Study Stopped
Sponsor Decision
The Toca 5 Trial: Toca 511 & Toca FC Versus Standard of Care in Patients With Recurrent High Grade Glioma
Toca5
A Phase 2/3 Randomized, Open-Label Study of Toca 511, a Retroviral Replicating Vector, Combined With Toca FC Versus Standard of Care in Subjects Undergoing Planned Resection for Recurrent Glioblastoma or Anaplastic Astrocytoma
2 other identifiers
interventional
403
4 countries
67
Brief Summary
This is a multicenter, randomized, open-label phase 2/3 study of Toca 511 and Toca FC versus standard of care that comprises Investigator's choice of single agent chemotherapy (lomustine or temozolomide) or bevacizumab administered to subjects undergoing resection for first or second recurrence (including this recurrence) of GBM or AA. Subjects meeting all of the inclusion and none of the exclusion criteria will be randomized prior to surgery in a 1:1 ratio to receive either Toca 511 and Toca FC (Experimental arm, Arm T) or control treatment with one option of standard of care (Arm SOC). Stratification will be done by IDH1 mutation status. A second stratification factor is based on the patient's Karnofsky Performance Score (KPS) (70-80 vs 90-100). Further, to account for potential differences in treatment choices for the control arm in regions, the trial will be stratified by geographical region during the randomization process. Funding Source - FDA OOPD
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Nov 2015
Typical duration for phase_2
67 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 3, 2015
CompletedFirst Posted
Study publicly available on registry
April 10, 2015
CompletedStudy Start
First participant enrolled
November 30, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 31, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
December 20, 2019
CompletedFebruary 7, 2020
February 1, 2020
3.5 years
April 3, 2015
February 6, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
To compare the overall survival (OS) of subjects treated with Toca 511 combined with Toca FC to subjects treated according to standard of care after tumor resection for recurrence of glioblastoma or anaplastic astrocytoma
Time from randomization date to death due to any cause
30 December 2019
Secondary Outcomes (4)
Durable Response Rate (CR or PR ≥ 24 weeks)
30 December 2019
Durable Clinical Benefit Rate (CR or PR ≥ 24 weeks or SD ≥ 18 months)
30 December 2019
Duration of Durable Response
30 December 2019
Overall Survival at 12 months
30 December 2019
Study Arms (2)
Toca 511/Toca FC
EXPERIMENTALResection followed by administration of 4 mL Toca 511 (vocimagene amiretrorepvec). Toca 511 is administered by injection into the wall of the subject's tumor resection cavity on Day 1 (approximately 40 injections of 0.1 mL) Toca FC is an extended-release formulation of flucytosine. Toca FC will be administered at 220 mg/kg/day orally for 7-day courses beginning at least 6 weeks after resection and repeated approximately every 6 weeks.
Lomustine, Temozolomide, or Bevacizumab
ACTIVE COMPARATORInvestigator selects one of the following: Bevacizumab: Beginning 6 weeks after tumor resection, bevacizumab will be administered by IV infusion at 10 mg/kg and repeated every 2 weeks. Refer to the prescribing information and to institutional guidelines for details on the administration procedure. Lomustine: Beginning 6 weeks after tumor resection, lomustine will be administered as a single oral dose of 110 mg/m2 and repeated every 6 weeks. Refer to the prescribing information and to institutional guidelines for details regarding the administration procedure. Temozolomide: Beginning 6 weeks after tumor resection, temozolomide will be administered per 1 of 2 options: * at a dose of 50 mg/m2 PO once daily continuously, or * at an initial dose of 150 mg/m2 IV or PO once daily for 5 consecutive days per 28-day treatment cycle that may be raised to 200 mg/ m2 once daily for 5 consecutive days in the following 28-day treatment cycles
Interventions
Toca 511 consists of a purified retroviral replicating vector encoding a modified yeast cytosine deaminase (CD) gene. The CD gene converts the antifungal 5-flurocytosine (5FC) to the anticancer drug 5-FU in cells that have been infected by the Toca 511 vector.
