Clinical Trials /

Study Evaluating Efficacy and Safety of FFX Versus Combination of CPI-613 With mFFX in Patients With Metastatic Adenocarcinoma of the Pancreas

NCT03504423

Description:

A prospective, multicenter, open label, randomized phase III study to evaluate efficacy and safety of FFX versus CPI-613 + mFFX in patients with metastatic adenocarcinoma of the pancreas with age range of 18 to 75 years

Related Conditions:
  • Pancreatic Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Phase III Randomized Trial of 500 Patients With Metastatic Adenocarcinoma of the Pancreas
  • Official Title: A Phase III Multicenter Open-label Randomized Trial to Evaluate Efficacy and Safety of Folfirinox (FFX) Versus Combination of CPI-613 With Modified Folfirinox (mFFX) in Patients With Metastatic Adenocarcinoma of the Pancreas

Clinical Trial IDs

  • ORG STUDY ID: PANC003
  • NCT ID: NCT03504423

Conditions

  • Pancreatic Cancer Metastatic

Interventions

DrugSynonymsArms
CPI 613, mFolfirinoxCPI-613,Oxaliplatin, folinic acid, irinotecan, flurouracilCPI-613, mFolfirinox
FolfirinoxOxaliplatin, folinic acid, irinotecan, flurouracilFolfirinox

Purpose

A prospective, multicenter, open label, randomized phase III study to evaluate efficacy and safety of FFX versus CPI-613 + mFFX in patients with metastatic adenocarcinoma of the pancreas with age range of 18 to 75 years

Trial Arms

NameTypeDescriptionInterventions
CPI-613, mFolfirinoxExperimentalCPI-613, mFolfirinox CPI-613 at 500 mg/m2 IV infusion at a rate of 4mL/min via a central venous port on day 1 and 3 of a 14-day cycle. mFolfirinox (given immediately after CPI-613 administration): Oxaliplatin (Eloxatin) at 65 mg/m2 given as a 2 hr IV infusion, Folinic acid at 400 mg/m2 given as a 90 min (1.5hr) infusion immediately after Oxaliplatin, and concurrently with Irinotecan (irinotecan at 140mg/m2 given as a 90 min IV infusion) via a Y-connector, Flurouracil at 400 mg/m2 as bolus followed by a 46 hr infusion at 2400mg/m2 starting immediately after completion of folinic acid and Irinotecan.
  • CPI 613, mFolfirinox
FolfirinoxActive ComparatorFolfirinox Folfirinox: Oxaliplatin (Eloxatin) at 85 mg/m2 given as a 2 hr IV infusion, Folinic acid at 400 mg/m2 given as a 90 min (1.5hr) infusion immediately after Oxaliplatin, and concurrently with Irinotecan (irinotecan at 180mg/m2 given as a 90 min IV infusion) via a Y-connector, Flurouracil at 400 mg/m2 as bolus followed by a 46 hr infusion at 2400mg/m2 starting immediately after completion of folinic acid and Irinotecan.
  • Folfirinox

Eligibility Criteria

        INCLUSION CRITERIA

          -  Histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas

          -  No prior treatments for stage IV pancreatic adenocarcinoma (prior adjuvant or
             neoadjuvant treatment is allowed provided completed > 6 months prior to disease
             recurrence)

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1

          -  Male and female patients 18 - 75 years of age

          -  Measurable disease determined using guidelines of Response Evaluation Criteria In
             Solid Tumors (RECIST version 1.1)

          -  Expected survival >3 months

          -  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(s), intrauterine hormone releasing system (IUS), bilateral
             tubal occlusion or vasectomized partner) during and for 6 months of the study and must
             have a negative serum or urine pregnancy test within 1 week prior to treatment
             initiation, at the end of systemic exposure and between the cycles if the menstrual
             period is delayed by over 30 days.

          -  Adult subjects of child bearing potential must agree to use double barrier
             contraceptive measure, oral contraception or avoidance of intercourse during the study
             and for 6 months after last study dose is received.

