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HSV-tk + Valacyclovir + SBRT + Chemotherapy for Recurrent GBM

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03596086
Recruitment Status : Recruiting
First Posted : July 23, 2018
Last Update Posted : August 28, 2019
Center for Cell and Gene Therapy, Baylor College of Medicine
Information provided by (Responsible Party):
David Baskin MD, The Methodist Hospital System

Tracking Information
First Submitted Date  ICMJE March 20, 2018
First Posted Date  ICMJE July 23, 2018
Last Update Posted Date August 28, 2019
Actual Study Start Date  ICMJE December 11, 2017
Estimated Primary Completion Date December 30, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 19, 2018)
Survival in months from Study drug administration (Day 0) [ Time Frame: Up to 60 months as measured in months. ]
The overall survival in months of recurrent GBM patients drug administration up to five years
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03596086 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 19, 2018)
Progression Free Survival assessments will be done every 6-8 weeks for 1st year thereafter every 12-14 weeks until disease progression or death [ Time Frame: Up to 60 months as measured in months ]
Patients will have MRI or CT every 6-8 weeks for the first year post surgery. Thereafter patient will have MRI or CT every 12-14 weeks until completion of the protocol study specific treatment. Progression free survival will be assessed by RANO response criteria.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE HSV-tk + Valacyclovir + SBRT + Chemotherapy for Recurrent GBM
Official Title  ICMJE Phase I-II Study Evaluating HSV-tk + Valacyclovir Gene Therapy Combination With Radiotherapy and Chemotherapy for Recurrent Glioblastoma Multiforme
Brief Summary Study to assess the safety and efficacy of HSV-tk (gene therapy), valacyclovir, radiotherapy and chemotherapy in recurrent glioblastoma multiforme.
Detailed Description

This is a prospective phase I-II study to assess the efficacy and toxicity of HSV-tk + valacyclovir gene therapy in combination with radiotherapy in recurrent glioblastoma multiforme or anaplastic astrocytoma. This study is comprised of patients who have failed standard of care treatment (maximal safe resection followed by chemoradiation).

Clinical response will be evaluated by neurological evaluation, neuropsychological testing, and imaging studies as well as by histological examination wherever a re-operation is clinically indicated. Blood samples will be taken for systemic immunological response, blood counts and liver functions tests. Toxicity will be graded by the Common Terminology Criteria for Adverse Events (CTCAE) and Radiation Therapy Oncology Group (RTOG) neuro-toxicity scores. Patients will also be followed to assess median time to progression and median survival.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Glioblastoma Multiforme
  • Astrocytoma, Grade III
Intervention  ICMJE Drug: ADV/HSV-tk (gene therapy)
The investigational adenovirus gene therapy injected at tumor site followed by valacyclovir, radiotherapy, and chemotherapy
Other Names:
  • gene transfer, gene therapy
  • HSV-tk
Study Arms  ICMJE Experimental: ADV/HSV-tk (gene therapy)
The gene therapy investigational product, HSV-tk will be injected during the surgery. Within 24 hours valacyclovir will be given for 14 days. Radiotherapy will be administered over 10 sessions (over 2 weeks) starting within 9 days of surgery. Standard of care/routine chemotherapy will be started concurrent or after completion of the radiotherapy dependent on patient status based on best clinical judgment.
Intervention: Drug: ADV/HSV-tk (gene therapy)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 19, 2018)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 30, 2025
Estimated Primary Completion Date December 30, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • All patients must have biopsy proven recurrent anaplasatic astrocytoma or glioblastoma multiforme without evidence of multifocal tumor or leptomeningeal metastatic disease or brainstem involvement. Multifocal disease does not exist if enhancing areas are connected by abnormal T2 FLAIR on the MRI scan.
  • Radiographic evidence of recurrence/progression by iRANO criteria
  • ≥ 3 weeks since any major surgery, completion of RT, or completion of all prior systemic anticancer therapy (adequately recovered from the acute toxicities of any prior therapy).
  • Life expectancy ≥ 12 weeks.
  • Patients should have the following characteristics: recurrent glioblastoma or AA demonstrated by biopsy or imaging study, ECOG performance status of 0-1, has had prior surgery and radiotherapy /chemotherapy for the glioblastoma.
  • No evidence of other active malignancy (except squamous or basal cell skin cancers).
  • Signed informed consent to participate in the study must be obtained from patients after they have been fully informed of the nature and potential risks of the study by the investigator (or his/her designee) with the aid of written information.
  • Willing to provide biopsies as required by the study.
  • WOCBP must have a negative serum pregnancy test within 7 days prior to the administration of the first study treatment. Women must not be lactating.
  • WOCBP and men must practice an effective method of birth control
  • Patients must have adequate baseline organ function as assessed by the following laboratory values before initiating the protocol:

    • serum creatinine < 1.5 mg/dL
    • T. bilirubin < 2.5 mg/dL, ALT, AST, GGT and AP < 2 x normal
    • Platelet count. > 100,000/ml , ANC> 1500/ml , Hgb> 10 gm/dL
    • Normal partial thromboplastin time (PTT) and Pro-Thrombin Time (PT)
  • Non English speaking patients can participate in this study

Exclusion Criteria

  • Prior treatment with immunomodulatory therapy, immunotherapy, and/or gene vector therapy in the past 3 months.
  • Prior treatment with the HSV-tk vector used in this study
  • Any cytotoxic chemotherapy, RT, or immunotherapy or any investigational drug for this brain tumor within 3 weeks of study treatment start.
  • Evidence of multifocal disease, brainstem involvement, or leptomeningeal metastasis
  • Patients on immunosuppressive drugs (other than steroids for brain edema).
  • Liver disease, such as cirrhosis or active/chronic hepatitis B or C.
  • History of or current alcohol misuse/abuse within the past 12 months.
  • Known or suspected allergy or hypersensitivity to any component of the proposed regimen (gene vector-HSV-tk, Valacyclovir).
  • Inability to swallow food or any condition of the upper gastrointestinal tract that precludes administration of oral medications (Valacyclovir).
  • No active malignancy except for non-melanoma skin cancer or in situ cervical cancer or treated cancer from which the patient has been continuously disease free for more than 5 years.
  • Pregnant or breastfeeding women or women/men able to conceive and unwilling to practice an effective method of birth control. WOCBP must have a negative serum pregnancy test within 7 days prior to the administration of the first study treatment.
  • Presence of active or suspected acute or chronic uncontrolled infection or history of immunocompromise, including a positive HIV test result.
  • Patients < 18 years of age
  • Unwilling or unable to comply with the study protocol.
  • The presence of active CNS toxoplasmosis infection or Progressive Multifocal Leukoencephalopathy demonstrated on CT or MRI imaging.
  • The presence of active untreated cellulitis or untreated wound infections. Treated and resolving cellulitis and infections are not an exclusion criteria.
  • Active IV drug abuse or severe opioid abuse
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: David S Baskin, MD 713-441-3803 or 713-201-5792
Contact: Helga M Jones 713-363-9388
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT03596086
Other Study ID Numbers  ICMJE Pro00016414
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Plan Description: To be determined
Responsible Party David Baskin MD, The Methodist Hospital System
Study Sponsor  ICMJE David Baskin MD
Collaborators  ICMJE Center for Cell and Gene Therapy, Baylor College of Medicine
Investigators  ICMJE
Principal Investigator: David S Baskin, MD Houston Methodist Neurological Institute
PRS Account The Methodist Hospital System
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP