Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03504423
Recruitment Status : Recruiting
First Posted : April 20, 2018
Last Update Posted : April 21, 2020
Sponsor:
Information provided by (Responsible Party):
Rafael Pharmaceuticals Inc.

Tracking Information
First Submitted Date  ICMJE April 12, 2018
First Posted Date  ICMJE April 20, 2018
Last Update Posted Date April 21, 2020
Actual Study Start Date  ICMJE November 9, 2018
Estimated Primary Completion Date October 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 18, 2018)
  • Overall Response Rate (ORR) [ Time Frame: At least 6 months ]
    Defined as the rate of Complete Response (CR) plus Partial Response (PR)
  • Progression Free Survival (PFS) [ Time Frame: At least 10 months ]
    Defined as the duration from the date of randomization to the date of progressive defined as the duration from the date of randomization to the date of progressive disease or death from any cause.
Original Primary Outcome Measures  ICMJE
 (submitted: April 19, 2018)
  • Overall Response Rate (ORR) [ Time Frame: At least 6 months (minimum of 12 cycles) ]
    Defined as the rate of Complete Response (CR) plus Partial Response (PR)
  • Progression Free Survival (PFS) [ Time Frame: At least 6 months (minimum of 12 cycles) ]
    Defined as the duration from the date of randomization to the date of progressive defined as the duration from the date of randomization to the date of progressive disease or death from any cause.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 18, 2018)
  • Overall Survival (OS) [ Time Frame: At least 12 months ]
    Defined as the duration from the date of randomization to the date of death from any cause
  • Duration of Response (DOR) [ Time Frame: At least 10 months ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 19, 2018)
  • Overall Survival (OS) [ Time Frame: At least 6 months (minimum of 12 cycles) ]
    Defined as the duration from the date of randomization to the date of death from any cause
  • Duration of Response (DOR) [ Time Frame: At least 6 months (minimum of 12 cycles) ]
    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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study Evaluating Efficacy and Safety of FFX Versus Combination of CPI-613 With mFFX in Patients With Metastatic Adenocarcinoma of the Pancreas
Official Title  ICMJE 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
Brief Summary 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
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pancreatic Cancer Metastatic
Intervention  ICMJE
  • Drug: CPI 613, mFolfirinox
    CPI-613: 500mg/m2, IV infusion at a rate of 4mL/min via a central venous port. mFolfirinox: given immediately after CPI-613 administration
    Other Name: CPI-613,Oxaliplatin, folinic acid, irinotecan, flurouracil
  • Drug: Folfirinox
    Folfirinox
    Other Name: Oxaliplatin, folinic acid, irinotecan, flurouracil
Study Arms  ICMJE
  • Experimental: CPI-613, mFolfirinox

    CPI-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.

    Intervention: Drug: CPI 613, mFolfirinox
  • Active Comparator: Folfirinox

    Folfirinox

    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.

    Intervention: Drug: Folfirinox
Publications * Philip PA, Buyse ME, Alistar AT, Rocha Lima CM, Luther S, Pardee TS, Van Cutsem E. A Phase III open-label trial to evaluate efficacy and safety of CPI-613 plus modified FOLFIRINOX (mFFX) versus FOLFIRINOX (FFX) in patients with metastatic adenocarcinoma of the pancreas. Future Oncol. 2019 Oct;15(28):3189-3196. doi: 10.2217/fon-2019-0209. Epub 2019 Sep 12.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 19, 2018)
500
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2022
Estimated Primary Completion Date October 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically or cytologically confirmed metastatic Stage IV 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 highly effective 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 after last study dose and must have a negative serum or urine pregnancy test within 1 week prior to treatment initiation, at monthly interval (day 1 of every even numbered cycle), at the end of systemic exposure, and at 30 days after the systemic exposure
  • Males with female partners (of childbearing potential) and female partners (of child bearing potential) with male partners must agree to use double barrier contraceptive measure (a combination of male condom with either cap, diaphragm or sponge with spermicide) in addition to 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] (≤5x UNL if liver metastases present)
      • Alanine aminotransferase [ALT/SGPT] ≤3x UNL (≤5x UNL if liver metastases present)
      • Bilirubin (≤1.5x UNL); bilirubin ≤ 2.5 x ULN for subjects with Gilbert's syndrome
      • Serum albumin > 3.0 g/dL
    • Adequate renal function