          -  At least 2 weeks must have elapsed from any prior surgery with resolution of any
             sequela for randomization

          -  Laboratory values ≤2 weeks prior to randomization must be:

               -  Adequate hematologic values:

                    -  Platelet count ≥100,000 cells/mm3 or ≥100 bil/L; Absolute neutrophil count
                       [ANC] ≥1,500 cells/mm3 or ≥1.5 bil/L; Hemoglobin ≥9 g/dL or ≥90 g/L)

               -  Adequate hepatic function:

                    -  Aspartate aminotransferase [AST/SGOT] ≤3x upper normal limit [UNL] Alanine
                       aminotransferase [ALT/SGPT] ≤3x UNL (≤5x UNL if liver metastases present)
                       Bilirubin ≤1.5x UNL); does not apply to subjects with Gilbert's syndrome
                       Serum albumin > 3.0 g/dL

               -  Adequate renal function:

                    -  Serum creatinine clearance CLcr > 30 mL/min)

               -  Adequate coagulation function:

                    -  International Normalized Ratio or INR must be <1.5 unless on therapeutic
                       blood thinners)

          -  No evidence of active infection and no serious infection within the past 30 days.

          -  Mentally competent, ability to understand and willingness to sign the informed consent
             form

        EXCLUSION CRITERIA

          -  Endocrine or acinar pancreatic carcinoma

          -  Known cerebral metastases, central nervous system (CNS), or epidural tumor

          -  Prior treatment with any chemotherapy for metastatic adenocarcinoma of the pancreas

          -  Completion of a gemcitabine-based adjuvant chemotherapy regimen within less than 6
             months at the time of screening.

          -  Receipt of neoadjuvant or adjuvant FOLFIRINOX therapy

          -  Presence of clinically significant abdominal ascites

          -  Patients receiving any other standard or investigational treatment for their cancer,
             or any other investigational agent for any indication within the past 2 weeks prior to
             initiation of CPI-613 treatment

          -  Serious medical illness that would potentially increase patients' risk for toxicity

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

          -  NAP

          -  Lactating females

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

          -  Life expectancy less than 3 months

          -  Any condition or abnormality which may, in the opinion of the investigator, compromise
             the safety of patients

          -  Unwilling or unable to follow protocol requirements

          -  Active heart disease including but not limited to symptomatic congestive heart failure
             (NYHA class 3 or 4), symptomatic coronary artery disease, symptomatic angina pectoris,
             or symptomatic myocardial infarction

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

          -  Evidence of active infection, or serious infection within the past 30 days.

          -  Patients with known HIV infection

          -  Patients who have received cancer immunotherapy of any type within the past 2 weeks
             prior to initiation of CPI-613 treatment (steroids given for supportive care or in
             response to allergic reactions are allowed at any time)

          -  Requirement for immediate palliative treatment of any kind including surgery

          -  No prior malignancy except for the following: adequately treated basal or squamous
             cell skin cancer, in situ cervical cancer, adequately treated cancer from which the
             patient has been disease-free for at least 3 years prior to screening

          -  Unwilling or unable to avoid the concomitant use of strong CYP3A4 inducers or
             inhibitors during treatment with irinotecan

          -  A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a
             QTc interval > 480 milliseconds (ms) (CTCAE grade 1) using Fredericia's QT correction
             formula (i.e. QTcF)

          -  A history of additional risk factors for TdP (e.g., heart failure, hypokalemia, family
             history of long QT syndrome)

          -  The use of concomitant medications that prolong the QT/QTc intervals
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate (ORR)
Time Frame:At least 6 months
Safety Issue:
Description:Defined as the rate of Complete Response (CR) plus Partial Response (PR)

Secondary Outcome Measures

Measure:Overall Survival (OS)
Time Frame:At least 12 months
Safety Issue:
Description:Defined as the duration from the date of randomization to the date of death from any cause
Measure:Duration of Response (DOR)
Time Frame:At least 10 months
Safety Issue:
Description:The duration of overall response is the interval from date of initial documented response (CR or PR) to the first documented date of disease progression or death.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Rafael Pharmaceuticals Inc.

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