Clinical Trials /

CPI-613 in Combination With Modified FOLFIRINOX in Locally Advanced Pancreatic Cancer

NCT03699319

Description:

The purpose of this study is to treat participants with the combination of CPI-613 (the study drug) with FOLFIRINOX (the standard combination of drugs) to determine if it is safe and effective for participants with localized and unresectable pancreatic cancer. This study is specifically for participants who have a pancreatic cancer that is localized and not considered resectable or removable by a surgeon, without additional treatment.

Related Conditions:
  • Pancreatic Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: CPI-613 in Combination With Modified FOLFIRINOX in Locally Advanced Pancreatic Cancer
  • Official Title: A Phase II Open-Label Clinical Trial of CPI-613 in Combination With Modified FOLFIRINOX in Patients With Locally Advanced Pancreatic Cancer and Good Performance Status

Clinical Trial IDs

  • ORG STUDY ID: CASE2218
  • NCT ID: NCT03699319

Conditions

  • Pancreatic Cancer

Interventions

DrugSynonymsArms
CPI 6136, 8-bis-benzylsulfanyloctanoic acidCPI-613 + modified FOLFIRINOX

Purpose

The purpose of this study is to treat participants with the combination of CPI-613 (the study drug) with FOLFIRINOX (the standard combination of drugs) to determine if it is safe and effective for participants with localized and unresectable pancreatic cancer. This study is specifically for participants who have a pancreatic cancer that is localized and not considered resectable or removable by a surgeon, without additional treatment.

Detailed Description

      The objective of this study is to determine if CPI-613 increases overall survival (OS) when
      used in combination with modified FOLFIRINOX (mFOLFIRINOX), in participants with locally
      advanced pancreatic cancer and to assess the safety of CPI-613 + mFOLFIRINOX combination in
      participants with locally advanced pancreatic cancer. The study team would like to collect
      tissue specimens for future correlative studies and aim to estimate median progression free
      survival (PFS) and the percent resected when CPI-613 is used in combination with mFOLFIRINOX,
      in participants with locally advanced pancreatic cancer.

      This is a single-armed study of participants with locally advanced pancreatic cancer,
      evaluating combination CPI-613 with modified FOLFIRINOX. Participants will be accrued at
      University Hospitals Cleveland Medical Center over 24 months with data analysis, and
      concluded 12 months after last accrual. Approximately 33 subjects will be enrolled in this
      trial, and the total duration of therapy is 6 months. All participants will be followed until
      death or 3 years from the completion of the study. The study team expects to complete accrual
      in 24 months, and will analyze data 12 months after accrual completion. The study will be
      completed 12 months after accrual completion.
    

Trial Arms

NameTypeDescriptionInterventions
CPI-613 + modified FOLFIRINOXExperimentalNovel drug and mitochondrial inhibitor, CPI-613 in conjunction with standard-of-care FOLFRINOX.
  • CPI 613

Eligibility Criteria

        Inclusion Criteria:

          -  Subjects must have histologically or cytologically confirmed pancreatic
             adenocarcinoma.

          -  Subjects must have locally advanced (including unresectable or borderline resectable)
             pancreatic cancer based on CT or MRI imaging (pancreas protocol CT of the abdomen and
             pelvis if possible, MRI with contrast or CT with oral and IV contrast in the absence
             of a pancreas protocol CT scan, CT of the chest with or without contrast) as
             determined by the PI or Co-investigators. Patients with contrast allergies may be
             permitted without contrast scans if approved by the PI or Co-Investigators for safety
             reasons.

          -  Eastern Cooperative Oncology Group (ECOG) Performance status being 01 within 1 week of
             planned start of therapy.

          -  Subjects must have normal organ and marrow function as defined below < 2 weeks must
             be:

          -  Adequate hematologic (white blood cell [WBC] >= 3500 cells/mm3; platelet count >=
             100,000 cells/mm3; absolute neutrophil count [ANC] >=1500 cells/mm3; and hemoglobin
             >=8 g/dL).

