Colon CancerPhase 1NCT02980029
TVB 2640 for Resectable Colon Cancer Other Resectable Cancers; a Window Trial.
A Phase 1 study testing TVB-2640 in people with Colon Cancer, run by Mark Evers at 1 site in United States.
Trial summary
Primary Objective To evaluate the pharmacodynamic effects on metabolic endpoints (malonyl carnitine and tripalmitin levels) following short-term treatment with TVB-2640 in patients with resectable cancers Secondary Objectives To determine if short-term treatment with TVB-2640 decreases cancer cell proliferation. Read more about this study
- Who is it for?
- Ages 18 to 99 yearsHealthy volunteers can take part
- Conditions the study is for
- Colon Cancer
- What is being tested?
- TVB-2640
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Oct 2017to 22 Oct 2023
- 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 99 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Histologically or cytologically confirmed, resectable colon cancer without distant metastases, who are candidates for surgical resection of the tumor.
- Willing and able to provide written informed consent prior to initiation of any study procedures.
- Male or female who is ≥ 18 years of age on day of signing informed consent
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 (fully active, able to carry out all pre-disease activities without restriction) or 1 (unable to perform physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature).
- Adequate bone marrow function as evidenced by:
- Hemoglobin ≥ 9 g/dL
Show all 13Show fewer
- ANC count ≥ 1.5 X 109/L
- Platelets ≥ 100 X 109/L
- No significant ischemic heart disease or myocardial infarction (MI) within 6 months before the first dose of study drug and currently has adequate cardiac function, as evidenced by a left ventricular ejection fraction (LVEF) of ≥ 50% as assessed by multi-gated acquisition (MUGA) or ultrasound/echocardiography (ECHO); and corrected QT interval (QTc) < 470 msec
- Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Female patients of childbearing potential should be willing to use 2 methods of birth control, be surgically sterile, or abstain from heterosexual activity for the course of the study through 90 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
- Male patients should agree to use an adequate method of contraception starting with the first dose of study therapy through 90 days after the last dose of study therapy, or documented to be surgically sterile
- Willing to participate in the study and comply with all study requirements.
Who cannot join
- Inability to swallow oral medications or impairment of GI function or GI disease that may significantly alter drug absorption (including, but not limited to active inflammatory bowel disease, malabsorption syndrome). Concomitant therapy with antacids and anti-emetics is permissible
- History of risk factors for torsades de pointes (e.g., heart failure, hypokalemia, family history of long QT syndrome). Concomitant use of medications with a low risk of QT/QTc prolongation (including, but not limited to diphenhydramine, famotidine, ondansetron) is permissible.
- Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Having received cancer-directed therapy (chemotherapy, radiotherapy, hormonal therapy, biologic or immunotherapy, etc) or an investigational drug within 4 weeks (6 weeks for mitomycin C and nitrosoureas) or 5 half-lives of that agent (whichever is shorter) before the first dose of study drug.
- Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the prescreening or screening visit through 90 days after the last dose of trial treatment
- Inoperable on the basis of co-existent medical problems
- History of clinically significant dry eye (xerophthalmia) or other corneal abnormality or, if a contact lens wearer, does not agree to abstain from contact lens use from Day 1 through the last dose of study drug.
- Other concurrent disease (cardiovascular, renal, hepatic, etc.) or laboratory abnormality that, in the investigator's opinion would increase the risk of participating in the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pharmacodynamic Effects of Fatty Acid Synthase (FASN) Inhibition With TVB-2640 in Resectable Colon Cancer and Other Resectable Cancers; a Window Trial.
Primary Objective
- To evaluate the pharmacodynamic effects on metabolic endpoints (malonyl carnitine and tripalmitin levels) following short-term treatment with TVB-2640 in patients with resectable cancers
Read more
Secondary Objectives
- To determine if short-term treatment with TVB-2640 decreases cancer cell proliferation.
- To examine other biological endpoints and determine if TVB-2640 inhibits cell survival signaling and lipid biogenesis.
- To perform comprehensive metabolomic analysis in tumor tissues to identify metabolic alterations induced by TVB-2640 treatment.
- To correlate FASN levels in tumor with metabolic and biological endpoints to determine if FASN inhibition has more pronounced effects in patients with increased expression.
Read the detailed description
This study will test the hypothesis that inhibition of FASN activity blocks tumor lipid biosynthesis and alters the cellular metabolism in colon and other resectable cancers.
- The study is a randomized, double-blind, placebo-controlled pharmacodynamic study.
- Potentially eligible patients will be screened in the University of Kentucky Markey Cancer Center clinics. Eligible patients with histologically or cytologically confirmed resectable cancers without any distant metastases will be identified. Upon obtaining informed consent, patients will be enrolled into the study and randomized to TVB-2640 or placebo in a 2:1 fashion. Subjects and clinical investigators will be blinded to treatment group assignment.
- Baseline blood samples will be collected on Day 0 for all patients.
- All enrolled patients will receive the study drug (TVB-2640 or placebo) at a BSA-derived flat dose, orally once daily, starting Day 1. They will receive the study drug for 10-21 days (minimum of 10 days and a maximum of 21 days), i.e. from Day 1 to Day 10-21. The last dose of the study drug will be on the day before the surgical resection.
