico City, 14050
South Korea3 sites
Severance Hospital, Yonsei University College of Medicine
Seoul, 120-752
Kangnam St. Mary's Hospital
Seoul, 137-701
Asan Medical Center
Seoul, 138-736
Taiwan3 sites
China Medical University Hospital
Taichung, 404
Taichung Veterans General Hospital
Taichung, 407
Tri-Service General Hospital
Taipei, 114
Austria2 sites
Universitätsklinik Innsbruck, Abteilung für Neurologie
Innsbruck, 6020
AKH Wien, Klinik für Neurochirurgie
Vienna, 1090
United Kingdom2 sites
Edinburgh Centre for Neuro-Oncology, Western General Hospital
Edinburgh, EH42XU
The National Hospital for Neurology and Neurosurgery
London, WC1N 3BG
Hungary1 site
Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ
Szeged, 6720
About this study
Official 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.
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).
Read the detailed description
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.
- Conditions
- Anaplastic Astrocytoma, Glioblastoma
- Being tested
- trabedersen, temozolomide, Drug delivery system for administration of AP 12009, Placement of Drug Delivery System, carmustine
- Keywords
- Anaplastic astrocytoma, Glioblastoma, Antisense, Cancer, Transforming Growth Factor beta 2, Targeted therapy, Brain tumor, Glioma, Central Nervous System (CNS), Convection Enhanced Delivery (CED), Intratumoral administration
- Medical subject headings
- Astrocytoma, Glioblastoma, Neoplasms, Brain Neoplasms, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
trabedersenDrug
Also called AP 12009
temozolomideDrug
Also called Temodar, Temodal, TMZ
Drug delivery system for administration of AP 12009Device
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 SystemProcedure or surgery
Surgery for placement of intratumoral catheter and subcutaneous port access system as per routine clinical practice. Stereotactical catheter placement controlled by CT.
carmustineDrug
Also called BCNU, BiCNU, Carmubris
lomustineDrug
Also called CCNU, CeeNU
| Study group | Role | What they receive |
|---|---|---|
| trabedersen 10 µM | Experimental | 10 µM trabedersen (AP 12009), intratumoral infusion, every other week, 11 cycles, maximum 21 weeks Receives: Drug: trabedersen; Device: Drug delivery system for administration of AP 12009; Procedure: Placement of Drug Delivery System |
| 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. Receives: Drug: temozolomide; Drug: carmustine; Drug: lomustine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 24 months
Secondary outcomes (10)
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.
Measured: 12, 18, and 21 months
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.
Measured: 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.
Measured: 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:
- Complete Response (CR): Disappearance of all enhancing tumor on consecutive MRI scans at least 1 month apart, off steroids, neurologically stable or improved.
- Partial Response (PR): ≥50% reduction in size of enhancing tumor on consecutive MRI scans at least 1 month apart, steroids stable or reduced, neurologically stable or improved.
- Progressive Disease (PD): ≥25% increase in size of enhancing tumor or any new tumor on MRI scans, steroids stable or increased, neurologically worse.
- Stable Disease (SD): all other situations.
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.
Measured: 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.
Measured: 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.
Measured: 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:
- at the date of randomization -- participants without baseline assessments, or for those with no post-baseline timor assessments who were discontinued for other than progressive disease or death.
- at the date of last tumor assessment -- discontinuation other than PD or death, or if a new treatment was started prior to disease progression
- at the date of death or last tumor assessment -- death or PD after one missed tumor assessment
- at the date of last tumor assessment -- death or PD after more than one missed tumor assessment
- at the date of last tumor assessment -- participants on ongoing treatment at data cut-off
Measured: 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:
- Complete Response (CR): Disappearance of all enhancing tumor on consecutive MRI scans at least 1 month apart, off steroids, neurologically stable or improved.
- Partial Response (PR): ≥50% reduction in size of enhancing tumor on consecutive MRI scans at least 1 month apart, steroids stable or reduced, neurologically stable or improved.
- Progressive Disease (PD): ≥25% increase in size of enhancing tumor or any new tumor on MRI scans, steroids stable or increased, neurologically worse.
- Stable Disease (SD): all other situations.
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.
Measured: 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:
- Complete Response (CR): Disappearance of all enhancing tumor on consecutive MRI scans at least 1 month apart, off steroids, neurologically stable or improved.
