The Toca 5 Trial: Toca 511 & Toca FC Versus Standard of Care in Patients With Recurrent High Grade Glioma
NCT ID: NCT02414165
Last Updated: 2020-02-07
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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TERMINATED
PHASE2/PHASE3
403 participants
INTERVENTIONAL
2015-11-30
2019-12-20
Brief Summary
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Funding Source - FDA OOPD
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Toca 511/Toca FC
Resection 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.
Toca 511
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
Toca FC is an extended-release formulation of flucytosine and is supplied as 500 mg tablets
Lomustine, Temozolomide, or Bevacizumab
Investigator 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
Lomustine
Temozolomide
Bevacizumab
Interventions
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Toca 511
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
Toca FC is an extended-release formulation of flucytosine and is supplied as 500 mg tablets
Lomustine
Temozolomide
Bevacizumab
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Subject is between 18 years old and 75 years old, inclusive
3. Subjects must have histologically proven GBM or AA and:
1. 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)
2. Must be in first or second recurrence (including this recurrence)
3. 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
4. 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
5. Subjects must be at least 4 weeks post last dose of temozolomide
6. 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
7. Based on the pre-operative evaluation by neurosurgeon, the subject is a candidate for ≥ 80% resection of enhancing region
8. IDH mutation status of the primary tumor must be available or tumor samples must be available for pre randomization testing
9. 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
* Absolute lymphocyte count (ALC) ≥ 500/mm3
* Adequate liver function, including:
* Total bilirubin ≤ 1.5 x ULN (unless has Gilbert's syndrome)
* ALT ≤ 2.5 x ULN f. Estimated glomerular filtration rate of at least 50 mL/min by the Cockcroft Gault formula
10. Women of childbearing potential (≥12 months of non-therapy-induced amenorrhea or surgically sterile) must have had a negative serum pregnancy test within the past 21 days and must use a birth control method in addition to barrier methods (condoms).
11. Subject or subject's partner is willing to use condoms for 12 months after receiving Toca 511 or until there is no evidence of the virus in his/her blood, whichever is longer.
12. The subject has a KPS ≥ 70
13. The subject is willing and able to abide by the protocol
Exclusion Criteria
2. 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
3. Histologically confirmed oligodendroglioma or mixed glioma
4. Known 1p/19q co deletion
5. 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
6. The subject has or had any active infection requiring systemic antibiotic, antifungal or antiviral therapy within the past 4 weeks
7. 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
8. The subject is human immunodeficiency virus (HIV) positive
9. The subject has a history of allergy or intolerance to flucytosine
10. The subject has a gastrointestinal disease that would prevent him or her from being able to swallow or absorb flucytosine
11. The subject received cytotoxic chemotherapy within the past 4 weeks (6 weeks for nitrosoureas) of the planned surgery date
12. The subject received any investigational treatment within the past 30 days or prior immunotherapy or antibody therapy within the past 45 days.
13. The subject is pregnant or breast feeding
14. The subject intends to undergo treatment with the Gliadel® wafer at the time of this surgery or has received the Gliadel® wafer \< 30 days from W1D1 (surgery)
15. The subject has received bevacizumab for their disease unless in the context of primary therapy for newly diagnosed glioma
16. For subjects planned to potentially receive bevacizumab, they have no evidence of uncontrolled hypertension (defined as a blood pressure of ≥ 150 mm Hg systolic and/or ≥ 100 mm Hg diastolic on medication) or active GI perforation
17. The subject has received systemic dexamethasone continuously at a dose \> 8 mg/day for 8 weeks prior to the date of the screening assessment
18. Severe pulmonary, cardiac or other systemic disease, specifically:
* New York Heart Association \> Grade 2 congestive heart failure within 6 months prior to study entry, unless asymptomatic and well controlled with medication
* Uncontrolled or significant cardiovascular disease, clinically significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation, or Torsades des pointes), clinically significant pulmonary disease (such as ≥ Grade 2 dyspnea, according to CTCAE 4.03)
* Subjects who have any other disease, either metabolic or psychological, which as per Investigator assessment may affect the subject's compliance or place the subject at higher risk of potential treatment complications
18 Years
75 Years
ALL
No
Sponsors
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Tocagen Inc.