          -  Adequate hepatic function (aspartate aminotransferase [AST/SGOT] 3x upper normal limit
             [UNL], alanine aminotransferase [ALT/SGPT] <=3x UNL, bilirubin <=1.5x UNL).

          -  Adequate renal function (serum creatinine <=2.0 mg/dL or 177 µmol/L).

          -  Adequate coagulation ("International Normalized Ratio" or INR must be <1.5) unless on
             therapeutic blood thinners.

          -  Expected survival >=3 months in the view of the PI or investigators.

          -  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 (i.e. surgical
             sterilization, or a condom used with a spermicide) during the study, unless
             documentation of infertility exists.

          -  No evidence of clinically significant active infection and no serious infection within
             the past month requiring hospitalization.

          -  Subjects must have the ability to understand and the willingness to sign a written
             informed consent document.

        Exclusion Criteria:

        The presence of any of the following will exclude a subject from study enrollment.

          -  Subjects under the age of 18 or older than 80 years of age.

          -  Subjects with endocrine or acinar pancreatic carcinoma.

          -  Subjects with resectable pancreatic cancer.

          -  Subjects with metastatic pancreatic cancer based on imaging.

          -  Subjects who have received prior surgical or medical treatment for pancreatic cancer.

          -  Subjects receiving any other standard or investigational treatment for their cancer
             with a primary goal of improving survival within the past 2 weeks prior to initiation
             of CPI-613 treatment.

          -  Pregnant women or breast feeding women, or women of child-bearing potential not using
             reliable means of contraception are excluded from this study because the teratogenic
             or abortifacient effects of CPI-613 is unknown. Because there is an unknown, but
             potential risk for adverse events in nursing infants secondary to treatment of the
             mother with CPI-613, breastfeeding should be discontinued if the mother is treated
             with CPI-613. These potential risks may also apply to other agents used in this study.

          -  Fertile men unwilling to practice contraceptive methods during the study period.

          -  Subjects with a life expectancy less than 3 months.

          -  Subjects with a serious medical illness that would potentially increase subjects' risk
             for toxicity

          -  Subjects with any active uncontrolled bleeding, and any patients with a bleeding
             diathesis (e.g., active peptic ulcer disease).

          -  Subjects with a history of myocardial infarction that is <3 months prior to
             registration.

          -  Subjects with uncontrolled intercurrent illness including, but not limited to ongoing
             or active infection, symptomatic congestive heart failure or coronary artery disease,
             unstable angina pectoris, cardiac arrhythmia, symptomatic myocardial infarction or
             psychiatric illness/social situations that would limit compliance with study
             requirements.

          -  Subjects who are known to be HIV-positive and on combination antiretroviral therapy
             are ineligible because of the potential for pharmacokinetic interactions with CPI-613.
      
Maximum Eligible Age:80 Years
Minimum Eligible Age:19 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Survival
Time Frame:Three years after start of study
Safety Issue:
Description:Interval between enrollment and death

Secondary Outcome Measures

Measure:Progression free survival (PFS)
Time Frame:Three years after start of study
Safety Issue:
Description:Time from study enrollment to progression or death from any cause
Measure:Time to progression (TTP)
Time Frame:Three years after start of study
Safety Issue:
Description:Time from enrollment to progression
Measure:RECIST version 1.1 response rates
Time Frame:Three years after start of study
Safety Issue:
Description:RECIST version 1.1 response rates including complete response, partial response and stable disease (CR+PR+SD)
Measure:Complete pathologic response rates (CRp)
Time Frame:Three years after start of study
Safety Issue:
Description:
Measure:Resection margins
Time Frame:Three years after start of study
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Jeffrey Hardacre

Trial Keywords

  • FOLFIRINOX
  • CPI-613

Last Updated

December 2, 2019