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

NCT ID: NCT01156584

Last Updated: 2018-05-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-07-31
• Study Completion Date: 2016-08-18

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single arm

Toca 511 vector/ Toca FC prodrug

Group Type: EXPERIMENTAL

Toca 511 vector

Intervention Type: BIOLOGICAL

Single, stereotactic, transcranial, intratumoral injection or intravenous injection

Toca FC

Intervention Type: 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.

Interventions

Toca 511 vector

Single, stereotactic, transcranial, intratumoral injection or intravenous injection

Intervention Type: BIOLOGICAL

Toca FC

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.

Intervention Type: DRUG

Other Intervention Names

Retroviral Replicating Vector (RRV); Gene Therapy; Gene Transfer; flucytosine, 5-FC, 5-FC XR, Toca FC (extended release flucytosine)

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tocagen Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Asha Das, MD

Role: STUDY_DIRECTOR

Tocagen Inc.

Manish Aghi, MD, NS

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

City of Hope

Duarte, California, United States

UCLA

Los Angeles, California, United States

UCSD

San Diego, California, United States

UCSF

San Francisco, California, United States

Henry Ford Hospital

Detroit, Michigan, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

The Ohio State University

Columbus, Ohio, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

The Methodist Hospital Research Institute

Houston, Texas, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 16257382 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22070930 (View on PubMed)

Related Links

http://www.abc2.org

Website for Accelerate Brain Cancer Cure

http://www.braintumor.org

Website for the National Brain Tumor Society

Other Identifiers

Tg 511-08-01

Identifier Type: -

Identifier Source: org_study_id