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

Phase 1

Completed

• Conditions: Glioblastoma; Anaplastic Astrocytoma; Anaplastic Oligodendroglioma; Anaplastic Oligoastrocytoma
• Interventions: Biological: Toca 511 vector; Drug: Toca FC

• Registration Number: NCT01156584
• Lead Sponsor: Tocagen Inc.

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-07
• Study First Submitted: 2010-07-01
• Study First Submitted QC: 2010-07-02
• Study First Posted: 2010-07-05
• Primary Completion: 2016-08-18
• Study Completion: 2016-08-18
• Status Verified: 2018-05
• Last Update Submitted: 2018-05-16
• Last Update Posted: 2018-05-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 54

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Single arm	Toca 511 vector	Toca 511 vector/ Toca FC prodrug
Single arm	Toca FC	Toca 511 vector/ Toca FC prodrug

Primary Outcome Measures

Name	Time	Method
Maximum Feasible, Safe and Well Tolerated Dose of Toca 511	8-10 weeks

Secondary Outcome Measures

Name	Time	Method
Safety and tolerability of repeated treatment with Toca FC following administration of Toca 511	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)
Evaluate progression free survival (PFS) at 6 months	6 months
Overall survival of Subjects	Overall survivial, Overall survivial at 6 months (OS6), 9 months (OS9), and 12 months (OS12)

Trial Locations

Locations (10)

Henry Ford Hospital; 🇺🇸 Detroit, Michigan, United States

UCSD; 🇺🇸 San Diego, California, United States

UCSF; 🇺🇸 San Francisco, California, United States

The Methodist Hospital Research Institute; 🇺🇸 Houston, Texas, United States

Cleveland Clinic Foundation; 🇺🇸 Cleveland, Ohio, United States

University of Pittsburgh Medical Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

City of Hope; 🇺🇸 Duarte, California, United States

UCLA; 🇺🇸 Los Angeles, California, United States

Hackensack University Medical Center; 🇺🇸 Hackensack, New Jersey, United States

The Ohio State University; 🇺🇸 Columbus, Ohio, United States