- Partial Response (PR): ≥50% reduction in size of enhancing tumor on consecutive MRI scans at least 1 month apart, steroids stable or reduced, neurologically stable or improved.
- Progressive Disease (PD): ≥25% increase in size of enhancing tumor or any new tumor on MRI scans, steroids stable or increased, neurologically worse.
- Stable Disease (SD): all other situations.
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.
Measured: 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.
Measured: Up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2008 (estimated)
- Study startDec 2008
- Primary completionFeb 2012
- Study completionJun 2012
Why it stopped: Unable to recruit the projected patient number. All analyses are descriptive, only.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Anaplastic AstrocytomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Isarna Therapeutics GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Rolando Del Maestro, MD, PhD, Study chair, Montreal Neurological Institute and Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00761280
- Sponsor's protocol ID
- AP 12009-G005
- Acronym
- SAPPHIRE
- Status last verified
- Nov 2014
- First submitted
- 26 Sep 2008
- Last updated
- 14 Nov 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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.
- ClinicalTrials.gov ID
- NCT00761280
- Acronym / sponsor ID
- SAPPHIRE / AP 12009-G005
- Conditions
- Anaplastic Astrocytoma, Glioblastoma
- Keywords
- Anaplastic astrocytoma, Glioblastoma, Antisense, Cancer, Transforming Growth Factor beta 2, Targeted therapy, Brain tumor, Glioma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Unable to recruit the projected patient number. All analyses are descriptive, only.
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Isarna Therapeutics GmbHIndustry (pharma, biotech, devices)
- Study start
- Dec 2008
- Primary completion
- Feb 2012 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 29 Sep 2008 (estimated)
- Results
- Posted 22 Aug 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| trabedersen 10 µM | Experimental | Drug: trabedersen, Device: Drug delivery system for administration of AP 12009, Procedure: Placement of Drug Delivery System10 µM trabedersen (AP 12009), intratumoral infusion, every other week, 11 cycles, maximum 21 weeks |
| Chemotherapy | Active comparator | Drug: temozolomide, Drug: carmustine, Drug: lomustinetemozolomide: 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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- 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).
Key exclusion criteria (23 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| trabedersenAlso: AP 12009 | Drug | trabedersen 10 µM |
| temozolomideAlso: Temodar, Temodal, TMZ | Drug | Chemotherapy |
| Drug delivery system for administration of AP 12009Drug 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). | Device | trabedersen 10 µM |
| Placement of Drug Delivery SystemSurgery for placement of intratumoral catheter and subcutaneous port access system as per routine clinical practice. Stereotactical catheter placement controlled by CT. | Procedure or surgery | trabedersen 10 µM |
| carmustineAlso: BCNU, BiCNU, Carmubris | Drug | Chemotherapy |
| lomustineAlso: CCNU, CeeNU | Drug | Chemotherapy |
Primary outcome
Survival Rate at 24 Months in the Intent-to-treat Population - Percentage of Participants (Descriptive Analysis, Only)
Time frame: 24 months
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.
Survival at 24 Months in the Intent-to-treat Population - Number of Participants
Time frame: 24 months
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.
10 secondary outcomes
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
Survival at 12, 18, and 21 Months in the Intent-to-treat Population - Number of Participants
Time frame: 12, 18, and 21 months
Median Overall Survival (Days) From Randomization in the Intent-to-treat Population (Descriptive Analysis, Only)
Time frame: Up to 24 months
Response Category by Independent Review in the Intent-to-treat Population - Number of Participants
Time frame: Up to 24 months
Overall Response Rate (CR+PR) by Independent Review in the Intent-to-treat Population - Percentage of Participants (Descriptive Analysis, Only)
Time frame: 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)
Time frame: Up to 24 months
Median Duration of Response (Days) by Independent Review (Descriptive Analysis, Only)
Time frame: 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
Time frame: 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)
Time frame: 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 frame: Up to 24 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rolando Del Maestro, MD, PhD study chair
Montreal Neurological Institute and Hospital
68 sites in 16 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing trabedersen, temozolomide and Drug delivery system for administration of AP 12009 in people with Anaplastic Astrocytoma and Glioblastoma, run by Isarna Therapeutics GmbH at 68 sites in 16 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 14 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 68 sites in India, Germany, Brazil, Poland, Russia and 11 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Aug 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Survival Rate at 24 Months in the Intent-to-treat Population - Percentage of Participants (Descriptive Analysis, Only) (time frame: 24 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2014.