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 1/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/I 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 acidStandard Dose Cohort: CPI-613 + mFOLFIRINOX
OxaliplatinEloxatinStandard Dose Cohort: CPI-613 + mFOLFIRINOX
IrinotecanCamptosarStandard Dose Cohort: CPI-613 + mFOLFIRINOX
5-flurouracil5FUStandard Dose Cohort: CPI-613 + mFOLFIRINOX
Folinic acidLeucovorin, Calcium folinate, FAStandard Dose Cohort: CPI-613 + mFOLFIRINOX

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

      This is a single-arm study of participants with locally advanced pancreatic ductal
      adenocarcinoma evaluating combination CPI-613 with modified FOLFIRINOX, with the addition of
      a dose escalation cohort to assess safety. All study participants will get the same study
      intervention, which includes the best available treatment for locally advanced pancreatic
      cancer, plus an experimental therapy. The standard therapy is called mFOLFIRINOX, which is a
      combination of three chemotherapy drugs (Oxaliplatin, Irniotecan and 5-flurouracil) and one
      additional vitamin derivative (Folinic acid). The experimental drug is CPI-613, which
      inhibits energy production in cells, and early studies suggest that pancreatic cancer cells
      may be especially sensitive. Pre-treatment, diagnostic biopsy tissue will be collected when
      available, and clinical data will be evaluated to determine if the combination results in
      improved overall survival compared to historical experience. Based on new data, the study
      team will also attempt to identify a new maximum tolerated dose (MTD) of CPI-613 in a phase 1
      open-label dose-regimen finding study.

      The objectives of the Standard Dose Cohort are to determine the safety and efficacy of
      CPI-613, in combination with mFOLFIRINOX for locally advanced pancreatic cancer.

      The objectives of the Dose Escalation Cohort is to determine a new maximum-tolerated dose
      (MTD) of CPI-613 when given in combination with mFOLFIRINOX.
    

Trial Arms

NameTypeDescriptionInterventions
Standard Dose Cohort: CPI-613 + mFOLFIRINOXExperimentalNovel drug and mitochondrial inhibitor, CPI-613 in conjunction with standard-of-care FOLFRINOX. Consists of a Standard Dose Cohort and Dose escalation cohort using a standard 3 + 3 design starting at 750 mg/m^2 given at a rate of 4 ml/min ("dose level (DL) 2"). Participants receiving a dose of 1000mg/m^2 will be treated over 2 hours. In the absence of any DLT, the next DL will begin enrollment. If 1 DLT occurs, the DL will be expanded by 3 participants. If <33% of participants experience a DLT, the next DL will be opened and will proceed in similarly. Only 2 DLs are expected to be studied: 750 mg/m^2 and 1000 mg/m^2. Participants may be enrolled in this cohort after the accrual goal of the standard cohort is met but prior to the completion of treatment of all patients in the standard dose cohort Participants experiencing a DLT will be allowed to continue on the study at the standard DL of 500 mg or lower.
  • CPI 613
  • Oxaliplatin
  • Irinotecan
  • 5-flurouracil
  • Folinic acid

Eligibility Criteria

        Inclusion Criteria:

          -  Participants must have histologically or cytologically confirmed pancreatic
             adenocarcinoma.

          -  Participants 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. Participants 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.

          -  Participants 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.

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

        Exclusion Criteria:

          -  Participants with endocrine or acinar pancreatic carcinoma.

          -  Participants with resectable pancreatic cancer.

          -  Participants with metastatic pancreatic cancer based on imaging.

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

          -  Participants 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.

          -  Participants with a life expectancy less than 3 months.

          -  Participants with a serious medical illness that would potentially increase
             participants' risk for toxicity

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

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

          -  Participants 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.

          -  Participants 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:18 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 for participants for all participants. Median OS will be estimated using the Kaplan-Meier method along with a two-sided 80% confidence interval (CI). OS will be documented and reported separately per cohort

Secondary Outcome Measures

Measure:Median Progression free survival (PFS)
Time Frame:Three years after start of study
Safety Issue:
Description:Median (and 95% CI) time from study enrollment to progression or death from any cause for all participants. Distribution of PFS will be estimated using the Kaplan-Meier method. Participants alive at the end of follow-up are censored. PFS will be documented and reported separately per cohort
Measure:Median Time to progression (TTP)
Time Frame:Three years after start of study
Safety Issue:
Description:Median (and 95% CI) time from enrollment to progression Distribution of TTP will be estimated using the Kaplan-Meier method. Participants who die but have not progressed are censored.
Measure:Response rates per RECIST version 1.1
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:CRp defined as the proportion of participants that are designated having a complete response after treatment on protocol, evidenced by tissue samples taken during the subsequent resection CRp is defined by the NCI as "the lack of all signs of cancer in tissue samples removed during surgery or biopsy after treatment with radiation or chemotherapy".
Measure:Resection margins
Time Frame:Three years after start of study
Safety Issue:
Description:Resection margins are defined by the NCI as "The edge or border of the tissue removed in cancer surgery. The margin is described as negative or clean when the pathologist finds no cancer cells at the edge of the tissue, suggesting that all of the cancer has been removed. The margin is described as positive or involved when the pathologist finds cancer cells at the edge of the tissue, suggesting that all of the cancer has not been removed." The rate of negative resection margins will be estimates with 95 % confidence intervals
Measure:Surgical resection rates
Time Frame:Up to 4 weeks from end of treatment
Safety Issue:
Description:Percent of participants previously determined to be borderline- or non-resectable that undergo complete surgical resection after treatment on protocol.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Jeffrey Hardacre

Trial Keywords

  • FOLFIRINOX
  • CPI-613

Last Updated

January 8, 2021