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

Study Purpose

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).

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

 No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

 Interventional
Eligible Ages 18 Years - 70 Years
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - The patient has provided written informed consent prior to any study-related procedure.
  • - The patient is at least 18 years of age and equal to or below 70 years.
  • - The patient has a present diagnosis of AA or secondary GBM.
  • - The patient has a measurable lesion (> 1 ccm in volume, central MRI review).
  • - The lesion (or sum of lesions) does not exceed 50 ccm in volume (central MRI review).
  • - The tumor is localized supratentorially (central MRI review).
  • - All patients have recurrent or refractory disease, i.e. disease has progressed after prior surgery and radiotherapy at any time of the disease course or stage.
Secondary GBM patients have progressed after a previous diagnosis of A and/or AA.
  • - The patient has not received more than one chemotherapy regimen.
Radiation with concomitant chemotherapy, followed by adjuvant chemotherapy, is considered as one chemotherapy regimen.
  • - The patient is eligible for chemotherapy.
  • - The patient is on a maximum dose of 4 mg/day dexamethasone or equivalent doses for other corticosteroids, which has been stable or decreasing for at least 3 weeks prior to Screening.
  • - The patient is male or a non-pregnant, non-lactating female.
  • - Females of childbearing potential must have a negative beta-HCG pregnancy test at Screening.
  • - Females of childbearing potential and males must practice strict birth control.
  • - The patient must have recovered from acute toxicity caused by any previous therapy.
  • - The patient has a life expectancy of at least 3 months.
  • - The patient has a Karnofsky Performance Status of at least 70%.
  • - The patient shows adequate organ functions as assessed by the following screening laboratory values: 1.
Adequate renal function determined by serum creatinine and urea < 2 times the upper limit of normal. 2. Adequate liver function with ALT, AST and AP < 3 times the upper limit of normal, and bilirubin < 2.5 mg/dL. 3. INR < 1.5 and aPTT < 1.5 x ULN. 4. Hemoglobin > 9 g/dL. 5. Platelet count > 100 x 10E9/L. 6. WBC > 3 x 10E9/L. 7. ANC > 1.5 x 10E9/L (or WBC > 3.0 x 10E9/L)

Exclusion Criteria:

  • - Patient unable or not willing to comply with the protocol regulations.
  • - The investigator deems it necessary to surgically (re-)resect the present tumor (NOTE: the patient might still be eligible for randomization at a later timepoint).
  • - Tumor surgery, tumor debulking, or other neurosurgery within 3 months prior to randomization.
If a ≤48-hour routine post-surgery MRI (in accordance with study specifications) qualifies the patient for study participation, the patient can be randomized 30 ± 7 days post-surgery.
  • - Radiotherapy or stereotactic (gamma knife) radiosurgery within 3 months prior to randomization.
  • - Prior interstitial brachytherapy of the brain with permanent implants.
Prior interstitial brachytherapy of the brain with removable implants within 3 months prior to randomization.
  • - Chemotherapy, hormone therapy, or any other therapy with established or suggested anti-tumor effects within 4 weeks (nitrosoureas: 6 weeks) prior to randomization.
  • - Prior anti-TGF-beta 2 targeted therapy.
  • - Screening MRI shows a mass effect caused by the tumor defined as significant compression of the ventricular system and/or a midline shift (≥ 3 mm, central MRI review).
Compression of the ventricular system and/or a midline shift ≥ 3 mm only due to the presence of (a) cyst(s) or scarring processes does not exclude an individual from the study.
  • - Participation in another clinical study with another investigational medicinal product within 30 days prior to randomization.
  • - History of a second independent malignant disorder within 5 years, except for carcinoma in situ of the cervix and basal cell carcinoma.
  • - Presence of poorly controlled seizures.
  • - Clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure, unstable angina, or poorly controlled arrhythmia.
Myocardial infarction within 6 months prior to randomization.
  • - Known HIV, HBV or HCV infection.
  • - Acute viral, bacterial, or fungal infection.
  • - Acute medical problems that may be considered to become an unacceptable risk, or any conditions, which might be contraindications for starting study treatment.
  • - Presence of high risk for pulmonary toxicities, defined as: 1.
Lung function: vital capacity ≤ 70% 2. Status following sequential or concomitant thoracic irradiation. 3. Increased risk for a pulmonary toxicity induced by BCNU (Carmustine) or CCNU (Lomustine). Risk factors include smoking, presence of a respiratory condition, pre-existing radiographic pulmonary abnormalities, exposure to agents that cause lung damage.
  • - History of allergies to reagents used in this study, history of celiac disease.
  • - Drug abuse or extensive use of alcohol.
  • - Clinically relevant psychiatric disorders / legal incapacity or a limited legal capacity.
  • - Concomitant treatment with yellow fever vaccine.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

 NCT00761280
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

 Phase 3
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

 Isarna Therapeutics GmbH
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

 Rolando Del Maestro, MD, PhD
Principal Investigator Affiliation Montreal Neurological Institute and Hospital
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

 Industry
Overall Status Terminated
Countries Argentina, Austria, Brazil, Canada, France, Germany, Hungary, India, Korea, Republic of, Mexico, Poland, Russian Federation, Spain, Taiwan, United Kingdom, United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

 Anaplastic Astrocytoma, Glioblastoma
Additional Details

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.

