TVB 2640 for Resectable Colon Cancer Other Resectable Cancers; a Window Trial.

NCT02980029 | Terminated Phase 1 DMC FDA Drug

• 3 other identifiers: MCC-16-MULTI-22MCC-16-GI-98R01CA208343
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief 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.
• 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.

Conditions

Colon Cancer

Keywords

Resectable Tumors

Outcome Measures

Primary Outcomes (1)

• Malonyl carnitine and tripalmitin levels will be measured in the preand post-treatment blood samples using mass spectrometry blood samples using mass spectrometry.

  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

  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.

  Up to 56 Days

• TIP47 levels in pre-treatment (where available) and post-treatment tumor samples will be evaluated using IHC.

  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.

  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.

  Up to 56 Days

Study Arms (2)

TVB-2640

EXPERIMENTAL

TVB-2640 is a potent and reversible inhibitor of the FASN enzyme.

Drug: TVB-2640

Placebo

PLACEBO COMPARATOR

Placebo

Other: Placebo

Interventions

TVB-2640 DRUG

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.

TVB-2640

Placebo OTHER

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mark Evers: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

TVB-2640

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Study Officials

• Mark B Evers, MD

  Lucille P. Markey Cancer Center at University of Kentucky

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 12, 2016
• First Posted: December 2, 2016
• Study Start: October 6, 2017
• Primary Completion: October 22, 2023
• Study Completion: October 22, 2023
• Last Updated: October 22, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)