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

NCT03699319 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: CASE2218
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Pancreatic Cancer

Keywords

FOLFIRINOX; CPI-613

Outcome Measures

Primary Outcomes (2)

• 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

  Two years after completion of treatment

• 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

  Up to 4 weeks from start of treatment

Secondary Outcomes (6)

• Median Progression free survival (PFS)

  Two years after completion of treatment

• Median Time to progression (TTP)

  Two years after completion of treatment

• Response rates per RECIST version 1.1

  Two years after completion of treatment

• Complete pathologic response rates (CRp)

  Two years after completion of treatment

• Resection margins

  Two years after completion of treatment

Study Arms (1)

Standard Dose Cohort: CPI-613 + mFOLFIRINOX

EXPERIMENTAL

Novel 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.

Drug: CPI 613; Drug: Oxaliplatin; Drug: Irinotecan; Drug: 5-flurouracil; Drug: Folinic acid

Interventions

CPI 613 DRUG

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

Also known as: 6, 8-bis-benzylsulfanyloctanoic acid

Standard Dose Cohort: CPI-613 + mFOLFIRINOX

Oxaliplatin DRUG

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)

Also known as: Eloxatin

Standard Dose Cohort: CPI-613 + mFOLFIRINOX

Irinotecan DRUG

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)

Also known as: Camptosar

Standard Dose Cohort: CPI-613 + mFOLFIRINOX

5-flurouracil DRUG

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)

Also known as: 5FU

Standard Dose Cohort: CPI-613 + mFOLFIRINOX

Folinic acid DRUG

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)

Also known as: Leucovorin, Calcium folinate, FA

Standard Dose Cohort: CPI-613 + mFOLFIRINOX

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• David Bajor, MD: lead

Study Sites (1)

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

devimistat; Oxaliplatin; Irinotecan; Fluorouracil; Leucovorin

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Camptothecin; Alkaloids; Heterocyclic Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Study Officials

• David Bajor, MD

  University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

  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 INVESTIGATOR
• PI Title: MD

Model Details: Single-armed study of patients with locally advanced pancreatic cancer, evaluating combination CPI-613 with modified FOLFIRINOX

Study Record Dates

• First Submitted: October 4, 2018
• First Posted: October 9, 2018
• Study Start: December 7, 2018
• Primary Completion: September 23, 2024
• Study Completion: September 23, 2024
• Last Updated: January 23, 2025

Record last verified: 2024-11

Locations

US (1)