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Pharmacodynamic Effects of Fatty Acid Synthase (FASN) Inhibition With TVB-2640 in Resectable Colon Cancer

This study is currently recruiting participants.
Verified January 2017 by Mark Evers, University of Kentucky
Sponsor:
ClinicalTrials.gov Identifier:
NCT02980029
First Posted: December 2, 2016
Last Update Posted: January 10, 2017
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.
Information provided by (Responsible Party):
Mark Evers, University of Kentucky
  Purpose
The purpose of this study is to determine if the study drug, TVB-2640, is able to affect levels of certain enzymes in subject's blood and cause changes in tumor. This study is only for people who require surgery for their colon cancer.

Condition Intervention Phase
Colon Cancer Drug: TVB-2640 Other: Placebo Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Pharmacodynamic Effects of Fatty Acid Synthase (FASN) Inhibition With TVB-2640 in Resectable Colon Cancer

Further study details as provided by Mark Evers, University of Kentucky:

Primary Outcome Measures:
  • Malonyl carnitine and tripalmitin levels will be measured in the pre- and post-treatment blood samples using mass spectrometry. [ Time Frame: Up to 56 Days ]

Secondary Outcome Measures:
  • 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 (mg/kg), TIP47(mg/kg) levels in the pre-treatment and post-treatment tumor samples will be evaluated using IHC. [ Time Frame: Up to 56 Days ]
  • Mutation status of tumors will be evaluated on DNA samples prepared from the post-treatment tumor specimens using the Clearseq comprehensive cancer panel (Agilent Technologies Inc. USA). [ Time Frame: Up to 56 Days ]
  • Levels of TVB-2640 will be measured in the post-treatment blood samples, using mass spectrometry analysis effects in patients with increased expression. [ Time Frame: Up to 56 Days ]

Estimated Enrollment: 48
Study Start Date: January 2017
Estimated Study Completion Date: August 2018
Estimated Primary Completion Date: August 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TVB-2640
TVB-2640 is a potent and reversible inhibitor of the FASN enzyme.
Drug: TVB-2640
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
Placebo
Other: Placebo
Placebo

Detailed Description:
The Purpose of study to evaluate the pharmacodynamic effects on metabolic endpoints (malonyl carnitine and tripalmitin levels) following short-term treatment with TVB-2640 in patients with resectable colon cancer.48 evaluable patients will be enrolled in the study. The accrual rate is estimated to be 4 per month.
  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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:

    1. Hemoglobin ≥ 9 g/dL
    2. ANC count ≥ 1.5 X 109/L
    3. 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.

Exclusion Criteria:

  • 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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02980029


Contacts
Contact: Mark B Evers, MD 859-257-4500 mark.evers@uky.edu

Locations
United States, Kentucky
University of Kentucky Recruiting
Lexington, Kentucky, United States, 40536
Sponsors and Collaborators
Mark Evers
Investigators
Principal Investigator: Mark B Evers, MD Lucille P. Markey Cancer Center at University of Kentucky
  More Information

Responsible Party: Mark Evers, Principal Investigator, University of Kentucky
ClinicalTrials.gov Identifier: NCT02980029     History of Changes
Other Study ID Numbers: MCC-16-GI-98
First Submitted: October 12, 2016
First Posted: December 2, 2016
Last Update Posted: January 10, 2017
Last Verified: January 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Colonic Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases