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Phase 2a Study of AdV-tk With Standard Radiation Therapy for Malignant Glioma (BrTK02) (BrTK02)

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ClinicalTrials.gov Identifier: NCT00589875
Recruitment Status : Completed
First Posted : January 10, 2008
Last Update Posted : April 11, 2017
Sponsor:
Information provided by (Responsible Party):
Advantagene, Inc. d.b.a. Candel Therapeutics

Tracking Information
First Submitted Date  ICMJE December 27, 2007
First Posted Date  ICMJE January 10, 2008
Last Update Posted Date April 11, 2017
Study Start Date  ICMJE March 2007
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 2, 2016)
  • Expand the safety evaluation at the maximum dose of AdV-tk evaluated in a completed phase Ib study [ Time Frame: 2 months ]
  • Overall survival [ Time Frame: 5 years ]
Original Primary Outcome Measures  ICMJE
 (submitted: December 27, 2007)
Expand the safety evaluation at the maximum dose of AdV-tk evaluated in a completed phase Ib study [ Time Frame: 2 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 2, 2016)
  • Progression free survival [ Time Frame: 24 months ]
  • Quality of life [ Time Frame: 24 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 27, 2007)
  • Overall survival [ Time Frame: 24 motnhs ]
  • Progression free survival [ Time Frame: 24 months ]
  • Quality of life [ Time Frame: 24 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 2a Study of AdV-tk With Standard Radiation Therapy for Malignant Glioma (BrTK02)
Official Title  ICMJE A Phase 2a Study of AdV-tk + Valacyclovir Gene Therapy in Combination With Standard Radiation Therapy for Malignant Glioma
Brief Summary The purpose of this study was to evaluate the safety and potential efficacy of Gene Mediated Cytotoxic Immunotherapy for malignant gliomas. The approach used an adenoviral vector (disabled virus) engineered to express the Herpes thymidine kinase gene (aglatimagene besadenovec, AdV-tk), followed by an antiherpetic prodrug, valacyclovir. The AdV-tk vector was injected into the resection bed after standard tumor surgery and valacyclovir pills were taken for 14 days. Standard radiation and chemotherapy were administered which have been shown to work cooperatively with AdV-tk + prodrug to kill tumor cells. The hypothesis is that this combination therapy can be safely delivered and will lead to improvement in the clinical outcome for patients with newly diagnosed malignant gliomas, including glioblastoma multiforme (WHO grade IV) and anaplastic astrocytomas (WHO grade III).
Detailed Description Patients had resectable or partially resectable malignant glioma and received injection of AdV-tk into remaining tumor or tumor bed after resection. Pathologic confirmation of malignant glioma must be made prior to AdV-tk injection; if this was not possible, the injection was not performed and the subject was no longer eligible for the study. The oral prodrug, valacyclovir, started 1-3 days after AdV-tk injection and continued for 14 days. Standard radiotherapy began on average 7 days after AdV-tk injection for the up-front course. Patients received temozolomide as per standard of care after completion of prodrug.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Malignant Glioma
  • Glioblastoma Multiforme
  • Anaplastic Astrocytoma
Intervention  ICMJE
  • Biological: AdV-tk
    Single dose of 3x10e11 vector particles of AdV-tk delivered to the tumor bed after resection on day 0.
  • Drug: Valacyclovir
    Single course of valacyclovir at dose of 2 grams orally three times per day for 14 days starting on day 1-3
    Other Name: Valtrex
Study Arms  ICMJE Experimental: Single arm
This study is an extension of evaluation of the surgical resection arm, Arm B, from a phase Ib study in which dose escalation on arm B was completed.
Interventions:
  • Biological: AdV-tk
  • Drug: Valacyclovir
Publications * Wheeler LA, Manzanera AG, Bell SD, Cavaliere R, McGregor JM, Grecula JC, Newton HB, Lo SS, Badie B, Portnow J, Teh BS, Trask TW, Baskin DS, New PZ, Aguilar LK, Aguilar-Cordova E, Chiocca EA. Phase II multicenter study of gene-mediated cytotoxic immunotherapy as adjuvant to surgical resection for newly diagnosed malignant glioma. Neuro Oncol. 2016 Aug;18(8):1137-45. doi: 10.1093/neuonc/now002. Epub 2016 Feb 2.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 24, 2010)
52
Original Estimated Enrollment  ICMJE
 (submitted: December 27, 2007)
24
Actual Study Completion Date  ICMJE August 2016
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Must have presumed resectable or partially resectable malignant glioma based on clinical and radiologic evaluation (pathologic confirmation of malignant glioma must be made at the time of surgery if not previously determined). Patients who have previously received AdV-tk + prodrug on this study may receive an additional AdV-tk + prodrug course at recurrence if eligibility criteria are still met.
  • Tumor must be accessible for injection and must not be located in the brainstem, midbrain, contained within the ventricular system, or located in an infratentorial location.
  • Must be planning to undergo standard radiation therapy.
  • Performance status KPS 70 or more.
  • SGOT (AST) < 3x upper limit of normal.
  • Serum creatinine < 2mg/dl and calculated creatinine clearance >10ml/min.
  • Platelets > 100,000/mm3 and WBC > 3000/mm3.
  • Patients of reproductive age must agree to use a medically accepted form of birth control while on the study.
  • Must give study specific informed consent prior to enrollment. For re-administration, patients must be re-consented.
  • Must be able to tolerate MRI scan procedure

Exclusion Criteria:

  • Active liver disease including cirrhosis or hepatitis
  • Patients on immunosuppressive drugs (with exception of corticosteroid)
  • Known HIV+ patients.
  • Acute infections (viral, bacterial or fungal infections requiring therapy).
  • Pregnant or breast feeding patients. Female patients of childbearing age must have negative serum or urine pregnancy test within 1 week of beginning therapy.
  • Evidence of metastatic disease or other malignancy (except squamous or basal cell skin cancers).
  • Other serious co-morbid illness or compromised organ function.
  • May not receive chemotherapy until valacyclovir completed
  • May not receive other investigational anti-tumor agents within 30 days prior to study entry or during active participation in the study (defined as from AdV-tk injection until tumor progression).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00589875
Other Study ID Numbers  ICMJE BrTK02
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Advantagene, Inc. d.b.a. Candel Therapeutics
Study Sponsor  ICMJE Advantagene, Inc. d.b.a. Candel Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: E. Antonio Chiocca, MD, PhD Ohio State University
PRS Account Advantagene, Inc. d.b.a. Candel Therapeutics
Verification Date April 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP