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Pancreatic CancerPhase 1/2NCT03699319

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

A Phase 1/2 study testing CPI 613, Oxaliplatin and Irinotecan in people with Pancreatic Cancer, run by David Bajor, MD at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Pancreatic Cancer
What is being tested?
CPI 613, Oxaliplatin and Irinotecan
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
49 participants
Where
1 siteUnited States
Study dates
7 Dec 2018to 23 Sep 2024
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

    Cleveland, Ohio, 44106

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
CPI 613, Oxaliplatin, Irinotecan, 5-flurouracil, Folinic acid
Keywords
FOLFIRINOX, CPI-613
Medical subject headings
Pancreatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CPI 613Drug

    Also called 6, 8-bis-benzylsulfanyloctanoic acid

    Standard Dose Cohort: CPI-613, 500 mg/m2, IV infusion at a rate of 4 mL/min via a central venous port on days 1 and 3 of each cycle, every 2 weeks.

    Dose Escalation Cohort: CPI-613, 750-1000 mg/m2 IV infusion at a rate of 3 mL/min via a central venous port on days 1 and 3 of each cycle, every 2 weeks.

    Intended treatment protocol is 12 cycles (2 weeks each) or 6 months

  • OxaliplatinDrug

    Also called Eloxatin

    Administered at 65 mg/m2 given as a 2-hr IV

    Part of SOC mFOLFRINOX treatment combination of Oxaliplatin, Irniotecan, 5-flurouracil, and vitamin derivative (Folinic acid)

  • IrinotecanDrug

    Also called Camptosar

    Administered at 140 mg/m2 given as a 90-min IV infusion) via a Y-connector

    Part of SOC mFOLFRINOX treatment combination of Oxaliplatin, Irniotecan, 5-flurouracil, and vitamin derivative (Folinic acid)

  • 5-flurouracilDrug

    Also called 5FU

    Administered at 400 mg/m2 as bolus followed by a 46-hr infusion at 2400 mg/m2, starting immediately after completion of folinic acid and irinotecan

    Part of SOC mFOLFRINOX treatment combination of Oxaliplatin, Irniotecan, 5-flurouracil, and vitamin derivative (Folinic acid)

  • Folinic acidDrug

    Also called Leucovorin, Calcium folinate, FA

    Administered at 400 mg/m2 given as a 90-min infusion immediately after oxaliplatin

    Part of SOC mFOLFRINOX treatment combination of Oxaliplatin, Irniotecan, 5-flurouracil, and vitamin derivative (Folinic acid)

Study groups in NCT03699319
Study groupRoleWhat they receive
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.
Receives: Drug: CPI 613; Drug: Oxaliplatin; Drug: Irinotecan; Drug: 5-flurouracil; Drug: Folinic acid

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Survival

    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

    Measured: Two years after completion of treatment

  2. MTD of CPI-613 when given in combination with mFOLFIRINOX

    MTD of CPI-613 when given in combination with mFOLFIRINOX in the added small cohort of participants with higher doses of CPI-613 developed to redefine MTD

    Measured: Up to 4 weeks from start of treatment

Secondary outcomes (6)

  1. Median Progression free survival (PFS)

    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

    Measured: Two years after completion of treatment

  2. Median Time to progression (TTP)

    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.

    Measured: Two years after completion of treatment

  3. Response rates per RECIST version 1.1

    RECIST version 1.1 response rates including complete response, partial response and stable disease (CR+PR+SD).

    Measured: Two years after completion of treatment

  4. Complete pathologic response rates (CRp)

    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".

    Measured: Two years after completion of treatment

  5. Resection margins

    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

    Measured: Two years after completion of treatment

  6. Surgical resection rates

    Percent of participants previously determined to be borderline- or non-resectable that undergo complete surgical resection after treatment on protocol.

    Measured: Up to 4 weeks from end of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Oct 2018
  2. Study start7 Dec 2018
  3. Primary completion23 Sep 2024
  4. Study completion23 Sep 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Single-armed study of patients with locally advanced pancreatic cancer, evaluating combination CPI-613 with modified FOLFIRINOX
Masking
None (open label)
Enrolment
49 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03699319
Sponsor's protocol ID
CASE2218
Status last verified
Nov 2024
First submitted
4 Oct 2018
Last updated
23 Jan 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing CPI 613, Oxaliplatin and Irinotecan in people with Pancreatic Cancer, run by David Bajor, MD at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival (time frame: Two years after completion of treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03699319.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2025.

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