Toca FC is an extended-release formulation of flucytosine and is supplied as 500 mg tablets
Eligibility Criteria
You may qualify if:
- Subject has given written informed consent
- Subject is between 18 years old and 75 years old, inclusive
- Subjects must have histologically proven GBM or AA and:
- Must have received first-line multimodal therapy with surgery followed by temozolomide (unless MGMT promoter unmethylated) and radiation (subjects with GBM must have received temozolomide and radiation concurrently)
- Must be in first or second recurrence (including this recurrence)
- Recurrence must be confirmed by diagnostic biopsy with local pathology review or contrast-enhanced MRI. If first recurrence of GBM is documented by MRI, an interval of at least 12 weeks after the end of prior radiation therapy is required unless there is either: i) histopathologic confirmation of recurrent tumor, or ii) new enhancement on MRI outside of the radiotherapy treatment field
- Subjects must have measurable disease preoperatively, defined as at least 1 contrast-enhancing lesion, with 2 perpendicular measurements of at least 1 cm, as per RANO criteria
- Subjects must be at least 4 weeks post last dose of temozolomide
- Prior gamma knife, stereotactic radiosurgery, or other focal high-dose radiotherapy is allowed but the subject must have either histopathologic confirmation of recurrent tumor, or new enhancement on MRI outside of the radiotherapy treatment field
- Based on the pre-operative evaluation by neurosurgeon, the subject is a candidate for ≥ 80% resection of enhancing region
- IDH mutation status of the primary tumor must be available or tumor samples must be available for pre randomization testing
- Laboratory values adequate for patient to undergo surgery, including:
- Platelet count ≥ 60,000/mm3
- Hgb ≥ 10 g/dL
- Absolute neutrophil count (ANC) ≥ 1,500/mm3
- +8 more criteria
You may not qualify if:
- History of more than 2 prior recurrences (including this recurrence) of GBM or AA
- History of other malignancy, unless the patient has been disease free for at least 5 years. Adequately treated basal cell carcinoma or squamous cell skin cancer is acceptable regardless of time, as well as localized prostate carcinoma or cervical carcinoma in situ after curative treatment
- Histologically confirmed oligodendroglioma or mixed glioma
- Known 1p/19q co deletion
- A contrast enhancing brain tumor that is any of the following:
- Multi focal (defined as 2 separate areas of contrast enhancement measuring at least 1 cm in 2 planes that are not contiguous on either fluid attenuated inversion recovery (FLAIR) or T2 sequences);
- Associated with either diffuse subependymal or leptomeningeal dissemination; or
- \> 5 cm in any dimension
- The subject has or had any active infection requiring systemic antibiotic, antifungal or antiviral therapy within the past 4 weeks
- The subject has any bleeding diathesis, or must take anticoagulants, or antiplatelet agents, including nonsteroidal anti inflammatory drugs (NSAIDs), at the time of the scheduled resection that cannot be stopped for surgery
- The subject is human immunodeficiency virus (HIV) positive
- The subject has a history of allergy or intolerance to flucytosine
- The subject has a gastrointestinal disease that would prevent him or her from being able to swallow or absorb flucytosine
- The subject received cytotoxic chemotherapy within the past 4 weeks (6 weeks for nitrosoureas) of the planned surgery date
- The subject received any investigational treatment within the past 30 days or prior immunotherapy or antibody therapy within the past 45 days.
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Tocagen Inc.lead
Study Sites (67)
Barrow Neurological Institute at Dignity Health St. Joseph's Hospital and Medical Center
Phoenix, Arizona, 85013, United States
University of California, Irvine
Irvine, California, 92868, United States
University of California San Diego
La Jolla, California, 92093, United States
University of California, Los Angeles
Los Angeles, California, 90095, United States
St. Joseph Hospital
Orange, California, 92868, United States
University of California San Francisco
San Francisco, California, 94143, United States
Stanford University
Stanford, California, 94305, United States
University of Colorado Cancer Center
Aurora, Colorado, 80045, United States
Colorado Neurological Institute
Englewood, Colorado, 80113, United States
Associated Neurologists of Southern Connecticut
Fairfield, Connecticut, 06824, United States
Yale University/Yale Cancer Center
New Haven, Connecticut, 06520, United States
University of Florida McKnight Brain Institute
Gainesville, Florida, 32611, United States
University of Miami
Miami, Florida, 33136, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
NorthShore University Health System
Evanston, Illinois, 60201, United States
University of Kansas Medical Center
Kansas City, Kansas, 66160, United States
