NCT02232152

Brief Summary

This pilot phase I trial studies the side effects and best dose of CPI-613 when given together with fluorouracil in treating patients with colorectal cancer that has spread to other parts of the body and cannot be removed by surgery. CPI-613 may kill tumor cells by turning off their mitochondria. Mitochondria are used by tumor cells to produce energy and are the building blocks needed to make more tumor cells. By shutting off these mitochondria, CPI-613 deprives the tumor cells of energy and other supplies that they need to survive and grow in the body. Drugs used in chemotherapy, such as fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving CPI-613 with fluorouracil may kill more tumor cells.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
19

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Jan 2015

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 2, 2014

Completed
3 days until next milestone

First Posted

Study publicly available on registry

September 5, 2014

Completed
4 months until next milestone

Study Start

First participant enrolled

January 6, 2015

Completed
4.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 19, 2019

Completed
3.9 years until next milestone

Study Completion

Last participant's last visit for all outcomes

January 11, 2023

Completed
Last Updated

August 7, 2023

Status Verified

July 1, 2023

Enrollment Period

4.1 years

First QC Date

September 2, 2014

Last Update Submit

August 2, 2023

Conditions

Mucinous Adenocarcinoma of the ColonMucinous Adenocarcinoma of the RectumRecurrent Colon CancerRecurrent Rectal CancerSignet Ring Adenocarcinoma of the ColonSignet Ring Adenocarcinoma of the RectumStage IIIA Colon CancerStage IIIA Rectal CancerStage IIIB Colon CancerStage IIIB Rectal CancerStage IIIC Colon CancerStage IIIC Rectal CancerStage IVA Colon CancerStage IVA Rectal CancerStage IVB Colon CancerStage IVB Rectal Cancer

Outcome Measures

Primary Outcomes (1)

  • MTD of 6,8-bis(benzylthio)octanoic acid in combination with fluorouracil based on the incidence of dose-limiting toxicities graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

    Up to 2 weeks

Secondary Outcomes (2)

  • Incidence of toxicity of 6,8-bis(benzylthio)octanoic acid and fluorouracil combination graded according to NCI CTCAE version 4.0

    Up to 3 years

  • PK parameters (maximum observed concentration, area under the curve, half-life, elimination rate constant, drug clearance, and volume of distribution) of 6,8-bis(benzylthio)octanoic acid in plasma samples

    Week 1: days 1 and 4 before infusion of 6,8-bis(benzylthio)octanoic acid and at 30 minutes, 1, 1.5, 2, 4, 6 and 8 (optional) hours after the completion of infusion

Other Outcomes (3)

  • Progression-free survival (PFS)

    Time from the first dose of 6,8-bis(benzylthio)octanoic acid to disease progression, assessed up to 3 years

  • Overall response rate (ORR) (i.e., sum of complete response [CR] and partial response [PR])

    Up to 3 years

  • Disease control rate (DCR) (i.e., sum of CR, PR, and stable disease)

    Up to 3 years

Study Arms (1)

Treatment (6,8-bis(benzylthio)octanoic acid, fluorouracil)

EXPERIMENTAL

Patients receive 6,8-bis(benzylthio)octanoic acid IV over 2 hours on days 1-4 and fluorouracil IV over 46 hours on days 2-4. Courses repeat every 2 weeks for 6 months in the absence of disease progression or unacceptable toxicity.

Drug: 6,8-bis(benzylthio)octanoic acidDrug: fluorouracilOther: pharmacological studyOther: laboratory biomarker analysis

Interventions

6,8-bis(benzylthio)octanoic acidDRUG

Given IV

Also known as: alpha-lipoic acid analogue CPI-613, CPI-613
Treatment (6,8-bis(benzylthio)octanoic acid, fluorouracil)
fluorouracilDRUG

Given IV

Also known as: 5-fluorouracil, 5-Fluracil, 5-FU
Treatment (6,8-bis(benzylthio)octanoic acid, fluorouracil)
pharmacological studyOTHER

