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A Study of Toca 511, a Retroviral Replicating Vector, Combined With Toca FC in Patients With Solid Tumors or Lymphoma (Toca 6)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02576665
Recruitment Status : Terminated (Sponsor decision)
First Posted : October 15, 2015
Last Update Posted : February 7, 2020
Information provided by (Responsible Party):
Tocagen Inc.

Tracking Information
First Submitted Date  ICMJE October 12, 2015
First Posted Date  ICMJE October 15, 2015
Last Update Posted Date February 7, 2020
Actual Study Start Date  ICMJE July 2016
Actual Primary Completion Date May 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 5, 2017)
Changes from baseline in immune activity in tumor and peripheral blood [ Time Frame: Baseline to Weeks 9-10 ]
Original Primary Outcome Measures  ICMJE
 (submitted: October 13, 2015)
Number of patients with vector deposition detected in the resected tumor specimens following administration of Toca 511 [ Time Frame: Assessment of virus deposition 6 months after FPFV ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: October 13, 2015)
  • Number of patients who received Toca 511 and Toca FC with treatment related adverse events as assessed by CTCAE v4.0 [ Time Frame: Assessment of safety 6 months after FPFV ]
  • Number of surviving patients who do not have documented tumor progression following treatment [ Time Frame: Evaluate response 2 years after FPFV ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE A Study of Toca 511, a Retroviral Replicating Vector, Combined With Toca FC in Patients With Solid Tumors or Lymphoma (Toca 6)
Official Title  ICMJE A Phase 1b Study of Toca 511, a Retroviral Replicating Vector, Combined With Toca FC in Patients With Solid Tumors or Lymphoma
Brief Summary

The purpose of this trial is to evaluate changes in immune activity relative to baseline following treatment with Toca 511 and Toca FC in patients with solid tumors (including recurrent high grade glioma [rHGG]) or lymphoma. This is a multicenter, open-label study of Toca 511 and Toca FC. Patients with advanced solid tumors or lymphoma, for whom curative options are not available, will be enrolled into the study, subject to all entry criteria. Tumors must be accessible to biopsy and/or resection. Patients will be qualified based on the presence of specific molecular characteristics, documented by Foundation Medicine (or equivalent) genomic profile report, and specific tumor types.

Toca 511 will be administered by IV injection followed by (1) intratumoral injection following biopsy or (2) injection into the resection cavity wall following planned resection in the case of rHGG or brain metastases. Toca FC will be administered orally in cycles of therapy.

Patients not undergoing resection of brain tumors will undergo 2 biopsies to allow assessment of baseline and follow-up immune activity in the tumor. Changes in immune activity in peripheral blood will be measured in all patients.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Colorectal Cancer
  • Triple Negative Breast Cancer
  • Pancreatic Cancer
  • Non-Small Cell Lung Cancer
  • Head and Neck Cancer
  • Ovarian Cancer
  • Lymphoma
  • Sarcoma
  • Bladder Cancer
  • Melanoma
  • IDH1 Mutated Solid Tumors
  • IDH1 Mutated or MGMT Methylated Recurrent HGG (Not Recruiting)
Intervention  ICMJE
  • Biological: 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-fluorocytosine (5FC) to the anticancer drug 5-FU in cells that have been infected by the Toca 511 vector
    Other Names:
    • vocimagene amiretrorepvec
    • RRV
    • retroviral replicating viral
  • Drug: Toca FC
    Toca FC is an extended-release formulation of flucytosine. Toca FC is supplied as 500 mg white, oblong tablets with "TOCA FC" embossed on one side and "500" embossed on the other side
    Other Names:
    • Flucytosine
    • 5-FC
    • 5-Fluorocytosine
Study Arms  ICMJE Experimental: Toca 511/Toca FC

Toca 511: 14 mL intravenously daily for 3 days followed by up to 4 mL intratumorally or into resection cavity walls following biopsy or resection. Cutaneous melanoma patients may receive intralesional injections (up to 4 mL) daily for 5 days.

Toca FC: 220 mg/kg/day orally starting at Week 5-6. Cycles are 5- to 7- day courses of treatment every 4 to 6 weeks.

  • Biological: Toca 511
  • Drug: Toca FC
Publications *

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: January 3, 2020)
Original Estimated Enrollment  ICMJE
 (submitted: October 13, 2015)
Actual Study Completion Date  ICMJE December 20, 2019
Actual Primary Completion Date May 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Patient has given written informed consent.
  2. Patient is between 18 and 75 years of age, inclusive.
  3. Patient has an advanced malignancy that has progressed or recurred following standard therapy for advanced disease, and for which no curative therapies are available.
  4. Patient has histologically confirmed (1) colorectal cancer, triple negative breast cancer, pancreatic cancer, non-small cell lung cancer, head and neck cancer, ovarian cancer, lymphoma, sarcoma, bladder cancer, or melanoma with defects in one or more of the following genes: ABL2, ACVR1B, APC, ASXL1, ATM, ATR, BLM, BRCA1, BRCA2, CDK12, CDKN1A, CDKN1B, CDKN2A, CHD4, CYLD, DICER1, DNMT3A, ERBB3, EZH2, FGFR2, FLT3, GATA3, HGF, KDM6A, KDR, KEAP1, KIT, KMT2D, KRAS, MAGI2, MAP3K1, MED12, MET, MSH-2, MSH-6, MYC, NA, NF1, NF2, NOTCH1, NOTCH2, NRAS, NSD1, PIK3C2B, PIK3CA, PIK3CB, PIK3R1, PTCH1, PTPN11, RB1, RUNX1, SETD2, SMARCA4, SOX9, STAG2, TAF1, TBX3, TET2, TP53, XPO1; (2) documented IDH1 mutated solid tumor (other than glioma); or (3) documented IDH1 mutated or MGMT promoter methylation positive glioblastoma multiforme (GBM) or anaplastic astrocytoma. Note: Genetic abnormalities must be documented by Foundation Medicine (or equivalent) genomic profile report.
  5. Patient has an estimated life expectancy of at least 6 months.
  6. Patient has adequate organ function, as indicated by the following laboratory values

