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

Sponsor

Candel Therapeutics, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT00589875

Collaborator

(none)

Enrollment

Locations

Arm

113.1

Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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).

Condition or Disease	Intervention/Treatment	Phase
Malignant Glioma Glioblastoma Multiforme Anaplastic Astrocytoma	Biological: AdV-tk Drug: Valacyclovir	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

52 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 2a Study of AdV-tk + Valacyclovir Gene Therapy in Combination With Standard Radiation Therapy for Malignant Glioma

Study Start Date :

Mar 1, 2007

Actual Primary Completion Date :

Dec 1, 2015

Actual Study Completion Date :

Aug 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
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.	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 Names: Valtrex

Arm

Intervention/Treatment

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.

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 Names:

Valtrex

Outcome Measures

Primary Outcome Measures

Expand the safety evaluation at the maximum dose of AdV-tk evaluated in a completed phase Ib study [2 months]
Overall survival [5 years]

Secondary Outcome Measures

Progression free survival [24 months]
Quality of life [24 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope Medical Center	Duarte	California	United States	91010
2	The University of Chicago	Chicago	Illinois	United States	60637
3	The Ohio State University Medical Center, Dept. Neurological Surgery	Columbus	Ohio	United States	43210
4	The Methodist Hospital Neurological Institute	Houston	Texas	United States	77030