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

NCT01156584 | Completed Phase 1 DMC

• 1 other identifier: Tg 511-08-01
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 10

Brief Summary

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.

Conditions

Glioblastoma; Anaplastic Astrocytoma; Anaplastic Oligodendroglioma; Anaplastic Oligoastrocytoma

Keywords

glioma; glioblastoma; glioblastoma multiforme; Grade IV astrocytoma; brain cancer; recurrent glioblastoma; GBM; AA; AOD; anaplastic astrocytoma; anaplastic oligodendroglioma; anaplastic oligoastrocytoma; malignant glioma; high grade glioma

Outcome Measures

Primary Outcomes (1)

• Maximum Feasible, Safe and Well Tolerated Dose of Toca 511

  8-10 weeks

Secondary Outcomes (3)

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

  6 months

• Overall survival of Subjects

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

• Evaluate progression free survival (PFS) at 6 months

  6 months

Study Arms (1)

Single arm

EXPERIMENTAL

Toca 511 vector/ Toca FC prodrug

Biological: Toca 511 vector; Drug: Toca FC

Interventions

Toca 511 vector BIOLOGICAL

Single, stereotactic, transcranial, intratumoral injection or intravenous injection

Also known as: Retroviral Replicating Vector (RRV), Gene Therapy, Gene Transfer

Single arm

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.

Also known as: flucytosine, 5-FC, 5-FC XR, Toca FC (extended release flucytosine)

Single arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Tocagen Inc.: lead

Study Sites (10)

City of Hope

Duarte, California, 91010, United States

Location

UCLA

Los Angeles, California, 90095, United States

Location

UCSD

San Diego, California, 92093, United States

Location

UCSF

San Francisco, California, 94143, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232, United States

Location

The Methodist Hospital Research Institute

Houston, Texas, 77030, United States

Location

Related Publications (2)

• Tai CK, Wang WJ, Chen TC, Kasahara N. Single-shot, multicycle suicide gene therapy by replication-competent retrovirus vectors achieves long-term survival benefit in experimental glioma. Mol Ther. 2005 Nov;12(5):842-51. doi: 10.1016/j.ymthe.2005.03.017.

  PMID: 16257382 BACKGROUND

• Ostertag D, Amundson KK, Lopez Espinoza F, Martin B, Buckley T, Galvao da Silva AP, Lin AH, Valenta DT, Perez OD, Ibanez CE, Chen CI, Pettersson PL, Burnett R, Daublebsky V, Hlavaty J, Gunzburg W, Kasahara N, Gruber HE, Jolly DJ, Robbins JM. Brain tumor eradication and prolonged survival from intratumoral conversion of 5-fluorocytosine to 5-fluorouracil using a nonlytic retroviral replicating vector. Neuro Oncol. 2012 Feb;14(2):145-59. doi: 10.1093/neuonc/nor199. Epub 2011 Nov 9.

  PMID: 22070930 BACKGROUND

Related Links

• Website for Accelerate Brain Cancer Cure
• Website for the National Brain Tumor Society

MeSH Terms

Conditions

Glioblastoma; Astrocytoma; Oligodendroglioma; Glioma; Brain Neoplasms

Interventions

Genetic Therapy; Genetic Engineering; Flucytosine

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics; Genetic Techniques; Investigative Techniques; Cytosine; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Asha Das, MD

  Tocagen Inc.

  STUDY DIRECTOR

• Manish Aghi, MD, NS

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2010
• First Posted: July 5, 2010
• Study Start: July 1, 2010
• Primary Completion: August 18, 2016
• Study Completion: August 18, 2016
• Last Updated: May 21, 2018

Record last verified: 2018-05

Locations

US (10)