Colorectal CancerPhase 1NCT02576665
A Study of Toca 511, a Retroviral Replicating Vector, Combined With Toca FC in Patients With Solid Tumors or Lymphoma (Toca 6)
A Phase 1 study testing Toca 511 and Toca FC in people with Colorectal Cancer and Triple Negative Breast Cancer, run by Tocagen Inc. at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Colorectal Cancer, Triple Negative Breast Cancer, Pancreatic Cancer
- What is being tested?
- Toca 511 and Toca FC
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 3 sitesUnited States
- Study dates
- Jul 2016to 20 Dec 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient has given written informed consent.
- Patient is between 18 and 75 years of age, inclusive.
- Patient has an advanced malignancy that has progressed or recurred following standard therapy for advanced disease, and for which no curative therapies are available.
- 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.
- Patient has an estimated life expectancy of at least 6 months.
- Patient has adequate organ function, as indicated by the following laboratory values
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- 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.
- 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).
- 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.
- 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.
- Patient has a tumor amenable to injection of Toca 511 (ie, ≥ 2 cm and not close to or invading major vessels).
- Patient has an ECOG Performance Status score of 0 or 1 (solid tumors) or KPS score ≥ 70 (rHGG).
- Patient has measurable disease by RECIST version 1.1 (solid tumors) or Lugano (lymphoma) criteria or evaluable or measureable disease by Macdonald criteria (rHGG).
- 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.
Who cannot join
- 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.
- Patient has or had any active infection requiring antibiotic, antifungal, or antiviral therapy within the 2 weeks prior to administration of Toca 511.
- Patient received chemotherapy within 2 weeks prior to initiation of treatment with Toca 511 (6 weeks for nitrosoureas).
- 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.
- 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.
- 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.
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- 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.
- Patient has a history of allergy or intolerance to flucytosine.
- Patient has a condition that would prevent him or her from being able to swallow Toca FC tablets or absorb flucytosine.
- Patient is human immunodeficiency virus seropositive.
- Patient is breast feeding.
- Patient has previously participated in the Toca 5 trial (Tg 511-15-01).
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Sarah Cannon Research Institute
Denver, Colorado, 80218
MD Anderson Cancer Center
Houston, Texas, 77030
University of Miami
Miami, Florida, 33136
About this study
Official title: A Phase 1b Study of Toca 511, a Retroviral Replicating Vector, Combined With Toca FC in Patients With Solid Tumors or Lymphoma
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.
- Conditions
- Colorectal Cancer, Triple Negative Breast Cancer, Pancreatic Cancer, Non-Small Cell Lung Cancer, Head and Neck Cancer, Ovarian Cancer
- Being tested
- Toca 511, Toca FC
- Keywords
- Anaplastic Astrocytoma, Glioblastoma
- Medical subject headings
- Colorectal Neoplasms, Triple Negative Breast Neoplasms, Pancreatic Neoplasms, Carcinoma, Non-Small-Cell Lung, Head and Neck Neoplasms, Ovarian Neoplasms, Lymphoma, Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Toca 511Biological
Also called vocimagene amiretrorepvec, RRV, retroviral replicating viral
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
Toca FCDrug
Also called Flucytosine, 5-FC, 5-Fluorocytosine
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
| Study group | Role | What they receive |
|---|---|---|
| Toca 511/Toca FC | Experimental | 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. Receives: Biological: Toca 511; Drug: Toca FC |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes from baseline in immune activity in tumor and peripheral blood
Measured: Baseline to Weeks 9-10
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2015 (estimated)
- Study startJul 2016
- Primary completionMay 2019
- Study completion20 Dec 2019
Why it stopped: Sponsor decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tocagen Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jaime R Merchan, MD, Principal investigator, University of Miami
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02576665
- Sponsor's protocol ID
- Tg 511-15-02
- Status last verified
- Feb 2020
- First submitted
- 12 Oct 2015
- Last updated
- 7 Feb 2020
- Results posted
- No
- Data monitoring committee
- No
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.
PubMed 29735994Yagiz 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.
PubMed 29322091
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b Study of Toca 511, a Retroviral Replicating Vector, Combined With Toca FC in Patients With Solid Tumors or Lymphoma
- ClinicalTrials.gov ID
- NCT02576665
- Acronym / sponsor ID
- Tg 511-15-02
- Conditions
- Colorectal Cancer, Triple Negative Breast Cancer, Pancreatic Cancer, Non-Small Cell Lung Cancer, Head and Neck Cancer, Ovarian Cancer
- Keywords
- Anaplastic Astrocytoma, Glioblastoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decision
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Tocagen Inc.Industry (pharma, biotech, devices)
- Study start
- Jul 2016 (actual)
- Primary completion
- May 2019 (actual)
- Study completion
- 20 Dec 2019 (actual)
- First posted
- 15 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Toca 511/Toca FC | Experimental | Biological: Toca 511, Drug: Toca FCToca 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Patient has given written informed consent.
- Patient is between 18 and 75 years of age, inclusive.
- Patient has an advanced malignancy that has progressed or recurred following standard therapy for advanced disease, and for which no curative therapies are available.
- 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.
- Patient has an estimated life expectancy of at least 6 months.
Key exclusion criteria (15 listed)
- 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.
- Patient has or had any active infection requiring antibiotic, antifungal, or antiviral therapy within the 2 weeks prior to administration of Toca 511.
- Patient received chemotherapy within 2 weeks prior to initiation of treatment with Toca 511 (6 weeks for nitrosoureas).
- 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.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Toca 511Also: vocimagene amiretrorepvec, RRV, retroviral replicating viralToca 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 | Biological | Toca 511/Toca FC |
| Toca FCAlso: Flucytosine, 5-FC, 5-FluorocytosineToca 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 | Drug | Toca 511/Toca FC |
Primary outcome
Changes from baseline in immune activity in tumor and peripheral blood
Time frame: Baseline to Weeks 9-10
Results and safety
The study was stopped early (reason given: Sponsor decision). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2020.
- Derived from this study: PubMed 29735994Inoko 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.
- Derived from this study: PubMed 29322091Yagiz 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jaime R Merchan, MD principal investigator
University of Miami
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Toca 511 and Toca FC in people with Colorectal Cancer and Triple Negative Breast Cancer, run by Tocagen Inc. at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 7 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Sponsor decision). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes from baseline in immune activity in tumor and peripheral blood (time frame: Baseline to Weeks 9-10). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02576665, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Feb 2020.