- For patients in both randomization groups, surgery will be performed anytime during the window of Day 11- Day 22. On the day of surgery, surgical resection specimen and blood samples will be collected.
- All patients will be evaluated and graded for adverse events according to the NCI Common Terminology for Adverse Events (CTCAE), version 4.03.
- Patients will be followed for 4 weeks after the last dose of the study drug to monitor for any drug-related adverse events.
- Conditions
- Colon Cancer
- Being tested
- TVB-2640, Placebo
- Keywords
- Resectable Tumors
- Medical subject headings
- Colonic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TVB-2640Drug
TVB-2640 is a potent and reversible inhibitor of the FASN enzyme. TVB-2640 inhibits the β-ketoacyl reductase (KR) enzymatic activity of the FASN enzyme. TVB-2640 is uncompetitive towards both NADPH and acetoacetyl-CoA in inhibiting KR activity.
PlaceboOther
Placebo
| Study group | Role | What they receive |
|---|---|---|
| TVB-2640 | Experimental | TVB-2640 is a potent and reversible inhibitor of the FASN enzyme. Receives: Drug: TVB-2640 |
| Placebo | Placebo comparator | Placebo Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Malonyl carnitine and tripalmitin levels will be measured in the preand post-treatment blood samples using mass spectrometry blood samples using mass spectrometry.
Measured: Up to 56 Days
Secondary outcomes (7)
Expression of markers of tumor growth and cell proliferation (Ki67, β-catenin, c-Myc, survivin, p-AKT, etc) in the pre- treatment (where available) and post-treatment tumor samples will be evaluated using IHC
Measured: Up to 56 Days
FASN levels in the pre-treatment and post-treatment tumor samples will be evaluated using IHCsamples will be evaluated using IHC.
Measured: Up to 56 Days
TIP47 levels in pre-treatment (where available) and post-treatment tumor samples will be evaluated using IHC.
Measured: Up to 56 Days
Comprehensive profile of cellular metabolites involved in various pathways (glycolysis, PPP, Krebs cycle, glutaminolysis) will be assessed in the post-treatment tumor samples using mass spectrometry analyses.
Measured: Up to 56 Days
Mutation status of tumors will be evaluated by the Clearseq comprehensive cancer panel, which targets over 145 cancerassociated genes, including APC, CTNNB1, TP53, PIK3CA, BRAF and KRAS.
Measured: Up to 56 Days
Levels of TVB-2640 will be measured in the post-treatment blood samples using mass spectrometry analysis.
Measured: Up to 56 Days
Toxicities will be graded as per NCI-CTCAE v4.03, based on recorded adverse events, physical examinations, and clinical laboratory assessments.
Measured: Up to 56 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2016 (estimated)
- Study start6 Oct 2017
- Primary completion22 Oct 2023
- Study completion22 Oct 2023
Why it stopped: Study was terminated by the PRMC for low accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colon 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mark Evers
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor-investigator, Mark Evers, University of Kentucky
- Investigators
- Mark B Evers, MD, Principal investigator, Lucille P. Markey Cancer Center at University of Kentucky
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02980029
- Sponsor's protocol ID
- MCC-16-MULTI-22
- Other IDs
- MCC-16-GI-98, R01CA208343
- Status last verified
- Jan 2024
- First submitted
- 12 Oct 2016
- Last updated
- 22 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacodynamic Effects of Fatty Acid Synthase (FASN) Inhibition With TVB-2640 in Resectable Colon Cancer and Other Resectable Cancers; a Window Trial.
- ClinicalTrials.gov ID
- NCT02980029
- Acronym / sponsor ID
- MCC-16-MULTI-22
- Conditions
- Colon Cancer
- Keywords
- Resectable Tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was terminated by the PRMC for low accrual
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Mark EversUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 6 Oct 2017 (actual)
- Primary completion
- 22 Oct 2023 (actual)
- Study completion
- 22 Oct 2023 (actual)
- First posted
- 2 Dec 2016 (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.
Primary Objective
- To evaluate the pharmacodynamic effects on metabolic endpoints (malonyl carnitine and tripalmitin levels) following short-term treatment with TVB-2640 in patients with resectable cancers
Secondary Objectives
- To determine if short-term treatment with TVB-2640 decreases cancer cell proliferation.
- To examine other biological endpoints and determine if TVB-2640 inhibits cell survival signaling and lipid biogenesis.
- To perform comprehensive metabolomic analysis in tumor tissues to identify metabolic alterations induced by TVB-2640 treatment.
- To correlate FASN levels in tumor with metabolic and biological endpoints to determine if FASN inhibition has more pronounced effects in patients with increased expression.
Detailed description
This study will test the hypothesis that inhibition of FASN activity blocks tumor lipid biosynthesis and alters the cellular metabolism in colon and other resectable cancers.
- The study is a randomized, double-blind, placebo-controlled pharmacodynamic study.