      • serum creatinine clearance CLcr > 30 mL/min). (Cocroft-Gault Formula should be used for CrCl calculation)
    • 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 if <6 months prior to disease recurrence
  • Patients with hypersensitivity to devimistat, FFX treatment or any of their excipients
  • 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 devimistat 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)
  • Female patients who are pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 6 months after the last dose of study treatment
  • Female patients of childbearing potential with a positive pregnancy test assessed by a serum pregnancy test at screening
  • Female patients of childbearing potential unwilling to use 1 highly effective method of contraception during treatment and for 6 months after the last dose of study treatment
  • Male patients with a pregnant partner who are unwilling to practice abstinence or use a condom during treatment and for 6 months after completion of study treatment
  • Male patients unwilling to abstain from donating sperm during treatment and for 6 months after completion of study treatment
  • 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 devimistat treatment (steroids given for supportive care or in response to allergic reactions are allowed at any time)
  • Requirement for immediate palliative surgery, radiation or chemotherapy of any kind. Stenting for bile duct obstruction and need for pain medications are allowed provided all other inclusion criteria are met
  • 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
  • Contraindications to any of the FFX treatment as follows:

    • Folinic Acid

      • Calcium Folinate is contraindicated in patients who have previously shown hypersensitivity to folinate or any of the excipients.
      • Calcium Folinate Injection is contraindicated in the treatment of pernicious anemia or other megaloblastic anemias where vitamin B12 is deficient. Its use can lead to an apparent response of the hematopoietic system, but neurological damage may occur or progress if already present.
      • Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take calcium folinate tablets.
    • 5FU/ Fluorouracil

      • Fluorouracil is contraindicated in patients who have any known hypersensitivity to fluorouracil, are seriously debilitated or are suffering from bone marrow depression after radiotherapy or treatment with other antineoplastic agents, or who are suffering from a potentially serious infection.
      • Fluorouracil is strictly contraindicated in pregnant or breast-feeding women.
      • Flourouracil should not be used in the management of non-malignant disease.
      • Fluorouracil must not be taken or used concomitantly with brivudin, sorivudine and analogues. Brivudin, sorivudine and analogues are potent inhibitors of the enzyme dihydropyrimidine dehydrogenase (DPD) which degrades fluorouracil
      • In patients with known complete absence of dihydropyrimidine dehydrogenase (DPD) activity
    • Oxaliplatin

      • Oxaliplatin is contraindicated in patients who have a known history of hypersensitivity to oxaliplatin or to any of the excipients
      • are breast-feeding.
      • have myelosuppression prior to starting first course, as evidenced by baseline neutrophils <2x109/l and/or platelet count of <100x109l.
      • have a peripheral sensitive neuropathy with functional impairment prior to first course.
      • have a severely impaired renal function (creatinine clearance less than 30 ml /min)
    • Irinotecan

      • Chronic inflammatory bowel disease and/or bowel obstruction
      • History of severe hypersensitivity reactions to Irinotecan hydrochloride trihydrate or to any of the excipients
      • Bilirubin > 3 times the ULN
      • Severe bone marrow failure.
      • WHO performance status > 2.
      • Concomitant use with St John's wort
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Sanjeev Luther 585-978-1351 sanjeev.luther@rafaelpharma.com
Listed Location Countries  ICMJE France,   Israel,   Korea, Republic of,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03504423
Other Study ID Numbers  ICMJE PANC003
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Rafael Pharmaceuticals Inc.
Study Sponsor  ICMJE Rafael Pharmaceuticals Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Philip A Philip, MD, PhD, FRCP Karmanos Cancer Institute at Wayne State University
PRS Account Rafael Pharmaceuticals Inc.
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP