Gastrointestinal CancerPhase 1NCT04195373
A Safety Study of TMV-018 in Patients With Tumors of the Gastrointestinal Tract
A Phase 1 study testing TMV-018 + 5-FC, TMV-018 + anti-PD-1 and TMV-018 + 5-FC + anti-PD-1 in people with Gastrointestinal Cancer, run by Themis Bioscience GmbH at 2 sites in Germany.
Trial summary
This study aims to determine the safety and tolerability of TMV-018 when given alone or in combination with the prodrug 5-Fluorocytosine (5-FC) or an anti-PD-1 checkpoint inhibitor in patients with gastrointestinal tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastrointestinal Cancer
- What is being tested?
- TMV-018 + 5-FC, TMV-018 + anti-PD-1 and TMV-018 + 5-FC + anti-PD-1
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 2 sitesGermany
- Study dates
- 23 Nov 2020to 23 Nov 2020
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed informed consent form must be obtained prior to any research procedures.
- At least 18 years of age on the day of signing the informed consent.
- Histologically confirmed diagnosis of advanced, metastatic tumors of the gastrointestinal tract (stage IV)
- Before enrollment (i.e., at least 4 weeks before study treatment): Prior chemotherapy, targeted therapy, radiotherapy, to treat cancer or major surgery have to be stopped at least 4 weeks prior to enrolment.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 and life expectancy ≥ 3 months as assessed during screening period.
- All female participants of childbearing potential, defined as all woman physiologically capable of becoming pregnant, must have a negative pregnancy test at screening.
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- Willingness not to become pregnant or to father a child during study participation by practicing reliable methods of contraception.
- Patient must have exhausted all current standard therapy lines in the target cancer indications
- Adequate organ function as determined by laboratory parameters.
Who cannot join
- Patients who participated in other studies of anti-tumor therapy within 2 weeks before enrolment.
- Patients with brain metastases.
- Patients with poorly controlled hypertension, or cardiovascular and cerebrovascular diseases with clinical significance.
- Patients with other serious organic diseases or mental disorders.
- Patients with active infections, which cannot be controlled with drugs or have potential impact on treatment, or patients with concurrent opportunistic infections.
- Patients exhibiting evidence of clinically significant immunosuppression such as primary or acquired immunodeficiency state
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- Pregnancy (positive pregnancy test at screening or before end of study participation) or lactation at screening or planning to become pregnant before completion of study participation.
- Males who have sex to conceive a child / who want to donate semen, during the study and up to 4 months after the last dose of TMV-018, 5-FC or pembrolizumab.
- Males and female subjects of childbearing potential who are unwilling to use double barrier methods of effective contraception
- Patients with an impaired renal function (creatinine clearance ≤ 40 mL/min).
- Patients currently or recently (< 2 months) taking fluconazole, itraconazole, clotrimazole troches, itraconazole, amphotericin or other oral anti-fungal medications.
- Patients with contraindications for treatment with flucytosine (5-FC)
- Known hypersensitivity to 5-FU, known deficiency in dihydropyrimidine dehydrogenase (DPD)
- Known hypersensitivity to pembrolizumab, its excipients, or other monoclonal antibody.
- Severe immune-related adverse reactions from treatment with pembrolizumab, defined as any grade 4 toxicity or grade 3 toxicity requiring corticosteroid treatment (> 10 mg/day prednisone or equivalent) for greater than 12 weeks.
- History or evidence of symptomatic autoimmune diseases.
- Other medical condition or laboratory abnormality that in the judgment of the Investigator may increase the risk associated with study participation or may interfere with interpretation of study results.
- History of severe systemic reaction or side-effect after a measles vaccination.
- Subjects who continue to experience > grade 1 Common Terminology Criteria for Adverse Events (CTCAE) toxicity due to cancer therapy within 4 weeks prior to enrollment will not be eligible.
- Use of anti-cancer treatments within 4 weeks of TMV-018 treatment start.
Trial locations and contacts
2 sites in 1 country.
Germany2 sites
University Hospital Bonn
Bonn
University Hospital Tübingen
Tübingen
About this study
Official title: A Phase I Open-label, Safety Study of Intra-tumoral Application of TMV-018 in Combination With 5-FC or Anti-PD-1 Therapy in Patients With Tumors of the Gastrointestinal Tract
This study aims to determine the safety and tolerability of TMV-018 when given alone or in combination with the prodrug 5-Fluorocytosine (5-FC) or an anti-PD-1 checkpoint inhibitor in patients with gastrointestinal tumors. Furthermore, the maximum tolerated dose (MTD) and recommended Phase II dose of TMV-018 shall be determined.
Read the detailed description
This is an open-label, multicenter, dose-escalation phase I trial that aims to determine the safety and tolerability of TMV-018, an oncolytic measles virus encoding the prodrug converting enzyme "super cytosine deaminase", when given alone or in combination with the prodrug 5-Fluorocytosine (5-FC) or an anti-PD-1 checkpoint inhibitor up to day 72 in patients with colorectal carcinoma (left-sided or rectal), esophageal carcinoma, or gastric cancer. Furthermore, the maximum tolerated dose (MTD) and recommended Phase II dose of TMV-018 shall be determined.
At least 15 patients will be enrolled. Patients will be randomized to different treatment groups: all patients will receive intra-tumoral TMV-018 on four visits and additionally 5-FC and/or anti-PD-1 treatment. All adverse events will be documented and analyzed for the primary safety endpoint. Blood and tumor samples will be collected up to day 72 to determine the safety, tolerability and immunogenicity of the treatment. The patients will be followed-up for another two years to determine long-term safety.
- Conditions
- Gastrointestinal Cancer
- Being tested
- TMV-018 + 5-FC, TMV-018 + anti-PD-1, TMV-018 + 5-FC + anti-PD-1
- Keywords
- Colorectal cancer, Esophageal cancer, Gastric cancer, TMV-018, anti-PD-1, 5-FC, oncolytic virus
- Medical subject headings
- Gastrointestinal Neoplasms, Colorectal Neoplasms, Esophageal Neoplasms, Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TMV-018 + 5-FCBiological
TMV-018: liquid frozen, life attenuated, oncolytic measles virus encoding the prodrug converting enzyme "super cytosine deaminase"; 1E+06 TCID50 to 1E+08 TCID50 per dose.
5-FC: 150 mg/kg/day for 2 days during each treatment.
TMV-018 + anti-PD-1Biological
TMV-018: liquid frozen, life attenuated, oncolytic measles virus encoding the prodrug converting enzyme "super cytosine deaminase"; 1E+06 TCID50 to 1E+08 TCID50 per dose.
Anti-PD-1 inhibitor dose according to its SMPC.
TMV-018 + 5-FC + anti-PD-1Biological
TMV-018: liquid frozen, life attenuated, oncolytic measles virus encoding the prodrug converting enzyme "super cytosine deaminase"; 1E+06 TCID50 to 1E+08 TCID50 per dose.
5-FC: 150 mg/kg/day for 2 days during each treatment cycle.
Anti-PD-1 Inhibitor: dose according to its SMPC.
| Study group | Role | What they receive |
|---|---|---|
| TMV-018 + 5-FC | Experimental | Patients will receive intra-tumoral TMV-018 on days 0, 14, 28 and 42, and will be additionally treated with the prodrug 5-FC. Receives: Biological: TMV-018 + 5-FC |
| TMV-018 + anti-PD-1 inhibitor | Experimental | Patients will receive intra-tumoral TMV-018 on days 0, 14, 28 and 42, and will be additionally treated with an anti-PD-1 Inhibitor. Receives: Biological: TMV-018 + anti-PD-1 |
| TMV-018 + 5-FC + anti-PD-1 inhibitor | Experimental | Patients will receive intra-tumoral TMV-018 on days 0, 14, 28 and 42, and will be additionally treated with the prodrug 5-FC and an anti-PD-1 Inhibitor. Receives: Biological: TMV-018 + 5-FC + anti-PD-1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of Adverse Events
Incidence of solicited and unsolicited adverse events from enrollment until end of study.