    • Bone marrow: hemoglobin ≥ 10 g/dL, platelet count ≥ 100,000/mm3, absolute neutrophil count ≥ 1,500/ mm3, absolute lymphocyte count ≥ 500/ mm3.
    • Liver: total bilirubin ≤ 1.5 x the upper limit of normal (ULN; unless known Gilbert's syndrome); alanine aminotransferase ≤ 2.5 x ULN (≤ 5.0 x ULN in patients with liver metastases).
    • Kidney: estimated glomerular filtration rate (Cockcroft-Gault) ≥ 50 mL/min.
  7. Women of childbearing potential (defined as not postmenopausal [ie, ≥ 12 months of non-therapy-induced amenorrhea] or not surgically sterile) must have a negative serum pregnancy test within 21 days prior to initiation of Toca 511, and be willing to use an effective means of contraception in addition to barrier methods (condoms).
  8. Patient and partner are 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.
  9. Patients with solid tumors or lymphoma must have 1 or more tumors accessible to biopsy or resection, including biopsy allowing multiple cores from at least 1 lesion (fine needle aspiration is excluded), incisional or excisional biopsy, and/or resection. Note: Patients with resectable brain metastases must be undergoing planned resection. Patients with rHGG must be undergoing planned subtotal or gross total resection.
  10. Patient has a tumor amenable to injection of Toca 511 (ie, ≥ 2 cm and not close to or invading major vessels).
  11. Patient has an ECOG Performance Status score of 0 or 1 (solid tumors) or KPS score ≥ 70 (rHGG).
  12. Patient has measurable disease by RECIST version 1.1 (solid tumors) or Lugano (lymphoma) criteria or evaluable or measureable disease by Macdonald criteria (rHGG).
  13. Patients with GBM or anaplastic astrocytoma must be at first or second recurrence (including this recurrence) or have progressed following initial definitive multimodal therapy with surgery, temozolomide, and radiation (confirmed by diagnostic biopsy with local pathology review or contrast-enhanced magnetic resonance imaging [MRI]). If first recurrence is documented by MRI, an interval of at least 12 weeks after the end of prior radiation therapy is required, unless there is either histopathologic confirmation of recurrent tumor or new enhancement on MRI outside the radiotherapy treatment field.

Exclusion Criteria:

  1. Patient has a 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.
  2. Patient has or had any active infection requiring antibiotic, antifungal, or antiviral therapy within the 2 weeks prior to administration of Toca 511.
  3. Patient received chemotherapy within 2 weeks prior to initiation of treatment with Toca 511 (6 weeks for nitrosoureas).
  4. Patient received investigational treatment within 2 weeks or immunotherapy or antibody therapy within 28 days prior to initiation of treatment with Toca 511, and/or has not recovered from toxicities associated with such treatment.
  5. For patients with rHGG, the patient intends to undergo treatment with the Gliadel® wafer at the time of planned resection (ie, on-study surgery) or has received the Gliadel wafer < 30 days from the date of planned resection.
  6. Patient has any bleeding diathesis, or must take anticoagulants or antiplatelet agents, including nonsteroidal anti inflammatory drugs, that cannot be stopped for biopsy or surgery.
  7. Patient has severe pulmonary, cardiac, or other systemic disease, specifically:

    • New York Heart Association > Class II congestive heart failure that is not controlled on standard therapy within 6 months prior to initiation of treatment with Toca 511.
    • Uncontrolled or significant cardiovascular disease, clinically significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes), clinically significant pulmonary disease (such as ≥ Grade 2 dyspnea, according to CTCAE 4.03).
    • Any other disease, either metabolic or psychological, that as per Investigator assessment may affect the patient's compliance or place the patient at an increased risk of potential treatment complications.
  8. Patient has a history of allergy or intolerance to flucytosine.
  9. Patient has a condition that would prevent him or her from being able to swallow Toca FC tablets or absorb flucytosine.
  10. Patient is human immunodeficiency virus seropositive.
  11. Patient is breast feeding.
  12. Patient has previously participated in the Toca 5 trial (Tg 511-15-01).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT02576665
Other Study ID Numbers  ICMJE Tg 511-15-02
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Tocagen Inc.
Study Sponsor  ICMJE Tocagen Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jaime R Merchan, MD University of Miami
PRS Account Tocagen Inc.
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP