RECRUITING

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

Conditions

Glioblastoma Multiforme Astrocytoma, Grade III GBM glioblastoma Astrocytoma

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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

Official Title

Phase I-II Study Evaluating HSV-tk + Valacyclovir Gene Therapy Combination with Radiotherapy and Chemotherapy for Recurrent Glioblastoma Multiforme

Quick Facts

Study Start:2017-12-11

Study Completion:2025-12-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT03596086

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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 * 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	Pregnancy or breastfeeding Severe psychiatric disorders Active substance abuse Unstable medical conditions Inability to comply with study requirements

Inclusion Criteria

Exclusion 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
* 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

Pregnancy or breastfeeding
Severe psychiatric disorders
Active substance abuse
Unstable medical conditions
Inability to comply with study requirements

Contacts and Locations

Study Contact

David S Baskin, MD

CONTACT

713-441-3803 or 713-201-5792

DBaskin@houstonmethodist.org

Helga M Jones

CONTACT

713-363-9388

HMJones@houstonmethodist.org

Principal Investigator

David S Baskin, MD

PRINCIPAL_INVESTIGATOR

Houston Methodist Neurological Institute

Study Locations (Sites)

Houston Methodist Neurological Institute

Houston, Texas, 77030

United States

Collaborators and Investigators

Sponsor: David Baskin MD

David S Baskin, MD, PRINCIPAL_INVESTIGATOR, Houston Methodist Neurological Institute

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2017-12-11

Study Completion Date2025-12-30

Study Record Updates

Study Start Date2017-12-11

Study Completion Date2025-12-30

Terms related to this study

Keywords Provided by Researchers

GBM
glioblastoma
Astrocytoma

Additional Relevant MeSH Terms

Glioblastoma Multiforme
Astrocytoma, Grade III