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.
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
Interventions
Drug | Synonyms | Arms |
---|
CPI 613 | 6, 8-bis-benzylsulfanyloctanoic acid | Standard Dose Cohort: CPI-613 + mFOLFIRINOX |
Oxaliplatin | Eloxatin | Standard Dose Cohort: CPI-613 + mFOLFIRINOX |
Irinotecan | Camptosar | Standard Dose Cohort: CPI-613 + mFOLFIRINOX |
5-flurouracil | 5FU | Standard Dose Cohort: CPI-613 + mFOLFIRINOX |
Folinic acid | Leucovorin, Calcium folinate, FA | Standard 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
Name | Type | Description | Interventions |
---|
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. | - 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
Last Updated
January 8, 2021