- Potentially eligible patients will be screened in the University of Kentucky Markey Cancer Center clinics. Eligible patients with histologically or cytologically confirmed resectable cancers without any distant metastases will be identified. Upon obtaining informed consent, patients will be enrolled into the study and randomized to TVB-2640 or placebo in a 2:1 fashion. Subjects and clinical investigators will be blinded to treatment group assignment.
- Baseline blood samples will be collected on Day 0 for all patients.
- All enrolled patients will receive the study drug (TVB-2640 or placebo) at a BSA-derived flat dose, orally once daily, starting Day 1. They will receive the study drug for 10-21 days (minimum of 10 days and a maximum of 21 days), i.e. from Day 1 to Day 10-21. The last dose of the study drug will be on the day before the surgical resection.
- For patients in both randomization groups, surgery will be performed anytime during the window of Day 11- Day 22. On the day of surgery, surgical resection specimen and blood samples will be collected.
- All patients will be evaluated and graded for adverse events according to the NCI Common Terminology for Adverse Events (CTCAE), version 4.03.
- Patients will be followed for 4 weeks after the last dose of the study drug to monitor for any drug-related adverse events.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TVB-2640 | Experimental | Drug: TVB-2640TVB-2640 is a potent and reversible inhibitor of the FASN enzyme. |
| Placebo | Placebo comparator | Other: PlaceboPlacebo |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Histologically or cytologically confirmed, resectable colon cancer without distant metastases, who are candidates for surgical resection of the tumor.
- Willing and able to provide written informed consent prior to initiation of any study procedures.
- Male or female who is ≥ 18 years of age on day of signing informed consent
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 (fully active, able to carry out all pre-disease activities without restriction) or 1 (unable to perform physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature).
- Adequate bone marrow function as evidenced by:
Key exclusion criteria (8 listed)
- Inability to swallow oral medications or impairment of GI function or GI disease that may significantly alter drug absorption (including, but not limited to active inflammatory bowel disease, malabsorption syndrome). Concomitant therapy with antacids and anti-emetics is permissible
- History of risk factors for torsades de pointes (e.g., heart failure, hypokalemia, family history of long QT syndrome). Concomitant use of medications with a low risk of QT/QTc prolongation (including, but not limited to diphenhydramine, famotidine, ondansetron) is permissible.
- Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Having received cancer-directed therapy (chemotherapy, radiotherapy, hormonal therapy, biologic or immunotherapy, etc) or an investigational drug within 4 weeks (6 weeks for mitomycin C and nitrosoureas) or 5 half-lives of that agent (whichever is shorter) before the first dose of study drug.
- Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the prescreening or screening visit through 90 days after the last dose of trial treatment
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 |
|---|---|---|
| TVB-2640TVB-2640 is a potent and reversible inhibitor of the FASN enzyme. TVB-2640 inhibits the β-ketoacyl reductase (KR) enzymatic activity of the FASN enzyme. TVB-2640 is uncompetitive towards both NADPH and acetoacetyl-CoA in inhibiting KR activity. | Drug | TVB-2640 |
| PlaceboPlacebo | Other | Placebo |
Primary outcome
Malonyl carnitine and tripalmitin levels will be measured in the preand post-treatment blood samples using mass spectrometry blood samples using mass spectrometry.
Time frame: Up to 56 Days
7 secondary outcomes
Expression of markers of tumor growth and cell proliferation (Ki67, β-catenin, c-Myc, survivin, p-AKT, etc) in the pre- treatment (where available) and post-treatment tumor samples will be evaluated using IHC
Time frame: Up to 56 Days
FASN levels in the pre-treatment and post-treatment tumor samples will be evaluated using IHCsamples will be evaluated using IHC.
Time frame: Up to 56 Days
TIP47 levels in pre-treatment (where available) and post-treatment tumor samples will be evaluated using IHC.
Time frame: Up to 56 Days
Comprehensive profile of cellular metabolites involved in various pathways (glycolysis, PPP, Krebs cycle, glutaminolysis) will be assessed in the post-treatment tumor samples using mass spectrometry analyses.
Time frame: Up to 56 Days
Mutation status of tumors will be evaluated by the Clearseq comprehensive cancer panel, which targets over 145 cancerassociated genes, including APC, CTNNB1, TP53, PIK3CA, BRAF and KRAS.
Time frame: Up to 56 Days
Levels of TVB-2640 will be measured in the post-treatment blood samples using mass spectrometry analysis.
Time frame: Up to 56 Days
Toxicities will be graded as per NCI-CTCAE v4.03, based on recorded adverse events, physical examinations, and clinical laboratory assessments.
Time frame: Up to 56 Days
Results and safety
The study was stopped early (reason given: Study was terminated by the PRMC for low accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2024.
- 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.
Mark B Evers, MD principal investigator
Lucille P. Markey Cancer Center at University of Kentucky
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TVB-2640 in people with Colon Cancer, run by Mark Evers at 1 site 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 13 inclusion and 8 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 22 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. Some participants in this study may receive a placebo. 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: Study was terminated by the PRMC for low accrual). 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?
Malonyl carnitine and tripalmitin levels will be measured in the preand post-treatment blood samples using mass spectrometry blood samples using mass spectrometry. (time frame: Up to 56 Days). 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 22 Oct 2024.