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

Primary Purpose

Malignant Glioma, Glioblastoma Multiforme, Anaplastic Astrocytoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
AdV-tk
Valacyclovir
Sponsored by
Candel Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Malignant Glioma focused on measuring Immunotherapy, Cytotoxicity, Tumor vaccine

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

  • City of Hope Medical Center
  • The University of Chicago
  • The Ohio State University Medical Center, Dept. Neurological Surgery
  • The Methodist Hospital Neurological Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Single arm

Arm Description

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.

Outcomes

Primary Outcome Measures

Expand the safety evaluation at the maximum dose of AdV-tk evaluated in a completed phase Ib study
Overall survival

Secondary Outcome Measures

Progression free survival
Quality of life

Full Information

First Posted
December 27, 2007
Last Updated
April 8, 2017
Sponsor
Candel Therapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00589875
Brief Title
Phase 2a Study of AdV-tk With Standard Radiation Therapy for Malignant Glioma (BrTK02)
Acronym
BrTK02
Official Title
A Phase 2a Study of AdV-tk + Valacyclovir Gene Therapy in Combination With Standard Radiation Therapy for Malignant Glioma
Study Type
Interventional

2. Study Status

Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
March 2007 (undefined)
Primary Completion Date
December 2015 (Actual)
Study Completion Date
August 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Candel Therapeutics, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignant Glioma, Glioblastoma Multiforme, Anaplastic Astrocytoma
Keywords
Immunotherapy, Cytotoxicity, Tumor vaccine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
52 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Single arm
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
AdV-tk
Intervention Description
Single dose of 3x10e11 vector particles of AdV-tk delivered to the tumor bed after resection on day 0.
Intervention Type
Drug
Intervention Name(s)
Valacyclovir
Other Intervention Name(s)
Valtrex
Intervention Description
Single course of valacyclovir at dose of 2 grams orally three times per day for 14 days starting on day 1-3
Primary Outcome Measure Information:
Title
Expand the safety evaluation at the maximum dose of AdV-tk evaluated in a completed phase Ib study
Time Frame
2 months
Title
Overall survival
Time Frame
5 years
Secondary Outcome Measure Information:
Title
Progression free survival
Time Frame
24 months
Title
Quality of life
Time Frame
24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
E. Antonio Chiocca, MD, PhD
Organizational Affiliation
Ohio State University
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
The University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
The Ohio State University Medical Center, Dept. Neurological Surgery
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
The Methodist Hospital Neurological Institute
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
26843484
Citation
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.
Results Reference
result

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

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