Measured: 4 years
Determine MTD and dose for phase II
Determine the maximum tolerated dose (MTD) and recommended Phase II dose of TMV-018
Measured: 1.5 years
Secondary outcomes (4)
Viral replication
Assess viral replication at injected tumor sites, viremia (distribution of i.t. applied TMV-018 into the blood stream), and shedding as well as possible persistence phenomena of TMV-018
Measured: 2 years
Viral distribution
Assess viremia (distribution of i.t. applied TMV-018 into the blood stream) and shedding as well as possible persistence phenomena of TMV-018
Measured: 2 years
Efficacy of therapy assessed by RECIST 1.1
Assess the therapeutic efficacy of TMV-018 with 5-FC or anti-PD-1 therapy by radiologic assessment (RECIST 1.1, time to progression).
Measured: 4 years
Efficacy of therapy assessed by changes in tumor marker level
Assess the therapeutic efficacy of TMV-018 with 5-FC or anti-PD-1 therapy by changes in tumor marker level.
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2019
- Study start23 Nov 2020
- Primary completion23 Nov 2020
- Study completion23 Nov 2020
Why it stopped: Study not started, no subjects recruited.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gastrointestinal 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Themis Bioscience GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Assign Data Management and Biostatistics GmbH, Optimapharm
- Responsible party
- Sponsor
- Investigators
- Ulrich Lauer, MD, Principal investigator, University Hospital Tuebingen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04195373
- Sponsor's protocol ID
- TMV-018-101
- Status last verified
- Nov 2020
- First submitted
- 5 Dec 2019
- Last updated
- 25 Nov 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Open-label, Safety Study of Intra-tumoral Application of TMV-018 in Combination With 5-FC or Anti-PD-1 Therapy in Patients With Tumors of the Gastrointestinal Tract
- ClinicalTrials.gov ID
- NCT04195373
- Acronym / sponsor ID
- TMV-018-101
- Conditions
- Gastrointestinal Cancer
- Keywords
- Colorectal cancer, Esophageal cancer, Gastric cancer, TMV-018, anti-PD-1, 5-FC, oncolytic virus
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study not started, no subjects recruited.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Themis Bioscience GmbHIndustry (pharma, biotech, devices)
- Collaborators
- Assign Data Management and Biostatistics GmbH, Optimapharm
- Study start
- 23 Nov 2020 (actual)
- Primary completion
- 23 Nov 2020 (actual)
- Study completion
- 23 Nov 2020 (actual)
- First posted
- 11 Dec 2019 (actual)
- 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.
This study aims to determine the safety and tolerability of TMV-018 when given alone or in combination with the prodrug 5-Fluorocytosine (5-FC) or an anti-PD-1 checkpoint inhibitor in patients with gastrointestinal tumors. Furthermore, the maximum tolerated dose (MTD) and recommended Phase II dose of TMV-018 shall be determined.
Detailed description
This is an open-label, multicenter, dose-escalation phase I trial that aims to determine the safety and tolerability of TMV-018, an oncolytic measles virus encoding the prodrug converting enzyme "super cytosine deaminase", when given alone or in combination with the prodrug 5-Fluorocytosine (5-FC) or an anti-PD-1 checkpoint inhibitor up to day 72 in patients with colorectal carcinoma (left-sided or rectal), esophageal carcinoma, or gastric cancer. Furthermore, the maximum tolerated dose (MTD) and recommended Phase II dose of TMV-018 shall be determined.
