Clinical Trials /

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

NCT03596086

Description:

Study to assess the safety and efficacy of HSV-tk (gene therapy), valacyclovir, radiotherapy and chemotherapy in recurrent glioblastoma multiforme.

Related Conditions:
  • Anaplastic Astrocytoma
  • Conventional Glioblastoma Multiforme
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: Pro00016414
  • NCT ID: NCT03596086

Conditions

  • Glioblastoma Multiforme
  • Astrocytoma, Grade III

Interventions

DrugSynonymsArms
ADV/HSV-tk (gene therapy)gene transfer, gene therapy, HSV-tkADV/HSV-tk (gene therapy)

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
ADV/HSV-tk (gene therapy)ExperimentalThe 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
  • ADV/HSV-tk (gene therapy)

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Survival in months from Study drug administration (Day 0)
Time Frame:Up to 60 months as measured in months.
Safety Issue:
Description:The overall survival in months of recurrent GBM patients drug administration up to five years

Secondary Outcome Measures

Measure: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
Safety Issue:
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.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:David Baskin MD

Trial Keywords

  • GBM
  • glioblastoma
  • Astrocytoma

Last Updated

September 3, 2020