GlioblastomaPhase 2NCT00431561
Phase IIb Clinical Trial With TGF-β2 Antisense Compound AP 12009 for Recurrent or Refractory High-grade Glioma
A Phase 2 study testing AP 12009 10 µM, AP 12009 80 µM and temozolomide or PCV in people with Glioblastoma and Anaplastic Astrocytoma, run by Isarna Therapeutics GmbH at 36 sites in 6 countries.
Trial summary
In this multinational dose finding Phase IIb study the efficacy and safety of two doses of AP 12009 compared to standard chemotherapy (temozolomide or PCV) is investigated in adult patients with confirmed recurrent high-grade glioma. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Glioblastoma, Anaplastic Astrocytoma
- What is being tested?
- AP 12009 10 µM, AP 12009 80 µM and temozolomide or PCV
- 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
- 141 participants
- Where
- 36 sitesin 6 countries
- Study dates
- Apr 2003to Mar 2009
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histopathologically confirmed diagnosis of recurrent or refractory high-grade glioma (anaplastic astrocytoma, WHO grade III; or glioblastoma, WHO grade IV)
- Supratentorial localization
- No more than two chemotherapy regimens including radiochemotherapy since primary diagnosis
- Eligible for either TMZ or PCV treatment
- Recovery from acute toxicity caused by any previous therapy
- Adequate organ functions
- KPS at least 70%
Who cannot join
- Tumor surgery within 2 weeks prior to study entry
- Radiation therapy within 8 weeks prior to study entry
- Chemotherapy within 4 weeks prior to study entry (nitrosureas: 6 weeks)
- No more than 3 mg/day dexamethasone (or equivalent) at baseline
- Prior TGF-beta targeted therapy or tumor vaccination
- Baseline MRI shows mass effect
- Known active infection with HIV, HBV, or HCV; acute viral, bacterial, or fungal infection
- Significant psychiatric disorders/legal incapacity or a limited legal capacity
Trial locations and contacts
36 sites in 6 countries.
36 sites in 6 countries
Germany12 sites
Medizinische Klinik und Poliklinik mit Schwerpunkt Onkologie und Hämatologie, Charité Campus Mitte
Berlin, 10117
Klinik und Poliklinik für Neurologie
Cottbus, 03048
Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden
Dresden, 01307
Universitätsklinikum Gießen, Neurochirurgische Universitätsklinik
Giessen, 35392
Universitätsklinikum Kiel, Klinik für Neurochirurgie
Kiel, 24106
Universitätsklinikum Leipzig, Klinik und Poliklinik für Neurochirurgie
Leipzig, 04103
Universitätsklinik Magdeburg, Klinik für Neurochirurgie
Magdeburg, 39120
Universitätskliniken Mainz, Neurochirurgische Klinik und Poliklinik
Mainz, 55131
Universitätsklinikum Münster, Klinik und Poliklinik für Neurochirurgie
Münster, 48149
Klinikum und Poliklinik für Neurologie, Universität Regensburg
Regensburg, 93053
Klinikum Saarbrücken, Neurochirurgie
Saarbrücken, 66119
Neurologische Universitätsklinik Tübingen
Tübingen, 72076
Russia9 sites
Tcheliabinsk Regional Clinical Hospital; State Medical Institution for Prophylaxis and Treatment
Chelyabinsk, 454076
Republican Clinical Hospital of Ministry of Health of Tatarstan Republic
Kazan', 420064
Burdenko Neurosurgery Research Institute
Moscow, 125047
Omsk State Medical Academy; State Educational Institution of Higher Professional Education
Omsk, 644099
Polenov Neurosurgery Research Institute
Saint Petersburg, 191104
Military Medical Academy named after I.S.M. Kirov, Neurosurgery Department
Saint Petersburg, 194175
Medical Center "XXI century"
Saint Petersburg, 194354
State Institution of Healthcare, Samara Regional Clinical Hospital in the name of M.I. Kalinin
Samara, 443095
Sverdlovsk Regional Oncological Clinic
Yekaterinburg, 620036
India8 sites
Manipal Hospital; Manipal Institute for Neurological Disorders
Bangalore, 560017