At least 15 patients will be enrolled. Patients will be randomized to different treatment groups: all patients will receive intra-tumoral TMV-018 on four visits and additionally 5-FC and/or anti-PD-1 treatment. All adverse events will be documented and analyzed for the primary safety endpoint. Blood and tumor samples will be collected up to day 72 to determine the safety, tolerability and immunogenicity of the treatment. The patients will be followed-up for another two years to determine long-term safety.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| TMV-018 + 5-FC | Experimental | Biological: TMV-018 + 5-FCPatients will receive intra-tumoral TMV-018 on days 0, 14, 28 and 42, and will be additionally treated with the prodrug 5-FC. |
| TMV-018 + anti-PD-1 inhibitor | Experimental | Biological: TMV-018 + anti-PD-1Patients will receive intra-tumoral TMV-018 on days 0, 14, 28 and 42, and will be additionally treated with an anti-PD-1 Inhibitor. |
| TMV-018 + 5-FC + anti-PD-1 inhibitor | Experimental | Biological: TMV-018 + 5-FC + anti-PD-1Patients will receive intra-tumoral TMV-018 on days 0, 14, 28 and 42, and will be additionally treated with the prodrug 5-FC and an anti-PD-1 Inhibitor. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Signed informed consent form must be obtained prior to any research procedures.
- At least 18 years of age on the day of signing the informed consent.
- Histologically confirmed diagnosis of advanced, metastatic tumors of the gastrointestinal tract (stage IV)
- Before enrollment (i.e., at least 4 weeks before study treatment): Prior chemotherapy, targeted therapy, radiotherapy, to treat cancer or major surgery have to be stopped at least 4 weeks prior to enrolment.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 and life expectancy ≥ 3 months as assessed during screening period.
Key exclusion criteria (20 listed)
- Patients who participated in other studies of anti-tumor therapy within 2 weeks before enrolment.
- Patients with brain metastases.
- Patients with poorly controlled hypertension, or cardiovascular and cerebrovascular diseases with clinical significance.
- Patients with other serious organic diseases or mental disorders.
- Patients with active infections, which cannot be controlled with drugs or have potential impact on treatment, or patients with concurrent opportunistic infections.
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 |
|---|---|---|
| TMV-018 + 5-FCTMV-018: liquid frozen, life attenuated, oncolytic measles virus encoding the prodrug converting enzyme "super cytosine deaminase"; 1E+06 TCID50 to 1E+08 TCID50 per dose. 5-FC: 150 mg/kg/day for 2 days during each treatment. | Biological | TMV-018 + 5-FC |
| TMV-018 + anti-PD-1TMV-018: liquid frozen, life attenuated, oncolytic measles virus encoding the prodrug converting enzyme "super cytosine deaminase"; 1E+06 TCID50 to 1E+08 TCID50 per dose. Anti-PD-1 inhibitor dose according to its SMPC. | Biological | TMV-018 + anti-PD-1 inhibitor |
| TMV-018 + 5-FC + anti-PD-1TMV-018: liquid frozen, life attenuated, oncolytic measles virus encoding the prodrug converting enzyme "super cytosine deaminase"; 1E+06 TCID50 to 1E+08 TCID50 per dose. 5-FC: 150 mg/kg/day for 2 days during each treatment cycle. Anti-PD-1 Inhibitor: dose according to its SMPC. | Biological | TMV-018 + 5-FC + anti-PD-1 inhibitor |
Primary outcome
Frequency of Adverse Events
Time frame: 4 years
Incidence of solicited and unsolicited adverse events from enrollment until end of study.
Determine MTD and dose for phase II
Time frame: 1.5 years
Determine the maximum tolerated dose (MTD) and recommended Phase II dose of TMV-018
4 secondary outcomes
Viral replication
Time frame: 2 years
Viral distribution
Time frame: 2 years
Efficacy of therapy assessed by RECIST 1.1
Time frame: 4 years
Efficacy of therapy assessed by changes in tumor marker level
Time frame: 4 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2020.
- Individual participant dataSharing planned: No
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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.
Ulrich Lauer, MD principal investigator
University Hospital Tuebingen
2 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 TMV-018 + 5-FC, TMV-018 + anti-PD-1 and TMV-018 + 5-FC + anti-PD-1 in people with Gastrointestinal Cancer, run by Themis Bioscience GmbH at 2 sites in Germany.
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 9 inclusion and 20 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: withdrawn, as of the sponsor's last update on 25 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany. 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 withdrawn before enrolling participants, so there are no results.
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?
Frequency of Adverse Events (time frame: 4 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 25 Nov 2020.