Arms & Interventions

Arms

Experimental: trabedersen 10 µM

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

Active Comparator: Chemotherapy

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.

Interventions

Drug: - trabedersen

Drug: - temozolomide

Device: - 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).

Procedure: - 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.

Drug: - carmustine

Drug: - lomustine

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Edison, New Jersey

Status

Address

NJ Neuroscience Institute; JFK Medical Center

Edison, New Jersey, 08820

Winthrop University Hospital, Mineola, New York

Status

Address

Winthrop University Hospital

Mineola, New York, 11501

University of Rochester Medical Center, Rochester, New York

Status

Address

University of Rochester Medical Center

Rochester, New York, 14642

International Sites

Hospital Británico, Ciudad Autónoma de Buenos Aires, Argentina

Status

Address

Hospital Británico

Ciudad Autónoma de Buenos Aires, , C1280AEB

FLENI, Ciudad Autónoma de Buenos Aires, Argentina

Status

Address

FLENI

Ciudad Autónoma de Buenos Aires, , C1428

Sanatorio Allende, Córdoba, Argentina

Status

Address

Sanatorio Allende

Córdoba, , X5000JHQ

Innsbruck, Austria

Status

Address

Universitätsklinik Innsbruck, Abteilung für Neurologie

Innsbruck, , 6020

AKH Wien, Klinik für Neurochirurgie, Wien, Austria

Status

Address

AKH Wien, Klinik für Neurochirurgie

Wien, , 1090

Hospital de Câncer de Barretos, Barretos / SP, Brazil

Status

Address

Hospital de Câncer de Barretos

Barretos / SP, , 14784-400

Centro Goiano de Oncologia (CGO), Goiania, Brazil

Status

Address

Centro Goiano de Oncologia (CGO)

Goiania, , 74223-080

Hospital Sao Vicente de Paulo, Passo Fundo, Brazil

Status

Address

Hospital Sao Vicente de Paulo

Passo Fundo, , 99010-080

Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil

Status

Address

Hospital de Clínicas de Porto Alegre

Porto Alegre, , 90035-903

Hospital Sao Lucas da PUCRS, Porto Alegre, Brazil

Status

Address

Hospital Sao Lucas da PUCRS

Porto Alegre, , 90610-000

Hospital do Servidor Público Estadual, Sao Paulo, Brazil

Status

Address

Hospital do Servidor Público Estadual

Sao Paulo, , 04038-034

ECOGENE-21 Centre d'études cliniques, Chicoutimi, Quebec, Canada

Status

Address

ECOGENE-21 Centre d'études cliniques

Chicoutimi, Quebec, G7H 7P2

Foothills Medical Centre, Calgary, Canada

Status

Address

Foothills Medical Centre

Calgary, , AB T2N 2T9

Montreal, Canada

Status

Address

Montreal Neurological Institute and Hospital

Montreal, , H3A 2B4

La Timone University Hospital, Marseille, France

Status

Address

La Timone University Hospital

Marseille, , 13385

Klinik und Poliklinik für Neurochirurgie, Frankfurt/M., Germany

Status

Address

Klinik und Poliklinik für Neurochirurgie

Frankfurt/M., , 60528

Universitätsklinikum Freiburg, Freiburg, Germany

Status

Address

Universitätsklinikum Freiburg

Freiburg, , 79106

Günzburg, Germany

Status

Address

Neurochirurgische Klinik an der Universität Ulm am Bezirkskrankenhaus Günzburg

Günzburg, , 89312

Hamburg, Germany

Status

Address

Universitätklinikum Hamburg-Eppendorf, Klinik für Neurochirurgie

Hamburg, , 20246

Hannover, Germany

Status

Address

Medizinische Hochschule Hannover Neurochirurgische Klinik

Hannover, , 30625

Heidelberg, Germany

Status

Address

Universitätsklinik Heidelberg Neurologische Klinik

Heidelberg, , 69120

Leipzig, Germany

Status

Address

Universitätsklinikum Leipzig, Neurochirurgische Klinik

Leipzig, , 04103

Magdeburg, Germany

Status

Address

Otto-von-Guericke-Universität, Klinik für Neurochirurgie

Magdeburg, , 39120

Klinik und Poliklinik für Neurochirurgie, Münster, Germany

Status

Address

Klinik und Poliklinik für Neurochirurgie

Münster, , 48149

Klinik und Poliklinik für Neurologie, Regensburg, Germany

Status

Address

Klinik und Poliklinik für Neurologie

Regensburg, , 93053

Szeged, Hungary

Status

Address

Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ

Szeged, , 6720

Bangalore, India

Status

Address

Manipal Hospital & Manipal Institute for Neurological Disorders

Bangalore, , 560017

NIMHANS, Bangalore, India

Status

Address

NIMHANS

Bangalore, , 560029

BGS Global Hospital, Bangalore, India

Status

Address

BGS Global Hospital

Bangalore, , 560060

Chandigarh, India

Status

Address

Postgraduate Institute of Medical Education & Research (PGIMER)

