TVB 2640 for Resectable Colon Cancer Other Resectable Cancers; a Window Trial.
|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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02980029|
Recruitment Status : Recruiting
First Posted : December 2, 2016
Last Update Posted : January 10, 2018
• 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
- 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.
|Condition or disease||Intervention/treatment||Phase|
|Colon Cancer||Drug: TVB-2640 Other: Placebo||Phase 1|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||48 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||Pharmacodynamic Effects of Fatty Acid Synthase (FASN) Inhibition With TVB-2640 in Resectable Colon Cancer and Other Resectable Cancers; a Window Trial.|
|Study Start Date :||January 2017|
|Estimated Primary Completion Date :||August 2018|
|Estimated Study Completion Date :||August 2018|
TVB-2640 is a potent and reversible inhibitor of the FASN enzyme.
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.
Placebo Comparator: Placebo
- 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 ]
- 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 ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02980029
|Contact: Mark B Evers, MDfirstname.lastname@example.org|
|United States, Kentucky|
|University of Kentucky||Recruiting|
|Lexington, Kentucky, United States, 40536|
|Principal Investigator:||Mark B Evers, MD||Lucille P. Markey Cancer Center at University of Kentucky|