Combined Cytotoxic and Immune-Stimulatory Therapy for Glioma
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|ClinicalTrials.gov Identifier: NCT01811992|
Recruitment Status : Completed
First Posted : March 15, 2013
Last Update Posted : August 31, 2021
|Condition or disease||Intervention/treatment||Phase|
|Malignant Glioma Glioblastoma Multiforme||Biological: Dose Escalation of Ad-hCMV-TK and Ad-hCMV-Flt3L||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||19 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Non-randomized, Open-label Dose-finding Trial of Combined Cytotoxic and Immune-Stimulatory Strategy for the Treatment of Resectable Primary Malignant Glioma|
|Actual Study Start Date :||April 2014|
|Actual Primary Completion Date :||February 2019|
|Actual Study Completion Date :||January 2021|
Experimental: Dose escalation of Ad-hCMV-TK and Ad-hCMV-Flt3L
This protocol is a dose escalation study of Ad-hCMV-TK and Ad-hCMV-Flt3L infused at the time of surgical resection followed by systemic oral administration of valacyclovir in addition to current standard of care with temozolomide and radiotherapy. Eligible subjects will be enrolled in six sequential dosing cohorts:
Subjects will be treated sequentially with a minimum of 21 days before treatment of new subjects within a cohort or before dose escalation.
Biological: Dose Escalation of Ad-hCMV-TK and Ad-hCMV-Flt3L
Two adenoviral vectors will be used, each to deliver one of the therapeutic genes. Both vectors are human serotype 5, replication-defective, first generation adenoviral vectors deleted in E1a and E3 viral encoding regions. Each vector will constitutively express their respective therapeutic transgene (i.e. HSV1-TK or Flt3L) under the control of the human cytomegalovirus promoter (hCMV). Valacyclovir treatment will begin 1-3 days after vector administration at a dose of 2 grams given orally 3X per day for 14 days. A second course of valacyclovir will be given beginning Week 10.
Radiation and chemotherapy will be administered as per standard of care.
- Maximum Tolerated Dose (MTD) [ Time Frame: 21 days post administration of study vectors ]Vectors AdhCMV- TK and Ad-hCMV-Flt3L were administered at time of surgery and the MTD determined by dose-limiting toxicities. Toxicities assessed and graded by the NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
- Number of Patients Alive at 12 and 24 Months [ Time Frame: 24 Months ]To assess in a preliminary fashion the potential benefit of AdhCMV- TK and Ad-hCMV-Flt3L treatment of primary malignant gliomas by assessing overall survival (OS) at 12 and 24 months.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01811992
|United States, Michigan|
|University of Michigan Health System Department of Neurosurgery|
|Ann Arbor, Michigan, United States, 48109|
|Principal Investigator:||Pedro Lowenstein, MD, PhD||University of Michigan|