A Study of a Retroviral Replicating Vector Combined With a NCT01156584

Clinical Trial Details — Status: Completed

Administrative data
NCT number	NCT01156584
Other study ID #	Tg 511-08-01
Secondary ID
Status	Completed
Phase	Phase 1
First received
Last updated
Start date	July 2010
Est. completion date	August 18, 2016

Study information
Verified date	May 2018
Source	Tocagen Inc.
Contact	n/a
Is FDA regulated	No
Health authority
Study type	Interventional

Clinical Trial 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.

Recruitment information / eligibility
Status	Completed
Enrollment	54
Est. completion date	August 18, 2016
Est. primary completion date	August 18, 2016
Accepts healthy volunteers	No
Gender	All
Age group	18 Years and older
Eligibility	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

Related Conditions & MeSH terms

Intervention

Biological:
• Toca 511 vector
Single, stereotactic, transcranial, intratumoral injection or intravenous injection

Drug:
• 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.

Locations
Country	Name	City	State
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	The Ohio State University	Columbus	Ohio
United States	Henry Ford Hospital	Detroit	Michigan
United States	City of Hope	Duarte	California
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	The Methodist Hospital Research Institute	Houston	Texas
United States	UCLA	Los Angeles	California
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	UCSD	San Diego	California
United States	UCSF	San Francisco	California

Sponsors *(1)*
Lead Sponsor	Collaborator
Tocagen Inc.

Country where clinical trial is conducted

United States,

References & Publications (2)

Ostertag D, Amundson KK, Lopez Espinoza F, Martin B, Buckley T, Galvão da Silva AP, Lin AH, Valenta DT, Perez OD, Ibañez 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. — View Citation

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. — View Citation

Outcome
Type	Measure	Description	Time frame
Primary	Maximum Feasible, Safe and Well Tolerated Dose of Toca 511		8-10 weeks
Secondary	Safety and tolerability of repeated treatment with Toca FC following administration of Toca 511	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)	6 months
Secondary	Overall survival of Subjects		Overall survivial, Overall survivial at 6 months (OS6), 9 months (OS9), and 12 months (OS12)
Secondary	Evaluate progression free survival (PFS) at 6 months		6 months

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Completed	`NCT03018288` - Radiation Therapy Plus Temozolomide and Pembrolizumab With and Without HSPPC-96 in Newly Diagnosed Glioblastoma (GBM)	Phase 2
Withdrawn	`NCT03980249` - Anti-Cancer Effects of Carvedilol With Standard Treatment in Glioblastoma and Response of Peripheral Glioma Circulating Tumor Cells	Early Phase 1
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Terminated	`NCT02905643` - Discerning Pseudoprogression vs True Tumor Growth in GBMs

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

Clinical Trial Details — Status: Completed

Administrative data

Study information

Clinical Trial Summary

Recruitment information / eligibility

Study Design

Related Conditions & MeSH terms

Intervention

Locations

Sponsors (1)

Country where clinical trial is conducted

References & Publications (2)

Outcome

External Links