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Completed

NCT Number: NCT01156584

A Study of a Retroviral Replicating Vector Combined With a Prodrug Administered to Patients With Recurrent Malignant Glioma

This is a multicenter, open-label, ascending-dose trial of the safety and tolerability of increasing doses of Toca 511, a Retroviral Replicating Vector (RRV), administered to patients with recurrent high grade glioma (rHGG) who have undergone surgery followed by adjuvant radiation therapy and chemotherapy. Patients will receive Toca 511 either via stereotactic, transcranial injection into their tumor or as an intravenous injection given daily for 3 & 5 days, depending on cohort. Approximately 3-4 weeks following injection of the RRV, treatment with Toca FC, an antifungal agent, will commence and will be repeated approximately every 6 weeks until study completion. After completion of this study, all patients will be eligible for enrollment and encouraged to enter a long-term continuation protocol that enables additional Toca FC treatment cycles to be given, as well as permits the collection of long-term safety and survival data.

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Key information

Conditions

Glioblastoma Anaplastic Astrocytoma Anaplastic Oligoastrocytoma Anaplastic Oligodendroglioma Astrocytoma Brain Diseases Brain Neoplasms Central Nervous System Diseases Central Nervous System Neoplasms Glioma Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neoplasms, Neuroepithelial Nervous System Diseases Nervous System Neoplasms Neuroectodermal Tumors Oligodendroglioma

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

City of Hope, Duarte, California, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • at least 18 years of age
  • for intratumoral cohorts, supratentorial HGG (WHO grade III or IV)
  • technically unresectable HGG
  • initial definitive therapy such as surgery with or without adjuvant radiation
  • subject elected not to undergo treatment with Gliadel wafer
  • if receiving corticosteroids, dose is stable or decreasing for past 7 days
  • KPS: at least 70
  • absolute neutrophil count > 1500/mm^3
  • absolute lymphocyte count > 500/mm^3
  • platelet count > 100,000/mm^3
  • hemoglobin > 10 g/dL
  • for intratumoral cohort, coagulation profile favorable to surgery
  • estimated glomerular filtration rate > 50 mL/min
  • ALT < 3 times ULN and bilirubin < 1.5 mg/dL
  • negative serum pregnancy test

Exclusion criteria

  • cytotoxic therapy within the past 4 weeks (6 weeks for BCNU/CCNU)
  • more than 2 recurrences including present recurrence
  • Gliadel wafer or wafers implanted within the past 8 weeks
  • taking more than 8 mg of dexamethasone per day
  • for intratumoral cohorts, injection of tumor would require violation of ventricular system
  • any infection requiring antibiotic, anticoagulant, or antiplatelet agents within the past 4 weeks
  • for intratumoral cohort, bleeding diathesis or use of anticoagulants/antiplatelet agents that cannot be stopped
  • allergy or intolerance to 5-FC
  • HIV positive
  • g.i. condition that would prevent ingestion or absorption of 5-FC
  • any investigational treatment within the past 30 days
  • pregnant or breast feeding
  • received Avastin
  • history of prior malignancy, excluding basal or squamous cell carcinoma of the skin, with an expected survival of less than 5 years.

Treatment and study plan

Toca 511 vector

Biological

Single, stereotactic, transcranial, intratumoral injection or intravenous injection

Other names: Retroviral Replicating Vector (RRV), Gene Therapy, Gene Transfer

Toca FC

Drug

4-6 week cycles of Toca FC. Doses evaluated from 120 mg/kg/day or 300 mg/kg/day. Duration of dosing evaluated: 6 days, 7 days or 14 days.

Other names: flucytosine, 5-FC, 5-FC XR, Toca FC (extended release flucytosine)

Primary outcomes

  1. Maximum Feasible, Safe and Well Tolerated Dose of Toca 511

    Time frame: 8-10 weeks

Secondary outcomes

  1. Safety and tolerability of repeated treatment with Toca FC following administration of Toca 511

    Time frame: 6 months

    Review of adverse events including laboratory safety data (specifically any Grade 3 or higher non-hematologic toxicity or any Grade 4 or higher hematologic toxicity, felt to be related to Toca 511 or the Toca 511/Toca FC combination)

  2. Overall survival of Subjects

    Time frame: Overall survivial, Overall survivial at 6 months (OS6), 9 months (OS9), and 12 months (OS12)

  3. Evaluate progression free survival (PFS) at 6 months

    Time frame: 6 months

Sponsors and collaborators

Lead sponsor

Tocagen Inc.

Industry

Registry information

Official study title

A Phase 1 Ascending Dose Trial of the Safety and Tolerability of Toca 511 in Patients With Recurrent High Grade Glioma

Important dates

Study start
2010
Primary completion
2016
Study completion
2016
First posted
Jul 5, 2010
Registry last updated
May 21, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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