INDUSTRY
Responsible Party
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Principal Investigators
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Timothy Cloughesy, MD
Role: PRINCIPAL_INVESTIGATOR
University of California, Los Angeles
Locations
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Barrow Neurological Institute at Dignity Health St. Joseph's Hospital and Medical Center
Phoenix, Arizona, United States
University of California, Irvine
Irvine, California, United States
University of California San Diego
La Jolla, California, United States
University of California, Los Angeles
Los Angeles, California, United States
St. Joseph Hospital
Orange, California, United States
University of California San Francisco
San Francisco, California, United States
Stanford University
Stanford, California, United States
University of Colorado Cancer Center
Aurora, Colorado, United States
Colorado Neurological Institute
Englewood, Colorado, United States
Associated Neurologists of Southern Connecticut
Fairfield, Connecticut, United States
Yale University/Yale Cancer Center
New Haven, Connecticut, United States
University of Florida McKnight Brain Institute
Gainesville, Florida, United States
University of Miami
Miami, Florida, United States
Moffitt Cancer Center
Tampa, Florida, United States
NorthShore University Health System
Evanston, Illinois, United States
University of Kansas Medical Center
Kansas City, Kansas, United States
Johns Hopkins University School of Medicine
Baltimore, Maryland, United States
University of Michigan
Ann Arbor, Michigan, United States
Henry Ford Health System
Detroit, Michigan, United States
Abbott Northwestern Hospital / Allina Health
Minneapolis, Minnesota, United States
University of Minnesota
Minneapolis, Minnesota, United States
HCA Midwest / Sarah Cannon
Kansas City, Missouri, United States
Washington University St. Louis
St Louis, Missouri, United States
University of Nebraska Medical Center
Omaha, Nebraska, United States
JFK Medical Center Neuroscience Institute
Edison, New Jersey, United States
John Theurer Cancer Center at Hackensack University
Hackensack, New Jersey, United States
Overlook Medical Center
Summit, New Jersey, United States
North Shore University Hospital
Lake Success, New York, United States
NYU Langone Medical Center
New York, New York, United States
Weill Cornell Medical College
New York, New York, United States
Columbia University
New York, New York, United States
University of Rochester Medical Center
Rochester, New York, United States
Stony Brook University Hospital
Stony Brook, New York, United States
Cincinnati's Children's Hospital Medical Center
Cincinnati, Ohio, United States
University Hospitals Cleveland Medical Center
Cleveland, Ohio, United States
Cleveland Clinic
Cleveland, Ohio, United States
Ohio State University
Columbus, Ohio, United States
Thomas Jefferson University
Philadelphia, Pennsylvania, United States
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States
Medical University of South Carolina
Charleston, South Carolina, United States
Sanford Research
Sioux Falls, South Dakota, United States
Vanderbilt University Medical Center
Nashville, Tennessee, United States
Baylor University Medical Center
Dallas, Texas, United States
Houston Methodist Hospital Outpatient Center
Houston, Texas, United States
University of Texas Health Science Center at Houston (UTHealth)
Houston, Texas, United States
University of Virginia Health System
Charlottesville, Virginia, United States
Inova Dwight and Martha Schar Cancer Institute
Fairfax, Virginia, United States
Sentara Neurosurgery Specialists
Norfolk, Virginia, United States
West Virginia University
Morgantown, West Virginia, United States
University of Wisconsin
Madison, Wisconsin, United States
University of Alberta
Edmonton, Alberta, Canada
University of British Columbia / Vancouver General Hospital
Vancouver, British Columbia, Canada
CancerCare Manitoba
Winnipeg, Manitoba, Canada
London Regional Cancer Centre
London, Ontario, Canada
Ottawa Hospital Regional Cancer Centre
Ottawa, Ontario, Canada
Sunnybrook Hospital / Sunnybrook Research Institute
Toronto, Ontario, Canada
Toronto Western Hospital
Toronto, Ontario, Canada
Montreal Neurological Institute
Montreal, Quebec, Canada
Jewish General Hospital
Montreal, Quebec, Canada
Sherbrooke Hospital University Centre (CHUS)
Sherbrooke, Quebec, Canada
Rambam Health Care
Haifa, , Israel
Hadassah Medical Center
Jerusalem, , Israel
Tel Aviv Sourasky Medical Center
Tel Aviv, , Israel
Seoul National University Hospital
Seoul, , South Korea
Severance Hospital
Seoul, , South Korea
Samsung Medical Center
Seoul, , South Korea
Seoul St. Mary's Hospital
Seoul, , South Korea
Countries
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References
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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.
Cloughesy 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.
Other Identifiers
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FD-R-5732
Identifier Type: OTHER_GRANT
Identifier Source: secondary_id
Tg 511-15-01
Identifier Type: -
Identifier Source: org_study_id
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