Department of Neurosurgery, National Institute of Mental Health and Neurosciences
Bangalore, 560029
Department of Medical Oncology, Nizam's Institute of Medical Sciences
Hyderabad, 500082
Department of Neurosurgery, Amrita Institute of Medical Sciences & Research Centre
Kochi, Kerala, 682026
Department of Neurosurgery, LTMG Hospital & LTM Medical College
Mumbai, 400022
Department of Neurosurgery, Neurosciences Center
New Dehli, 110029
Sree Chitra Tirunal Institute for Medical Sciences & Technology, Department of Neurosurgery
Trivandrum, Kerala, 695011
Department of Neurological Sciences, Christian Medical College & Hospital
Vellore, 632004
Austria3 sites
Universitätsklinik Innsbruck; Abteilung für Neurochirurgie
Innsbruck, 6020
Landes-Nervenklinik Wagner-Jauregg
Linz, 4020
Kaiser Franz Josef Spital, Abteilung für Neurologie
Vienna, 1100
Israel3 sites
Soroka Medical Center, Neurosurgery Department
Beersheba
Rambam Medical Center, Neurosurgery Department
Haifa, 31096
Rabin Medical Center, Neurosurgery Department
Petah Tikva, 49100
Georgia1 site
Sarajishvili Institute of Clinical Neurology and Neurosurgery
Tbilisi, 0114
About this study
Official title: Multi-national, Open-label, Active-controlled, Randomized Dose-finding Study to Evaluate Efficacy of 2 Doses of AP 12009 in Recurrent Glioma, Administered Intratumorally as Continuous High-flow Microperfusion Over 7 Days Every Other Week
In this multinational dose finding Phase IIb study the efficacy and safety of two doses of AP 12009 compared to standard chemotherapy (temozolomide or PCV) is investigated in adult patients with confirmed recurrent high-grade glioma.
Read the detailed description
The purpose of this study is to compare the safety and efficacy of two doses of AP 12009 and standard chemotherapy in adult patients with recurrent high-grade glioma (anaplastic astrocytoma [AA], WHO grade III; or glioblastoma [GBM], WHO grade IV). AP 12009 is a phosphorothioate antisense oligodeoxynucleotide specific for the mRNA of human transforming growth factor-beta2 (TGF-beta2). 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. It has been shown that in a number of tumor types the degree of TGF-beta production strongly correlates with tumor grade and stage. In patients with high-grade glioma, the TGF-beta2 overexpression is associated with disease stage, clinical prognosis and the immunodeficient state of the patients.
- Conditions
- Glioblastoma, Anaplastic Astrocytoma
- Being tested
- AP 12009 10 µM, AP 12009 80 µM, temozolomide or PCV, Drug delivery system for administration of AP 12009, Placement of Drug Delivery System
- Keywords
- Glioblastoma, Anaplastic astrocytoma, Antisense, Cancer, Transforming growth factor beta2 (TGF-beta2), Targeted therapy, Immunotherapy, Brain tumor, Central nervous system (CNS), Convection-enhanced delivery (CED) / microperfusion, Locoregional application
- Medical subject headings
- Glioblastoma, Astrocytoma, Neoplasms, Brain Neoplasms, Camurati-Engelmann Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AP 12009 10 µMDrug
10 µM AP 12009 (trabedersen), intratumoral infusion, every other week, 11 cycles, maximum 21 weeks
AP 12009 80 µMDrug
80 µM AP 12009 (trabedersen), intratumoral infusion, every other week, 11 cycles, maximum 21 weeks
temozolomide or PCVDrug
Also called Temodar, Temodal, TMZ, lomustine
temozolomide: capsules, up to 200 mg/sqm/day, 5 days per cycle; PCV (procarbazine, CCNU, vincristine): standard regimen
Drug delivery system for administration of AP 12009Device
Drug delivery system for Convection Enhanced Delivery consists of a portable pump with drug reservoir and infusion line. Main implanted parts are the port access system and the intratumoral 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.
