human stem cell derived neuron
< Back to Clinical Trial List

DB107-RRV, DB107-FC, and Radiation Therapy with or without Temozolomide (TMZ) for High Grade Glioma

Summary

This is a multicenter, open-label study of DB107-RRV (formerly Toca 511) and DB107-FC (formerly Toca FC) when administered following surgical resection in patients with newly diagnosed high grade glioma. The study is designed to evaluate whether treatment with DB107-RRV in combination with DB107-FC when added to standard of care provides clinical benefit to newly diagnosed high-grade glioma when compared to historical performance previously determined in well controlled clinical trials published in the peer reviewed literature.

DB107-RRV is a gene therapy platform designed to selectively infect tumor cells. DB107-FC is an FDA-approved drug known to cross the blood-brain barrier and destroy tumor cells. 

Inclusion Criteria
  1. Subject has provided written informed consent.
  2. Subject is between 18 years of age and 75 years of age, inclusive.
  3. Subject must have a KPS of ≥ 70.
  4. Subjects must have newly diagnosed adult-type diffuse gliomas (World Health Organization Classification 2021) that has not been previously treated with surgery, radiation or chemotherapy (specifically astrocytoma, IDH-mutant or glioblastoma, IDH-wildtype).
  5. Based on the pre-operative evaluation by neurosurgeon, the subject is a candidate for ≥ 80% resection of the enhancing region.
  6. The primary tumor must be made available for central testing for IDH1 mutation, MGMT methylation status.
  7. Willing to provide a blood sample to determine DGM7 status.
  8. Laboratory values adequate for patient to undergo surgery, including:
    1. Platelet count ≥ 60,000/mm3
    2. Hgb ≥ 10 g/dL
    3. Absolute neutrophil count (ANC) ≥ 1,500/mm3
    4. Absolute lymphocyte count ≥ 500/mm3
    5. Adequate liver function, including:
      1. Total bilirubin ≤ 1.5 x ULN (unless patient had Gilbert’s syndrome)
      2. ALT ≤ 2.5 x ULN
    6. Estimated glomerular filtration rate of at least 50mL/min by Cockcroft Gault Formula
  9. Female patients of child-bearing potential and male patients must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for 30-days prior to the first administration of study drug, for the duration of study participation, and for 90-days following completion of the therapy. Should a female patient become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. IF a male patient impregnates a woman or suspects he has impregnated a woman while participating in this study, he should inform his treating physician immediately.
    1. A female of child-bearing potential is any women (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
      1. Has not undergone a hysterectomy or bilateral oophorectomy; or
      2. Has not had ≥ 12 months of non-therapy-induced amenorrhea.
  10. Women must not be breastfeeding.
  11. Subjects must have the ability to understand, and the willingness to comply with the scheduled visits, treatment schedule, laboratory testing and other requirements of the study.

For the most up-to-date criteria, please visit clinicaltrials.gov.

Exclusion Criteria
  1. Prior treatment for HGG.
  2. History of other malignancy unless the patient has been disease-free for at least 5 years. Adequately treated basal cell carcinoma or squamous cell skin cancer is not exclusionary regardless of time, as well as localized prostate carcinoma or cervical carcinoma in situ after curative treatment.
  3. Histological confirmed oligodendroglioma (IDH-mutant and 1p.19q-codeleted) or mixed glioma.
  4. A contrast-enhancing brain tumor that is any of the following:
    1. Multi-focal (defined as 2 separate areas of presumed tumor whether contrast enhancing or not, measuring at least 1cm in 2 planes that are not contiguous;
    2. Associated with either diffuse subependymal or leptomeningeal dissemination; or
    3. > 5cm in any dimension.
  5. The subject has or had an active infection requiring antibiotic, antifungal or antiviral therapy in the 4 weeks preceding study Cycle 1: Day 1.
  6. The subject has any bleeding diathesis, or must take anticoagulants, or antiplatelet agents, including nonsteroidal anti-inflammatory drugs (NSAIDs), at the time of the scheduled resection that cannot be interrupted for surgery.
  7. Subject is HIV positive.
  8. The subject has Hepatitis B (positive test for HBsAg or HBcAb and positive test for HBV-DNA) or Hepatitis C (positive tests for HCV Antibody and HCV-RNA) or Hepatitis B and C co-infection (positive test for ABsAg or HBcAb and positive test for HCV Antibody).
  9. Subject has a history of allergy or intolerance to flucytosine (DB107-FC).
  10. The subject has a gastrointestinal disease that would, in the opinion of the Investigator, prevent him or her from being able to swallow or absorb flucytosine.
  11. The subject intends to undergo treatment with the Gliadel® wafer at the time of resection surgery or has received Gliadel® wafer < 30 days from Cycle 1: Day 1.
  12. Severe pulmonary, cardiac or other systemic disease, which as per Investigator assessment would prevent surgical resection.
  13. Subjects who have any other disease or condition, which as per Investigator assessment may affect the subject’s compliance or place the subject at higher risk of potential treatment complications.

For the most up-to-date trial criteria, please visit clinicaltrials.gov.

 

Investigator(s)

Stay Informed