Clinical Trial 18576

Cancer Type:
Interventions:Avastin (Bevacizumab); Bevacizumab; Lomustine (CeeNU); Not Applicable; Temodal (Temozolomide); Temozolomide; Toca 511; Toca FC

Study Type: Treatment
Phase of Study: Phase II/III

  • Nam Tran


Study Title

A Phase 2/3 Randomized, Open-Label Study of Toca 511, a Retroviral Replicating Vector, Combined With Toca FC versus Standard of Care in Subjects Undergoing Planned Resection for Recurrent Glioblastoma or Anaplastic Astrocytoma


The purpose of this study is to: determine if the investigational products, Toca 511 and Toca FC, as a combination treatment is effective (works) and safe, compared to a selected number of approved treatments for brain tumors, called a control treatment.


Primary Objective: To compare the overall survival (OS) of subjects treated with Toca 511 combined with Toca FC to subjects treated according to standard of care after tumor resection for recurrence of glioblastoma or anaplastic astrocytoma. Secondary Objectives: 1. To evaluate the safety of each arm as administered in this study. 2. To assess the objective response rates of each arm. 3. To assess the clinical benefit rate (CR, PR or SD for >= 6 weeks) for each arm. 4. To compare the overall survival (OS) of subjects treated with Toca 511 combined with Toca FC to subjects treated according to standard of care after tumor resection for recurrence of glioblastoma which is IDH wild type. 5. To compare OS at 9, 12, 18 months (OS9, OS12, OS18) between arms. 6. To compare the patient reported outcome and quality of life between arms. 7. To compare progression-free survival (PFS) between arms. 8. To compare PFS at 6 months (PFS-6) between arms.

Inclusion Criteria

  • Have given written informed consent
  • Between 18 years old and 75 years old, inclusive
  • Have histologically proven glioblastoma multiforme (GBM) or anaplastic astrocytoma (AA) in first or second recurrence (including this recurrence) or progression following initial definitive multimodal therapy with surgery, temozolomide (unless O6-methylguanine-DNA methyltransferase (MGMT) promoter unmethylated) and radiation.
  • Have measurable disease preoperatively, defined as at least 1 contrast enhancing lesion, measuring at least 1 cm in 2 planes (axial, coronal, or sagittal)
  • At least 4 weeks post last dose of temozolomide
  • Prior gamma knife, stereotactic radiosurgery, or other focal high-dose radiotherapy is allowed but the subject must have either histopathologic confirmation of recurrent tumor, or new enhancement on MRI outside of the radiotherapy treatment field
  • Based on the pre-operative evaluation by neurosurgeon, is a candidate for >= 80% resection of enhancing region
  • Isocitrate dehydrogenase (IDH) mutation status of the primary tumor must be available or tumor samples must be available for pre randomization testing
  • Laboratory values adequate for patient to undergo surgery
  • Women of childbearing potential must have had a negative serum pregnancy test within the past 21 days and must use a birth control method in addition to barrier methods.
  • Participant or their partner is willing to use condoms for 12 months after receiving Toca 511 or until there is no evidence of the virus in his/her blood, whichever is longer.
  • Has a Karnofsky Performance Score (KPS) >= 70
  • Willing and able to abide by the protocol

  • Exclusion Criteria

  • History of more than 2 prior recurrences (including this recurrence) of GBM or AA
  • 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 acceptable regardless of time, as well as localized prostate carcinoma or cervical carcinoma in situ after curative treatment
  • Histological confirmed oligodendroglioma or mixed glioma
  • Known 1p/19q co-deletion
  • A contrast enhancing brain tumor
  • Has or had any active infection requiring antibiotic, antifungal or antiviral therapy within the past 4 weeks
  • 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 stopped for surgery
  • Is HIV positive
  • Has a history of allergy or intolerance to flucytosine
  • Has a gastrointestinal (GI) disease that would prevent him or her from being able to swallow or absorb flucytosine
  • Received cytotoxic chemotherapy within the past 4 weeks (6 weeks for nitrosoureas) of the planned surgery date
  • Received any investigational treatment within the past 30 days or prior immunotherapy or antibody therapy within the past 45 days.
  • Is breast feeding
  • Intends to undergo treatment with the Gliadel® wafer at the time of this surgery or has received the Gliadel® wafer > Has received bevacizumab for their disease unless in the context of primary therapy for newly diagnosed glioma
  • For potential participants planned to potentially receive bevacizumab, they have no evidence of uncontrolled hypertension (defined as a blood pressure of ≥ 150 mm Hg systolic and/or ≥ 100 mm Hg diastolic on medication) or active GI perforation
  • Has received systemic dexamethasone continuously at a dose > 8 mg/day for 8 weeks prior to the date of the screening assessment
  • Severe pulmonary, cardiac or other systemic disease