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

Primary Purpose

Glioblastoma Multiforme, Astrocytoma, Grade III

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
ADV/HSV-tk (gene therapy)
Sponsored by
David Baskin MD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioblastoma Multiforme focused on measuring GBM, glioblastoma, Astrocytoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • All patients must have biopsy proven recurrent anaplastic 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.

    - Patient can receive second treatment of HSV-tk after 6 months

  • 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.
  • 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

Sites / Locations

  • Houston Methodist Neurological InstituteRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ADV/HSV-tk (gene therapy)

Arm Description

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. Patient can receive second treatment of HSV-tk after 6 months

Outcomes

Primary Outcome Measures

Survival in months from Study drug administration (Day 0)
The overall survival in months of recurrent GBM patients drug administration up to five years

Secondary Outcome Measures

Progression Free Survival assessments will be done every 6-8 weeks for 1st year thereafter every 12-14 weeks until disease progression or death
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.

Full Information

First Posted
March 20, 2018
Last Updated
August 30, 2023
Sponsor
David Baskin MD
Collaborators
Center for Cell and Gene Therapy, Baylor College of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT03596086
Brief Title
HSV-tk + Valacyclovir + SBRT + Chemotherapy for Recurrent GBM
Official Title
Phase I-II Study Evaluating HSV-tk + Valacyclovir Gene Therapy Combination With Radiotherapy and Chemotherapy for Recurrent Glioblastoma Multiforme
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 11, 2017 (Actual)
Primary Completion Date
December 30, 2023 (Anticipated)
Study Completion Date
December 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
David Baskin MD
Collaborators
Center for Cell and Gene Therapy, Baylor College of Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma Multiforme, Astrocytoma, Grade III
Keywords
GBM, glioblastoma, Astrocytoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
62 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
ADV/HSV-tk (gene therapy)
Arm Type
Experimental
Arm Description
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. Patient can receive second treatment of HSV-tk after 6 months
Intervention Type
Drug
Intervention Name(s)
ADV/HSV-tk (gene therapy)
Other Intervention Name(s)
gene transfer, gene therapy, HSV-tk
Intervention Description
The investigational adenovirus gene therapy injected at tumor site followed by valacyclovir, radiotherapy, and chemotherapy
Primary Outcome Measure Information:
Title
Survival in months from Study drug administration (Day 0)
Description
The overall survival in months of recurrent GBM patients drug administration up to five years
Time Frame
Up to 60 months as measured in months.
Secondary Outcome Measure Information:
Title
Progression Free Survival assessments will be done every 6-8 weeks for 1st year thereafter every 12-14 weeks until disease progression or death
Description
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.
Time Frame
Up to 60 months as measured in months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: All patients must have biopsy proven recurrent anaplastic astrocytoma or glioblastoma multiforme without evidence of multifocal tumor 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. Patient can receive second treatment of HSV-tk after 6 months 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. Patients with leptomeningeal disease may be considered for enrollment into the study. 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. 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 Patients on immunosuppressive drugs (other than steroids for brain edema). In patients with leptomeningeal disease, no evidence of diffuse disease or spread to the spine. In patients with leptomeningeal disease, no bulky leptomeningeal metastases with potential to obstruct CSF flow will not be enrolled. 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
David S Baskin, MD
Phone
713-441-3803 or 713-201-5792
Email
DBaskin@houstonmethodist.org
First Name & Middle Initial & Last Name or Official Title & Degree
Helga M Jones
Phone
713-363-9388
Email
HMJones@houstonmethodist.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David S Baskin, MD
Organizational Affiliation
Houston Methodist Neurological Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Houston Methodist Neurological Institute
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David S Baskin, MD
Phone
713-441-3800
Email
DBaskin@houstonmethodist.org
First Name & Middle Initial & Last Name & Degree
Helga M Jones
Phone
713-363-9388
Email
HMJones@houstonmethodist.org

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing Plan Description
To be determined

Learn more about this trial

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

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