| Study group | Role | What they receive |
|---|---|---|
| AP 12009 10 µM | Experimental | Not described Receives: Drug: AP 12009 10 µM; Device: Drug delivery system for administration of AP 12009; Procedure: Placement of Drug Delivery System |
| AP 12009 80 µM | Experimental | Not described Receives: Drug: AP 12009 80 µM; Device: Drug delivery system for administration of AP 12009; Procedure: Placement of Drug Delivery System |
| Chemotherapy | Active comparator | Not described Receives: Drug: temozolomide or PCV |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate of two AP 12009 dose groups and control group assessed by the evaluation of tumor size on brain MRI scans
Secondary outcomes (10)
Overall survival
Measured: overall
Overall survival
Measured: six- and twelve-month
Response rates
Measured: at 3, 8, 10, and 12 months (and during the prolonged follow-up period in six-monthly intervals, if applicable)
Progression-free survival
Measured: six-month
Time to progression
Time to response
Best of all response rates assessed by survival status and variation of tumor size on brain MRI
Change of quality of life and Karnofsky Performance Status (KPS)
Measured: at 3, 8, 10, and 12 months (and during the prolonged follow-up period in six-monthly intervals, if applicable)
Best of all response rates
Safety and tolerability
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2007 (estimated)
- Study startApr 2003
- Primary completionMar 2009
- Study completionMar 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for GlioblastomaStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 141 participants (actual)
Sponsor and investigators
- Lead sponsor
- Isarna Therapeutics GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Ulrich Bogdahn, MD, Principal investigator, University of Regensburg, Dept. of Neurology, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00431561
- Sponsor's protocol ID
- AP 12009-G004
- Status last verified
- Dec 2013
- First submitted
- 5 Feb 2007
- Last updated
- 3 Dec 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Uckun FM, Qazi S, Hwang L, Trieu VN. Recurrent or Refractory High-Grade Gliomas Treated by Convection-Enhanced Delivery of a TGFbeta2-Targeting RNA Therapeutic: A Post-Hoc Analysis with Long-Term Follow-Up. Cancers (Basel). 2019 Nov 28;11(12):1892. doi: 10.3390/cancers11121892.
PubMed 31795071
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multi-national, Open-label, Active-controlled, Randomized Dose-finding Study to Evaluate Efficacy of 2 Doses of AP 12009 in Recurrent Glioma, Administered Intratumorally as Continuous High-flow Microperfusion Over 7 Days Every Other Week
- ClinicalTrials.gov ID
- NCT00431561
- Acronym / sponsor ID
- AP 12009-G004
- Conditions
- Glioblastoma, Anaplastic Astrocytoma
- Keywords
- Glioblastoma, Anaplastic astrocytoma, Antisense, Cancer, Transforming growth factor beta2 (TGF-beta2), Targeted therapy, Immunotherapy, Brain tumor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 141 participants (actual)
- Lead sponsor
- Isarna Therapeutics GmbHIndustry (pharma, biotech, devices)
- Study start
- Apr 2003
- Primary completion
- Mar 2009 (actual)
- Study completion
- Mar 2009 (actual)
- First posted
- 6 Feb 2007 (estimated)
- Results
- Not posted in the source record
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 dose finding Phase IIb study the efficacy and safety of two doses of AP 12009 compared to standard chemotherapy (temozolomide or PCV) is investigated in adult patients with confirmed recurrent high-grade glioma.
Detailed description
The purpose of this study is to compare the safety and efficacy of two doses of AP 12009 and standard chemotherapy in adult patients with recurrent high-grade glioma (anaplastic astrocytoma [AA], WHO grade III; or glioblastoma [GBM], WHO grade IV). AP 12009 is a phosphorothioate antisense oligodeoxynucleotide specific for the mRNA of human transforming growth factor-beta2 (TGF-beta2). 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. It has been shown that in a number of tumor types the degree of TGF-beta production strongly correlates with tumor grade and stage. In patients with high-grade glioma, the TGF-beta2 overexpression is associated with disease stage, clinical prognosis and the immunodeficient state of the patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| AP 12009 10 µM | Experimental | Drug: AP 12009 10 µM, Device: Drug delivery system for administration of AP 12009, Procedure: Placement of Drug Delivery System |
| AP 12009 80 µM | Experimental | Drug: AP 12009 80 µM, Device: Drug delivery system for administration of AP 12009, Procedure: Placement of Drug Delivery System |
| Chemotherapy | Active comparator | Drug: temozolomide or PCV |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Histopathologically confirmed diagnosis of recurrent or refractory high-grade glioma (anaplastic astrocytoma, WHO grade III; or glioblastoma, WHO grade IV)
- Supratentorial localization
- No more than two chemotherapy regimens including radiochemotherapy since primary diagnosis
- Eligible for either TMZ or PCV treatment
- Recovery from acute toxicity caused by any previous therapy
Key exclusion criteria (8 listed)
- Tumor surgery within 2 weeks prior to study entry
- Radiation therapy within 8 weeks prior to study entry
- Chemotherapy within 4 weeks prior to study entry (nitrosureas: 6 weeks)
- No more than 3 mg/day dexamethasone (or equivalent) at baseline
- Prior TGF-beta targeted therapy or tumor vaccination
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 |
|---|---|---|
| AP 12009 10 µM10 µM AP 12009 (trabedersen), intratumoral infusion, every other week, 11 cycles, maximum 21 weeks | Drug | AP 12009 10 µM |
| AP 12009 80 µM80 µM AP 12009 (trabedersen), intratumoral infusion, every other week, 11 cycles, maximum 21 weeks | Drug | AP 12009 80 µM |
| temozolomide or PCVAlso: Temodar, Temodal, TMZ, lomustinetemozolomide: capsules, up to 200 mg/sqm/day, 5 days per cycle; PCV (procarbazine, CCNU, vincristine): standard regimen | Drug | Chemotherapy |
| Drug delivery system for administration of AP 12009Drug delivery system for Convection Enhanced Delivery consists of a portable pump with drug reservoir and infusion line. Main implanted parts are the port access system and the intratumoral catheter. | Device | AP 12009 10 µM, AP 12009 80 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 | AP 12009 10 µM, AP 12009 80 µM |
Primary outcome
Overall response rate of two AP 12009 dose groups and control group assessed by the evaluation of tumor size on brain MRI scans
10 secondary outcomes
Overall survival
Time frame: overall
Overall survival
Time frame: six- and twelve-month
Response rates
Time frame: at 3, 8, 10, and 12 months (and during the prolonged follow-up period in six-monthly intervals, if applicable)
Progression-free survival
Time frame: six-month
Time to progression
Time to response
Best of all response rates assessed by survival status and variation of tumor size on brain MRI
Change of quality of life and Karnofsky Performance Status (KPS)
Time frame: at 3, 8, 10, and 12 months (and during the prolonged follow-up period in six-monthly intervals, if applicable)
Best of all response rates
Safety and tolerability
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2013.
- Derived from this study: PubMed 31795071Uckun FM, Qazi S, Hwang L, Trieu VN. Recurrent or Refractory High-Grade Gliomas Treated by Convection-Enhanced Delivery of a TGFbeta2-Targeting RNA Therapeutic: A Post-Hoc Analysis with Long-Term Follow-Up. Cancers (Basel). 2019 Nov 28;11(12):1892. doi: 10.3390/cancers11121892.
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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.
Ulrich Bogdahn, MD principal investigator
University of Regensburg, Dept. of Neurology, Germany
36 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AP 12009 10 µM, AP 12009 80 µM and temozolomide or PCV in people with Glioblastoma and Anaplastic Astrocytoma, run by Isarna Therapeutics GmbH at 36 sites in 6 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 7 inclusion and 8 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: finished, as of the sponsor's last update on 3 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 36 sites in Germany, Russia, India, Austria, Israel and 1 more country. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Overall response rate of two AP 12009 dose groups and control group assessed by the evaluation of tumor size on brain MRI scans. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00431561, which also lists 1 linked publication.
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 3 Dec 2013.