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HSV-tk and XRT and Chemotherapy for Newly Diagnosed GBM

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ClinicalTrials.gov Identifier: NCT03603405
Recruitment Status : Recruiting
First Posted : July 27, 2018
Last Update Posted : August 26, 2019
Sponsor:
Information provided by (Responsible Party):
David Baskin MD, The Methodist Hospital System

Brief Summary:
Study to assess the safety and efficacy of HSV-tk (gene therapy), valacyclovir, radiotherapy and chemotherapy in newly diagnosed glioblastoma multiforme (GBM) or anaplastic astrocytoma (AA).

Condition or disease Intervention/treatment Phase
Glioblastoma Anaplastic Astrocytoma Drug: ADV/HSV-tk (gene therapy) Phase 1 Phase 2

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 and standard of care chemotherapy for anaplastic astrocytoma (AA) or glioblastoma multiforme (GBM). This study is comprised of newly diagnosed patients with AA or GBM.

Clinical response will be evaluated by neurological evaluation, neuropsychological testing, and imaging studies as well as by histological examination. Blood samples will be taken for systemic immunological response, blood counts, and liver functions tests. Genetic testing of tumor tissue will be performed, including genetic analysis and cell cultures. Toxicity will be graded by the Common Terminology Criteria for Adverse Events (CTCAE) v4.03 and Radiation Therapy Oncology Group (RTOG) neuro-toxicity scores (see Appendices). Patients will also be followed to assess median time to progression and median survival.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 62 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I-II Study Evaluating HSV-tK + VALACYCLOVIR GENE THERAPY Combination With Radiotherapy and Chemotherapy for Newly Diagnosed Anaplastic Astrocytoma and Glioblastoma Multiforme.
Actual Study Start Date : February 28, 2018
Estimated Primary Completion Date : December 31, 2023
Estimated Study Completion Date : December 31, 2025


Arm Intervention/treatment
Experimental: Experimental: ADV/HSV-tk (gene therapy)

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 30 sessions (over 6 weeks) starting within 9 days of surgery. Standard of care/routine chemotherapy will be started concurrent with the radiotherapy dependent on patient status based on best clinical judgment following the Stupp protocol.

Drug: ADV/HSV-tk (gene therapy)
The investigational adenovirus gene therapy injected at tumor site followed by valacyclovir, radiotherapy, and chemotherapy
Other Names:
  • gene therapy, gene therapy
  • HSV-tk




Primary Outcome Measures :
  1. Overall Survival in months up to 5 years from Study drug administration (Day 0) [ Time Frame: Up to 60 months measured in months ]
    The overall survival rate of patients with Anaplastic Astrocytoma and Glioblastoma in months will be assessed up to 5 years from study drug administration.


Secondary Outcome Measures :
  1. 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 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • All patients must have frozen section biopsy proven anaplastic astrocytoma or glioblastoma multiforme without evidence of multifocal tumor or leptomeningeal metastatic disease or brainstem involvement as well as radiographic evidence consistent with these diagnoses.
  • Life expectancy ≥ 12 weeks.
  • Patients should have the following characteristics: newly diagnosed anaplastic astrocytoma or glioblastoma demonstrated by frozen section biopsy, ECOG performance status of 0-1. 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 Alk Phos < 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)

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 within 3 weeks of study treatment start.
  • Evidence of multifocal disease, brainstem involvement, or leptomeningeal metastasis, Discrete areas of contrast enhancement connected by abnormal T2 FLAIR signal on MRI scan are not considered multifocal disease, as this represents a single tumor.
  • 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/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 3 years.
  • 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
  • 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.

Information from the National Library of Medicine

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): NCT03603405


Contacts
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Contact: David S. Baskin, MD 713-441-3803 or 713-201-5792 DBaskin@houstonmethodist.org
Contact: Helga M. Jones 713-363-9388 HMJones@houstonmethodist.org

Locations
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United States, Texas
Houston Methodist Neurological Institute Recruiting
Houston, Texas, United States, 77030
Contact: David S. Baskin, MD    713-441-3800    DBaskin@houstonmethodist.org   
Contact: Helga M. Jones    713-363-9388    HMJones@houstonmethodist.org   
Sponsors and Collaborators
The Methodist Hospital System
Investigators
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Principal Investigator: David S. Baskin, MD Houston Methodist Neurological Institute

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Responsible Party: David Baskin MD, Sponsor-Investigator and Principal Investigator, The Methodist Hospital System
ClinicalTrials.gov Identifier: NCT03603405     History of Changes
Other Study ID Numbers: Pro00018178
First Posted: July 27, 2018    Key Record Dates
Last Update Posted: August 26, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: To be determined

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by David Baskin MD, The Methodist Hospital System:
GBM, AA, Glioblastoma, Astrocytoma
Additional relevant MeSH terms:
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Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Valacyclovir
Antiviral Agents
Anti-Infective Agents