Studie: Poly ICLC in the Management of Gliomas - Phase 2/3

Poly ICLC in the Management of Malignant Gliomas Phase 2/3

Min Karnofsky Score: Not Specified
Conditions:
Prior Surgery is Not Specified
Prior Radiation is Not Specified
Prior Chemotherapy is Not Specified
For Military Medical System Beneficiaries Only.

Last Updated: 04/01/2003
Comments: Phase 1 trial data remains unpublished. Follow-up multi-center studies now in planning stage. Editor´s note: these new centers may allow non-military people. Early results look good.

Contact: Dr.Andres M. Salazar MD
CEO (Act.)
Oncovir, Inc
3203 Cleveland Ave., NW
Washington, DC 20008-3450 USA
Phone: (202)248-2324
Fax: (202)248-2324




NABTC 01-06
A Phase II trial of Poly ICLC in Patients with Recurrent Anaplastic Glioma

STATUS
Cancer Type Drug Study Phase Recruiting Status Last Updated
Anaplastic Astrocytoma (AA)
Anaplastice Oligodendroglioma (AO)
Anaplastic Mixed Oligoastrocytoma (AMO)
Anaplastic Glioma Poly-ICLC
II Pending 10/02

PRINCIPAL INVESTIGATOR


Dr. Karen Fink, M.D.
The University of Texas, Southwestern (Dallas, TX)


OBJECTIVES

Primary objective: To determine the efficacy of Poly-ICLC in patients with recurrent anaplastic glioma as determined by 6 month progression free survival.
Secondary objectives:
To determine the safety profile of the phase II dose of Poly-ICLC in patients with recurrent anaplastic glioma.
To assess survival in patients with recurrent anaplastic glioma treated with Poly-ICLC.
To assess tumor response rate.
To further characterize the biological effects of Poly- ICLC


ELIGIBILITY CRITERIA

Patients with biopsy proven anaplastic glioma will be eligible for this protocol. Anaplastic gliomas include: Anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), anaplastic mixed oligoastrocytoma (AMO), or other anaplastic glioma.
Patient must have failed prior radiation therapy
Patients may have had treatment for no more than 2 prior relapses.
All patients must sign an informed consent indicating that they are aware of the investigational nature of this study.
Patients must be > 18 years old.
Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible.
Patients must not have received prior therapy with Poly-ICLC.



NABTC 01-05
Phase II Trial of Poly-ICLC for Glioblastoma
STATUS

Cancer Type Drug Study Phase Recruiting Status Last Updated
Glioblastoma Multiforme (GBM)
Gliosarcoma (GS) Poly-ICLC w/ Radiotherapy
II 10/02



PRINCIPAL INVESTIGATOR


Dr. Larry Junck, M.D.
University of Michigan

PARTICIPATING INSTITUTIONS


OBJECTIVES

Primary objective: To determine the efficacy of Poly-ICLC in patients with glioblastoma multiforme (GBM) after radiotherapy.
Secondary objectives:
To assess the proportion of patients treated with Poly-ICLC surviving 12 months after diagnosis.
To determine the safety and toxicity profile of Poly-ICLC by intramuscular injection three times weekly in patients with GBM treated before, during, and after radiotherapy.
To assess progression-free survival at 6 months and median progression-free survival from date of diagnosis in patients with GBM treated with external beam radiotherapy and Poly-ICLC.
To assess treatment response to external beam radiotherapy and Poly-ICLC in patients with GBM as demonstrated by MRI or CT.
To assess changes in neurological status in patients with GBM treated with external beam radiotherapy and Poly-ICLC.

ELIGIBILITY CRITERIA

Patients will have biopsy proven Glioblastoma Multiforme (GBM) or gliosarcoma (GS).
Histologic diagnosis, established by biopsy or resection, must have occurred no more than 4 weeks prior to registration.
Patients must not have received previous radiotherapy to the brain.
Patients must not have received previous drug therapy directed against the brain tumor. Patients who received Gliadel wafers will not be eligible.
Patients must be planning to begin radiotherapy within 4 weeks of the surgical procedure that established the diagnosis. Radiotherapy must be given in accord with protocol specified guidelines. A copy of the guidelines must be given to the radiation oncologist. The radiation oncologist must agree to treat according to these guidelines. Stereotactic radiosurgery and brachytherapy will not be allowed.
Patients must be willing to forego other drug therapies against the tumor while being treated with Poly-ICLC.
All patients must sign an informed consent indicating that they are aware of the investigational nature of this study.
Patients must be > 18 years old.
Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible.

Wirkte poly-ICLC in der entscheidenden frühen Studie (Salazar et al.,1996) wirklich? Es war eine kleine Zahl, junger, stark motivierter, selbstspritzender Patienten, günstigerweise ohne bedeutende Nebenwirkungen.
Poly-ICLC, im wesentlichen eine doppelsträngige RNA (dsRNA), vergleichbar DNA (Erbsubstanz: Nukleinsäure). Auch Viren und Bakterien benutzen diese, nur oft leicht modifiziert. Bei veränderter Nukleinsäure kann in höheren Organismen, z.B. Maus oder Mensch, relativ unspezifisch abwehrend dagegen reagiert werden, z.B. durch Ausschütten von Zytokinen, die u.a. über aktivierte Makrophagen, Dendritische Zellen, Lymphozyten, das Immunsystem stimulieren können. Z.B. können veränderte DNA, nichtmethylierte CpG-Anteile wirken. Inzwischen wurden in tierischen Zellen Rezeptoren für diese fremden Produkte gefunden, die Toll-like-Rezeptoren heißen (TLR). dsRNA hat einen TLR3, Imiquot eien TLR7/8, CpG-DNA einen TLR9.
Seltsamerweise haben Zytokine, wie IL-2, IL-6, TNF ind IFN nicht korreliert mit i.m. gespritzten poly-ICLC in den oben genannten Studie. Nur der Anstieg von Serum OAS-Aktivität deutete auf eine klinische antivirale Antwort hin. In dieser Studie schnitten die Patienten, die mehr als nur einmals pro Woche gespritzt hatten besonders gut ab. Dies könnte doch eher auf eine direkte Wirkung auf den Stoffwechsel der Tumorzellen hindeuten, eher als auf eine indirekte Immunstimulation.
Zudem, wenn das Immunsystem in der Peripherie eine antitumorale Wirkung durch poly-ICLC aufgebaut hätte, wären die Ergebnisse in einer anderen Studie gegen Nierenzellkarzinom, besser verlaufen (Giantonio-BJ et al., 2001). Hier gab es bei diesem relativ immuntheraieempfindlichen Tumor unter poly-ICLC keine einzige objektive Antwort. Haben die Gliome einen spezifischen Angriffspunkt, trotz Barriere des Blutweges und fehlende Lymphwege?? Sollte man versuchen intratumoral zu spritzen? Gibt es in Deutschland noch eine ICLC-Studie? Mehr daten würden mich interessieren. (Dr. P. Möller, E-mail: kape.moeller@t-online.de)