- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01811992
Combined Cytotoxic and Immune-Stimulatory Therapy for Glioma
A Non-randomized, Open-label Dose-finding Trial of Combined Cytotoxic and Immune-Stimulatory Strategy for the Treatment of Resectable Primary Malignant Glioma
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Michigan
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Ann Arbor, Michigan, United States, 48109
- University of Michigan Health System Department of Neurosurgery
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Newly diagnosed supratentorial brain lesion compatible with a high grade glioma by MR (magnetic resonance) with no prior treatment with either gene therapy, chemotherapy or radiation treatments that is amenable to attempted gross total resection (GTR).Intraoperative histological frozen section at the time of tumor resection should be compatible with high-grade glioma. If intraoperative diagnosis is not high grade glioma, the patient will not be enrolled. "High grade glioma" can include:Glioblastoma multiforme (WHO grade IV); Anaplastic astrocytoma (WHO grade III); Anaplastic oligodendroglioma (WHO grade III); and Anaplastic ependymoma (WHO grade III).
- Karnofsky score ≥70 (Karnofsky scoring system used to quantify general well-being and activities of daily life; scores range from 0 to 100 where 100 represents perfect health and 0 represents death)
- CBC (complete blood count)/differential obtained within 14 days prior, with adequate bone marrow function defined as follows:
- Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3;
- Platelets ≥ 100,000 cells/mm3;
- Hemoglobin ≥ 10.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥10.0 g/dl is acceptable.);
- Adequate renal function, as defined below:
- BUN (blood urea nitrogen) ≤ 30 mg/dl within 14 days prior.
- Creatinine ≤ 1.7 mg/dl within 14 days prior.
- Adequate hepatic function, as defined below:
- Bilirubin ≤ 2.0 mg/dl within 14 days prior.
- ALT (alanine aminotransferase)/AST (aspartate aminotransferase) ≤ 3x laboratory upper limit of normal within 14 days prior.
- Male and female; both genders must use contraception if of reproductive capacity
- Capable of informed consent
- 18-75 years of age
- For women of child bearing age, a negative pregnancy test performed within 14 days of surgery
Exclusion Criteria:
- Diffusely multifocal lesion that is not amenable to GTR (gross total resection)
- Tumors infiltrating the cerebellum, bilateral corpus callosum ("butterfly glioma"), ventricular system, or brain stem
- Infratentorial high grade glioma
- Primary central nervous system (CNS) disease that would interfere with subject evaluation
- Current diagnosis of other cancer except curative cervical cancer in situ, basal or squamous cell carcinoma of the skin.
- Evidence of other significant disease including hematologic, renal or liver disease that is not explained by the patient's current medical condition or concomitant disease, (i.e. levels of absolute neutrophil count (ANC), hemoglobin, platelets, clotting time, serum creatinine, etc). Final decision on inclusion will be made by physician, concerning suitability of patient for surgery.
- HIV, Hepatitis B, Hepatitis
- Active systemic infection
- Immunosuppressive disorders (chronic steroid therapy, acquired or congenital immune deficiency syndromes, autoimmune disease)
- Serious medical conditions (CHF (congestive heart failure), angina, diabetes mellitus, Chronic obstructive pulmonary disease, abnormal bleeding diathesis)
- Any contraindication for undergoing MRI (magnetic resonance imaging)
- Pregnant or lactating females
- Unacceptable anesthesia risk
- Evidence of bleeding diathesis or use of anticoagulant medication or any medication that may increase the risk of bleeding that cannot be stopped prior to surgery.
- Prior gene therapy
- Allergy to valacyclovir or unable to take oral tablets
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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. |
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. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
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21 days post administration of study vectors
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Patients Alive at 12 and 24 Months
Time Frame: 24 Months
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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.
|
24 Months
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Pedro Lowenstein, MD, PhD, University of Michigan
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- UMCC 2015.024
- HUM00057130 (Other Identifier: University of Michigan)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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