NCT01835041

Brief Summary

This phase I trial studies the side effects and best dose of CPI-613 when given together with combination chemotherapy in treating patients with metastatic pancreatic cancer. Drugs used in chemotherapy, CPI-613, leucovorin calcium, fluorouracil, irinotecan hydrochloride, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
21

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Apr 2013

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

Study Start

First participant enrolled

April 1, 2013

Completed
15 days until next milestone

First Submitted

Initial submission to the registry

April 16, 2013

Completed
2 days until next milestone

First Posted

Study publicly available on registry

April 18, 2013

Completed
3.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 28, 2017

Completed
6 years until next milestone

Study Completion

Last participant's last visit for all outcomes

March 16, 2023

Completed
Last Updated

July 12, 2023

Status Verified

July 1, 2023

Enrollment Period

3.9 years

First QC Date

April 16, 2013

Last Update Submit

July 10, 2023

Conditions

Acinar Cell Adenocarcinoma of the PancreasDuct Cell Adenocarcinoma of the PancreasRecurrent Pancreatic CancerStage IV Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

  • Maximum Tolerated Dose

    of 6,8-bis(benzylthio)octanoic acid when used in combination with mFOLFIRINOX determined by dose-limiting toxicities graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0

    2 weeks

Other Outcomes (4)

  • Number of Toxicities

    Approximately 2 month after start of treatment or completion of Cycle 2

  • Overall Survival

    Approximately 6 months after start of treatment

  • Progression-Free Survival

    Approximately 2 months after start of treatment

  • +1 more other outcomes

Study Arms (1)

Treatment (6,8-bis[benzylthio]octanoic acid, mFOLFIRINOX)

EXPERIMENTAL

Patients receive 6,8-bis(benzylthio)octanoic acid IV over 2 hours on days 1 and 3. Patients also receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, and fluorouracil IV continuously over 46 hours on day 1. Treatment repeats every 2 weeks for 6 months in the absence of disease progression or unacceptable toxicity.

Drug: 6,8-bis(benzylthio)octanoic acidDrug: oxaliplatinDrug: leucovorin calciumDrug: irinotecan hydrochlorideDrug: fluorouracilOther: 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, mFOLFIRINOX)
oxaliplatinDRUG

Given IV

Also known as: 1-OHP, Dacotin, Dacplat, Eloxatin, L-OHP
Treatment (6,8-bis[benzylthio]octanoic acid, mFOLFIRINOX)
leucovorin calciumDRUG

Given IV

Also known as: CF, CFR, LV
Treatment (6,8-bis[benzylthio]octanoic acid, mFOLFIRINOX)
irinotecan hydrochlorideDRUG

Given IV

Also known as: Campto, Camptosar, CPT-11, irinotecan, U-101440E
Treatment (6,8-bis[benzylthio]octanoic acid, mFOLFIRINOX)
fluorouracilDRUG

Given IV

Also known as: 5-fluorouracil, 5-Fluracil, 5-FU
Treatment (6,8-bis[benzylthio]octanoic acid, mFOLFIRINOX)
laboratory biomarker analysisOTHER

Correlative studies

Treatment (6,8-bis[benzylthio]octanoic acid, mFOLFIRINOX)

Eligibility Criteria

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

You may qualify if:

  • Histologically and cytologically confirmed metastatic pancreatic adenocarcinoma
  • Eastern Cooperative Oncology Group (ECOG) performance status being 0-1
  • Expected survival \> 2 months
  • 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 or hormonal therapy
  • 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 oxalic 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 =\< 2.0 mg/dL or 177 µmol/L
  • International normalized ratio or INR must be =\< 1.5 unless on therapeutic blood thinners
  • +2 more criteria

You may not qualify if:

  • Endocrine or acinar pancreatic carcinoma
  • Previous radiotherapy for cerebral metastases, central nervous system (CNS) or epidural tumor
  • Prior treatment with any chemotherapy for metastatic disease from pancreatic cancer
  • Patients receiving any other standard or investigational treatment for their cancer, or any other investigational agent for any indication within the past 4 weeks prior to initiation of CPI-613 treatment
  • 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)
  • Pregnant women, or women of child-bearing potential not using reliable means of contraception (because the teratogenic potential of CPI-613 is unknown)
  • Lactating females
  • Fertile men unwilling to practice contraceptive methods during the study period
  • Life expectancy less than 2 months
  • Any condition or abnormality which may, in the opinion of the investigator, compromise the safety of patients
  • Unwilling or unable to follow protocol requirements
  • Active 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
  • Evidence of active infection, or serious infection within the past month
  • +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

Related Publications (2)

  • Liu N, Yan M, Tao Q, Wu J, Chen J, Chen X, Peng C. Inhibition of TCA cycle improves the anti-PD-1 immunotherapy efficacy in melanoma cells via ATF3-mediated PD-L1 expression and glycolysis. J Immunother Cancer. 2023 Sep;11(9):e007146. doi: 10.1136/jitc-2023-007146.

    PMID: 37678921DERIVED

  • Alistar A, Morris BB, Desnoyer R, Klepin HD, Hosseinzadeh K, Clark C, Cameron A, Leyendecker J, D'Agostino R Jr, Topaloglu U, Boteju LW, Boteju AR, Shorr R, Zachar Z, Bingham PM, Ahmed T, Crane S, Shah R, Migliano JJ, Pardee TS, Miller L, Hawkins G, Jin G, Zhang W, Pasche B. Safety and tolerability of the first-in-class agent CPI-613 in combination with modified FOLFIRINOX in patients with metastatic pancreatic cancer: a single-centre, open-label, dose-escalation, phase 1 trial. Lancet Oncol. 2017 Jun;18(6):770-778. doi: 10.1016/S1470-2045(17)30314-5. Epub 2017 May 8.

    PMID: 28495639DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

devimistatOxaliplatinLeucovorinIrinotecanFluorouracil

Condition Hierarchy (Ancestors)

Digestive System NeoplasmsNeoplasms by SiteNeoplasmsEndocrine Gland NeoplasmsDigestive System DiseasesPancreatic DiseasesEndocrine System Diseases

Intervention Hierarchy (Ancestors)

Coordination ComplexesOrganic ChemicalsFormyltetrahydrofolatesTetrahydrofolatesFolic AcidPterinsPteridinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsCoenzymesEnzymes and CoenzymesCamptothecinAlkaloidsUracilPyrimidinonesPyrimidinesHeterocyclic Compounds, 1-Ring

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

April 16, 2013

First Posted

April 18, 2013

Study Start

April 1, 2013

Primary Completion

February 28, 2017

Study Completion

March 16, 2023

Last Updated

July 12, 2023

Record last verified: 2023-07

Locations

US(1)