Chandigarh, , 160012

Apollo Speciality Hospitals, Chennai, India

Status

Address

Apollo Speciality Hospitals

Chennai, , 600006

Cochin, India

Status

Address

Amrita Institute of Medical Sciences Research Center

Cochin, , 560017

Care Hospitals, Hyderabaad, India

Status

Address

Care Hospitals

Hyderabaad, , 500034

AMRI Hospitals, Kolkata, India

Status

Address

AMRI Hospitals

Kolkata, , 700029

SGPGI of Medical Sciences, Lucknow, India

Status

Address

SGPGI of Medical Sciences

Lucknow, , 226014

Mumbai, India

Status

Address

Advanced Centre for Treatment Research and Education in Cancer (ACTREC)

Mumbai, , 410210

New Delhi, India

Status

Address

All India Institute of Medical Sciences (AIIMS)

New Delhi, , 110029

SCTIMST, Dept. of Neurosurgery, Thiruvananthapuram, India

Status

Address

SCTIMST, Dept. of Neurosurgery

Thiruvananthapuram, , 695011

Seoul, Korea, Republic of

Status

Address

Severance Hospital, Yonsei University College of Medicine

Seoul, , 120-752

Kangnam St. Mary's Hospital, Seoul, Korea, Republic of

Status

Address

Kangnam St. Mary's Hospital

Seoul, , 137-701

Asan Medical Center, Seoul, Korea, Republic of

Status

Address

Asan Medical Center

Seoul, , 138-736

Hospital San Javier, Guadalajara, Mexico

Status

Address

Hospital San Javier

Guadalajara, , 44670

Hospital General de Mexico, Mexico City, Mexico

Status

Address

Hospital General de Mexico

Mexico City, , 06120

Medica Sur, Mexico City, Mexico

Status

Address

Medica Sur

Mexico City, , 14050

Bydgoszcz, Poland

Status

Address

Wojskowy Szpital Kliniczny, Klinika Neurochirurgii

Bydgoszcz, , 85-681

Akademickie Centrum Kliniczne, Gdańsk, Poland

Status

Address

Akademickie Centrum Kliniczne

Gdańsk, , 80-952

Lublin, Poland

Status

Address

Samodzielny Publiczny Szpital Kliniczny nr 4, Klinika Neurochirurgii i Neurochirurgii Dziecięcej

Lublin, , 20-090

Sosnowiec, Poland

Status

Address

Kliniczny Oddzial Neurochirurgii SUM w Sosnowcu Wojewódzki Szpital Specjalistyczny nr 5

Sosnowiec, , 41-200

Warszawa, Poland

Status

Address

Centrum Onkologii - Instytut Im. Marii Sklodowskiej-Curie

Warszawa, , 02-781

Łódź, Poland

Status

Address

SP ZOZ Uniwersytecki Szpital Kliniczny nr 1, Klinika Neurochirurgii

Łódź, , 91-153

Chelyabinsk, Russian Federation

Status

Address

Chelyabinsk City Hospital #3; Department of Neurosurgery

Chelyabinsk, , 454021

Moscow, Russian Federation

Status

Address

State Institution Russian Oncology Research Center N.N. Blokhin

Moscow, , 115478

Samara, Russian Federation

Status

Address

Samara Region Clinical Hospital M.I. Kalinin

Samara, , 443095

St. Petersburg, Russian Federation

Status

Address

Russian Scientific Research Neurosurgical Institute A.L. Polenov

St. Petersburg, , 191104

St. Petersburg, Russian Federation

Status

Address

Military Medical Academy, Neurosurgery Dept

St. Petersburg, , 194044

Hospital de Cruces, Baracaldo, Spain

Status

Address

Hospital de Cruces

Baracaldo, , 48903

Hospital Universitario Vall d'Hebron, Barcelona, Spain

Status

Address

Hospital Universitario Vall d'Hebron

Barcelona, , 08035

Hospital Doce de Octubre, Madrid, Spain

Status

Address

Hospital Doce de Octubre

Madrid, , 28041

Santander, Spain

Status

Address

Hospital Universitario Marqués de Valdecilla

Santander, , 39008

Hospital Universitario Virgen del Rocío, Sevilla, Spain

Status

Address

Hospital Universitario Virgen del Rocío

Sevilla, , 41013

China Medical University Hospital, Taichung, Taiwan

Status

Address

China Medical University Hospital

Taichung, , 404

Taichung Veterans General Hospital, Taichung, Taiwan

Status

Address

Taichung Veterans General Hospital

Taichung, , 407

Tri-Service General Hospital, Taipei City, Taiwan

Status

Address

Tri-Service General Hospital

Taipei City, , 114

Edinburgh, United Kingdom

Status

Address

Edinburgh Centre for Neuro-Oncology, Western General Hospital

Edinburgh, , EH42XU

London, United Kingdom

Status

Address

The National Hospital for Neurology and Neurosurgery

London, , WC1N 3BG

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