A Phase I Study of AdV-tk + Prodrug Therapy in Combination With Radiation Therapy for Pediatric Brain Tumors - Full Text View

Sponsor:	Dana-Farber Cancer Institute
Collaborators:	Children's Hospital Boston Advantagene, Inc.
Information provided by:	Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:	NCT00634231

Purpose

The primary objectives of this study are to evaluate whether the administration of AdV-tk to malignant brain tumors followed by anti-herpetic prodrug in combination with radiation therapy will be safe, can be effectively delivered without disturbing standard therapy and will have anti-tumor activity in pediatric patients with malignant glioma.

Condition	Intervention	Phase
Childhood Cancer	Drug: Adv-tk Drug: Valacyclovir Radiation: Radiotherapy	Phase I

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase I Study of AdV-tk + Prodrug Therapy in Combination With Radiation Therapy for Pediatric Brain Tumors

Resource links provided by NLM:

Genetics Home Reference related topics: Help Me Understand Genetics

MedlinePlus related topics: Brain Cancer Cancer Childhood Brain Tumors

Drug Information available for: Valaciclovir Valacyclovir hydrochloride

U.S. FDA Resources

Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:

Safety based on standard laboratory and clinical adverse event monitoring [ Time Frame: 14 days of valcyclovir ] [ Designated as safety issue: Yes ]
Immunologic function [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Overall survival [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
Progression-free survival [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
Objective tumor response [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	12
Study Start Date:	April 2010
Estimated Primary Completion Date:	May 2013 (Final data collection date for primary outcome measure)

Intervention Details:

Patients will receive injection of AdV-tk into remaining tumor or tumor bed after resection of malignant glioma.

Two dose levels of AdV-tk will be evaluated:

Level 1 1x1011 vp per injection Level 2 3x1011 vp per injection

Dose escalation will be performed according to the dose escalation and stopping rules in section 7.4 of the protocol with 3-6 patients per dose level.

The prodrug, at a fixed dose, will be started 1-3 days after AdV-tk injection and continue for 14 days.

Other Name: Prodrug

Radiation will be determined and administered as per standard of care for the patient's disease. It will start 3-7 days after AdV-tk injection.

Other Name: Radiation Therapy

Detailed Description:

This is an Open label, Phase I, dose escalation study. Patients will receive injection of AdV-tk into the tumor or tumor bed during a surgical procedure followed by 14 days of prodrug starting 1-3 days after vector injection. Standard radiotherapy will begin 3-7 days after AdV-tK injection. Standard temozolomide chemotherapy may begin after completion of the prodrug at the discretion of the treating physician and family. Two dose levels of AdV-tk will be evaluated with a fixed dose of prodrug.

Eligibility

Ages Eligible for Study:	3 Years to 22 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients must have newly diagnosed supratentorial malignant glioma
Patients must be 3 years of age or older.
Tumor must be accessible for injection and must not be located in the brainstem, deep midbrain, contained within the ventricular system, or located in an infratentorial location.
Patients must be planning to undergo standard radiation therapy.
Performance Score: Karnofsky >60% if >10y/o, Lansky >60% if < 10y/o
Bone Marrow Function: Patients must have adequate bone marrow function defined as a peripheral absolute neutrophil count of > 1000/ µl (unsupported), hemoglobin 8.0 gm/dL (may be supported), and platelet count > 100,000/ µl (unsupported)
Renal Function: Patients must have serum creatinine ≤ 1.5 times upper limit of institutional normal for age and/or GFR 70 mL/min/1.73 m2.
Hepatic Function: Bilirubin x 1.5 times institutional normal; SGPT (ALT) <3x institutional normal for age
Chemistry Function: Normal electrolyte values including sodium, potassium, magnesium, calcium
Patients with seizure disorder may be enrolled if well controlled.

Exclusion Criteria:

Prior or ongoing liver disease including known cirrhosis, hepatitis B or C infection but not to exclude patients with a distant history of resolved hepatitis A infection.
Patients on immunosuppressive drugs (with exception of corticosteroid)
Known history of HIV or underlying immunodeficiency.
Patients with 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.
Prior radiation therapy to the brain or prior treatment for brain tumor except for surgery.
Other serious co-morbid illness or compromised organ function.
No other investigational anti-tumor agents within 30 days prior to study entry or during active participation in the study (defined as from study entry until tumor progression).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00634231

Contacts

Contact: Jessica L Lawlor, BA

617-632-5376

Jessical_lawlor@dfci.harvard.edu

Locations

United States, Massachusetts
Dana-Farber Cancer Institute	Recruiting
Boston, Massachusetts, United States, 02115
Contact: Mark W Kieran, MD, PhD 617-632-4907 mark_kieran@dfci.harvard.edu
Contact: Jay Pietrantonio, BA 617-632-6740 JayB_Pietrantonio@DFCI.HARVARD.EDU
Principal Investigator: Mark W Kieran, MD, PhD

Sponsors and Collaborators

Dana-Farber Cancer Institute

Children's Hospital Boston

Advantagene, Inc.

Investigators

Study Chair:

Mark W Kieran, MD, PhD

Dana-Farber Cancer Institute

More Information

No publications provided

Responsible Party:	Mark W. Kieran MD, PhD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:	NCT00634231 History of Changes
Obsolete Identifiers:	NCT00729105
Other Study ID Numbers:	07-098
Study First Received:	March 5, 2008
Last Updated:	July 6, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:

Supratentorial malignant gliomas
Gene therapy
Immunotherapy

Additional relevant MeSH terms:

Brain Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Brain Diseases
Central Nervous System Diseases

Nervous System Diseases
Valacyclovir
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012