A Study Of Toca 511, A Retroviral Replicating Vector, Combined With Toca FC In Patients With Solid Tumors Or Lymphoma (Toca 6)

Study Overview

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

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.

N/A

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)

BIOLOGICAL: Toca 511
DRUG: Toca FC

Tg 511-15-02

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2015-10-12	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2020-02-05
First Submitted that Met QC Criteria 2015-10-13	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2020-02-07
First Posted (ACTUAL) 2015-10-15	Results First Posted N/A	Last Verified 2020-02

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
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: 22	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 v 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

Participant Group/Arm

Intervention/Treatment

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: 22

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 v

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

Primary Outcome Measures	Measure Description	Time Frame
Changes from baseline in immune activity in tumor and peripheral blood		Baseline to Weeks 9-10

Secondary Outcome Measures	Measure Description	Time Frame

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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.

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).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Jaime R Merchan, MD, University of Miami

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Inoko K, Hiraoka K, Inagaki A, Takahashi M, Kushibiki T, Hontani K, Takano H, Sato S, Takeuchi S, Nakamura T, Tsuchikawa T, Shichinohe T, Gruber HE, Jolly DJ, Kasahara N, Hirano S. Therapeutic activity of retroviral replicating vector-mediated prodrug activator gene therapy for pancreatic cancer. Cancer Gene Ther. 2018 Aug;25(7-8):184-195. doi: 10.1038/s41417-018-0020-7. Epub 2018 May 8.
Yagiz K, Rodriguez-Aguirre ME, Lopez Espinoza F, Montellano TT, Mendoza D, Mitchell LA, Ibanez CE, Kasahara N, Gruber HE, Jolly DJ, Robbins JM. A Retroviral Replicating Vector Encoding Cytosine Deaminase and 5-FC Induces Immune Memory in Metastatic Colorectal Cancer Models. Mol Ther Oncolytics. 2017 Dec 5;8:14-26. doi: 10.1016/j.omto.2017.12.001. eCollection 2018 Mar 30.

Learn

Resources

PatientS

Caregivers

Clinical Trial Record