Correlative studies

Also known as: pharmacological studies
Treatment (6,8-bis(benzylthio)octanoic acid, fluorouracil)
laboratory biomarker analysisOTHER

Correlative studies

Treatment (6,8-bis(benzylthio)octanoic acid, fluorouracil)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Histologically and cytologically confirmed metastatic colorectal adenocarcinoma (colon, rectal or colorectal cancer) that is not resectable
  • Have failed or have not tolerated FOLFOX, FOLFIRI and, if KRAS wild type, then a EGFR inhibitor-based regimen
  • Eastern Cooperative Oncology Group (ECOG) performance status being 0-2
  • Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use accepted contraceptive methods (abstinence, intrauterine device \[IUD\], oral contraceptive or double barrier device) during the study, and must have a negative serum or urine pregnancy test within 1 week prior to treatment initiation
  • Fertile men must practice effective contraceptive methods during the study, unless documentation of infertility exists
  • At least 2 weeks must have elapsed from any prior surgery
  • Granulocyte count \>= 1500/mm\^3
  • White blood cell (WBC) \>= 3500 cells/mm\^3 or \>= 3.5 bil/L
  • Platelet count \>= 100,000 cells/mm\^3 or \>= 100 bil/L
  • Absolute neutrophil count (ANC) \>= 1500 cells/mm\^3 or \>= 1.5 bil/L
  • Hemoglobin \>= 9 g/dL or \>= 90 g/L
  • Aspartate aminotransferase (AST/serum glutamic oxaloacetic transaminase \[SGOT\]) =\< 3 x upper normal limit (UNL), alanine aminotransferase (ALT/serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x UNL (=\< 5 x UNL if liver metastases present)
  • Bilirubin =\< 1.5 x UNL
  • Serum creatinine =\< 1.5 mg/dL or 13 umol/L
  • International normalized ratio or INR must be =\< 1.5 unless on therapeutic blood thinners
  • +3 more criteria

You may not qualify if:

  • Therapy with CPI-613 prior to participating in this trial
  • Known hypersensitivity to 5-FU injection, poor nutritional state, known dipyrimidine dehydrogenase deficiency, or taking sorivudine (such as Usevir, brovavir, etc.)
  • History of hypersensitivity to active or inactive excipients of any component of treatment
  • Previous radiotherapy for central nervous system metastases
  • Patients receiving any other standard or investigational treatment for their cancer, or any other investigational agent for any indication, within the past 2 weeks prior to initiation of treatment with study drugs
  • Serious medical illness that would potentially increase patients' risk for toxicity
  • Any active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease)
  • History of abdominal fistula or gastrointestinal perforation =\< 6 months prior to treatment with study drugs
  • Pregnant women, or women of child-bearing potential not using reliable means of contraception
  • Lactating females
  • Fertile men unwilling to practice contraceptive methods during the study period
  • Any condition or abnormality which may, in the opinion of the investigator, compromise the safety of patients
  • Unwilling or unable to follow protocol requirements
  • Symptomatic heart disease including but not limited to symptomatic congestive heart failure, symptomatic coronary artery disease, symptomatic angina pectoris, symptomatic myocardial infarction or symptomatic congestive heart failure
  • Patients with a history of myocardial infarction that is \< 3 months prior to registration
  • +5 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Comprehensive Cancer Center of Wake Forest University

Winston-Salem, North Carolina, 27157, United States

Location

MeSH Terms

Conditions

Colonic NeoplasmsRectal Neoplasms

Interventions

devimistatFluorouracil

Condition Hierarchy (Ancestors)

Colorectal NeoplasmsIntestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal Diseases

Intervention Hierarchy (Ancestors)

UracilPyrimidinonesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Study Officials

  • Caio Rocha Lima, MD

    Wake Forest University Health Sciences

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 2, 2014

First Posted

September 5, 2014

Study Start

January 6, 2015

Primary Completion

February 19, 2019

Study Completion

January 11, 2023

Last Updated

August 7, 2023

Record last verified: 2023-07

Locations

US(1)