Johns Hopkins University School of Medicine
Baltimore, Maryland, 21287, United States
University of Michigan
Ann Arbor, Michigan, 48109, United States
Henry Ford Health System
Detroit, Michigan, 48202, United States
Abbott Northwestern Hospital / Allina Health
Minneapolis, Minnesota, 55407, United States
University of Minnesota
Minneapolis, Minnesota, 55455, United States
HCA Midwest / Sarah Cannon
Kansas City, Missouri, 64132, United States
Washington University St. Louis
St Louis, Missouri, 63110, United States
University of Nebraska Medical Center
Omaha, Nebraska, 68198, United States
JFK Medical Center Neuroscience Institute
Edison, New Jersey, 08820, United States
John Theurer Cancer Center at Hackensack University
Hackensack, New Jersey, 07601, United States
Overlook Medical Center
Summit, New Jersey, 07901, United States
North Shore University Hospital
Lake Success, New York, 11042, United States
NYU Langone Medical Center
New York, New York, 10016, United States
Weill Cornell Medical College
New York, New York, 10021, United States
Columbia University
New York, New York, 10032, United States
University of Rochester Medical Center
Rochester, New York, 14642, United States
Stony Brook University Hospital
Stony Brook, New York, 11794, United States
Cincinnati's Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106, United States
Cleveland Clinic
Cleveland, Ohio, 44195, United States
Ohio State University
Columbus, Ohio, 43210, United States
Thomas Jefferson University
Philadelphia, Pennsylvania, 19101, United States
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Sanford Research
Sioux Falls, South Dakota, 57104, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37232, United States
Baylor University Medical Center
Dallas, Texas, 75246, United States
Houston Methodist Hospital Outpatient Center
Houston, Texas, 77030, United States
University of Texas Health Science Center at Houston (UTHealth)
Houston, Texas, 77030, United States
University of Virginia Health System
Charlottesville, Virginia, 22908, United States
Inova Dwight and Martha Schar Cancer Institute
Fairfax, Virginia, 22031, United States
Sentara Neurosurgery Specialists
Norfolk, Virginia, 23507, United States
West Virginia University
Morgantown, West Virginia, 26506, United States
University of Wisconsin
Madison, Wisconsin, 53792, United States
University of Alberta
Edmonton, Alberta, T6G 2B7, Canada
University of British Columbia / Vancouver General Hospital
Vancouver, British Columbia, V5Z 1M9, Canada
CancerCare Manitoba
Winnipeg, Manitoba, R3E 0V9, Canada
London Regional Cancer Centre
London, Ontario, N6A 5W9, Canada
Ottawa Hospital Regional Cancer Centre
Ottawa, Ontario, K1H 8L6, Canada
Sunnybrook Hospital / Sunnybrook Research Institute
Toronto, Ontario, M4N 3M5, Canada
Toronto Western Hospital
Toronto, Ontario, M5T 2S8, Canada
Montreal Neurological Institute
Montreal, Quebec, H3A 2B4, Canada
Jewish General Hospital
Montreal, Quebec, H3T 1E2, Canada
Sherbrooke Hospital University Centre (CHUS)
Sherbrooke, Quebec, J1H 5N4, Canada
Rambam Health Care
Haifa, 3109601, Israel
Hadassah Medical Center
Jerusalem, 91120, Israel
Tel Aviv Sourasky Medical Center
Tel Aviv, 6423906, Israel
Seoul National University Hospital
Seoul, 03080, South Korea
Severance Hospital
Seoul, 03722, South Korea
Samsung Medical Center
Seoul, 06351, South Korea
Seoul St. Mary's Hospital
Seoul, 06591, South Korea
Related Publications (2)
Cloughesy TF, Petrecca K, Walbert T, Butowski N, Salacz M, Perry J, Damek D, Bota D, Bettegowda C, Zhu JJ, Iwamoto F, Placantonakis D, Kim L, Elder B, Kaptain G, Cachia D, Moshel Y, Brem S, Piccioni D, Landolfi J, Chen CC, Gruber H, Rao AR, Hogan D, Accomando W, Ostertag D, Montellano TT, Kheoh T, Kabbinavar F, Vogelbaum MA. Effect of Vocimagene Amiretrorepvec in Combination With Flucytosine vs Standard of Care on Survival Following Tumor Resection in Patients With Recurrent High-Grade Glioma: A Randomized Clinical Trial. JAMA Oncol. 2020 Dec 1;6(12):1939-1946. doi: 10.1001/jamaoncol.2020.3161.
PMID: 33119048DERIVEDCloughesy TF, Landolfi J, Hogan DJ, Bloomfield S, Carter B, Chen CC, Elder JB, Kalkanis SN, Kesari S, Lai A, Lee IY, Liau LM, Mikkelsen T, Nghiemphu PL, Piccioni D, Walbert T, Chu A, Das A, Diago OR, Gammon D, Gruber HE, Hanna M, Jolly DJ, Kasahara N, McCarthy D, Mitchell L, Ostertag D, Robbins JM, Rodriguez-Aguirre M, Vogelbaum MA. Phase 1 trial of vocimagene amiretrorepvec and 5-fluorocytosine for recurrent high-grade glioma. Sci Transl Med. 2016 Jun 1;8(341):341ra75. doi: 10.1126/scitranslmed.aad9784.
PMID: 27252174DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Timothy Cloughesy, MD
University of California, Los Angeles
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 3, 2015
First Posted
April 10, 2015
Study Start
November 30, 2015
Primary Completion
May 31, 2019
Study Completion
December 20, 2019
Last Updated
February 7, 2020
Record last verified: 2020-02