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Trial record 1 of 1 for:    NCT02581215
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Phase II Randomized Trial of mFOLFIRINOX +/- Ramucirumab in Advanced Pancreatic Cancer

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ClinicalTrials.gov Identifier: NCT02581215
Recruitment Status : Active, not recruiting
First Posted : October 20, 2015
Last Update Posted : November 13, 2019
Sponsor:
Collaborators:
Eli Lilly and Company
Hoosier Cancer Research Network
Information provided by (Responsible Party):
Walid Shaib, MD, Hoosier Cancer Research Network

Tracking Information
First Submitted Date  ICMJE October 19, 2015
First Posted Date  ICMJE October 20, 2015
Last Update Posted Date November 13, 2019
Actual Study Start Date  ICMJE August 2016
Estimated Primary Completion Date October 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 19, 2015)
Progression Free Survival (PFS) [ Time Frame: From time of registration to the time of documented progression or subject death (estimate 9 months) ]
PFS assessed using Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1) to compare outcomes of subjects on experimental arm vs control arm.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 19, 2015)
  • Median Overall Survival (mOS) [ Time Frame: From time of registration to the time of documented progression or subject death, assessed up to 33 months ]
    mOS assessed using Kaplan-Meier Survival Analysis to compare outcomes of subjects on experimental arm vs control arm.
  • Response Rate (RR) [ Time Frame: From time of registration to the time of documented progression or subject death, assessed up to 33 months ]
    RR assessed using RECIST v1.1
  • Characterize Adverse Events (AE) [ Time Frame: From date of first dose until 30 days after the last treatment, assessed up to 33 months ]
    Toxicity assessed using Common Terminology Criteria for Adverse Events v4.0 (CTCAE v4.0)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase II Randomized Trial of mFOLFIRINOX +/- Ramucirumab in Advanced Pancreatic Cancer
Official Title  ICMJE Phase II Randomized, Double-Blind Study of mFOLFIRINOX Plus Ramucirumab Versus mFOLFIRINOX Plus Placebo in Advanced Pancreatic Cancer Patients: Hoosier Cancer Research Network GI14-198
Brief Summary This is a phase II, multicenter, double-blinded, randomized, 2-arm trial evaluating the efficacy and safety of mFOLFIRINOX plus ramucirumab (Arm A) vs. mFOLFIRINOX plus placebo (Arm B) in 94 subjects with advanced pancreatic cancer, not amenable to curative treatment. Both arms will continue treatment until disease progression or unacceptable toxicity.
Detailed Description

OUTLINE: This is a multi-center study.

EXPERIMENTAL ARM A:

  • Oxaliplatin 85 mg/m^2 over 2-4 hours
  • Irinotecan 165 mg/m^2 over 90 minutes
  • 5-FU 2,400 mg/m^2 as a 46-hour continuous infusion without the 5-FU bolus to decrease the risk of neutropenia.
  • Arm A will receive ramucirumab (RAM) administered as an intravenous infusion over 60 minutes (infusion rate should not exceed 25 mg/min), at a fixed dose of 8 mg/kg every 2 weeks.

CONTROL ARM B :

  • Oxaliplatin 85 mg/m2 over 2-4 hours
  • Irinotecan 165 mg/m2 over 90 minutes
  • 5-FU 2,400 mg/m2 as a 46-hour continuous infusion without the 5-FU bolus to decrease the risk of neutropenia.
  • Arm B will receive a placebo infusion every 2 weeks. Due to the double-blinded nature of this study, the volume of placebo will be calculated as if it were RAM.

In order to demonstrate adequate organ function, all screening labs must be obtained within 7 days prior to registration:

Hematological:

  • Hemoglobin ≥ 9 g/dL
  • Absolute Neutrophil Count (ANC) ≥ 1,500/mm^3
  • Platelet Count (PLT) ≥ 100,000/mm^3

Renal:

  • Creatinine ≤ 1.5 mg/dL or Creatinine clearance^1 ≥ 40 mL/min
  • Albumin ≥ 2.5 g/dL

Hepatic:

  • Bilirubin ≤ 1.5 mg/dL
  • Aspartate aminotransferase (AST) ≤ 3 × ULN or < 5 xULN in the setting of liver metastases
  • Alanine aminotransferase (ALT) ≤ 3 × ULN or < 5 xULN in the setting of liver metastases

Coagulation:

  • International Normalized Ratio (INR) (Patients receiving warfarin must be switched to low molecular weight heparin and have achieved stable coagulation profile prior to first dose of protocol therapy) ≤1.5 and a partial thromboplastin time (PTT) (PTT/aPTT) < 1.5 x ULN
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Site pharmacy staff will be unblinded to the study treatment. Subjects, site investigators, site analysis teams, and other site personnel will be blinded to the study treatment.
Primary Purpose: Treatment
Condition  ICMJE Pancreatic Cancer
Intervention  ICMJE
  • Drug: mFOLFIRINOX

    mFOLFIRINOX:

    • Oxaliplatin 85 mg/m2 over 2-4 hours
    • Irinotecan 165 mg/m2 over 90 minutes
    • 5-FU 2,400 mg/m2 as a 46-hour continuous infusion without the 5-FU bolus to decrease the risk of neutropenia.
  • Drug: Ramucirumab
    Ramucirumab administered as an intravenous infusion over 60 minutes (infusion rate should not exceed 25 mg/min), at a fixed dose of 8 mg/kg every 2 weeks.
    Other Name: Cyramza
  • Other: Placebo
    Placebo infusion with volume calculated as if it were ramucirumab every 2 weeks.
Study Arms  ICMJE
  • Experimental: Arm A: Experimental Arm

    mFOLFIRINOX will be administered every 2 weeks, and consist of:

    • Oxaliplatin 85 mg/m2 over 2-4 hours
    • Irinotecan 165 mg/m2 over 90 minutes
    • 5-FU 2,400 mg/m2 as a 46-hour continuous infusion without the 5-FU bolus to decrease the risk of neutropenia.
    • Arm A will receive ramucirumab administered as an intravenous infusion over 60 minutes (infusion rate should not exceed 25 mg/min), at a fixed dose of 8 mg/kg every 2 weeks.
    Interventions:
    • Drug: mFOLFIRINOX
    • Drug: Ramucirumab
  • Placebo Comparator: Arm B: Placebo Arm

    mFOLFIRINOX will be administered every 2 weeks, and consist of:

    • Oxaliplatin 85 mg/m2 over 2-4 hours
    • Irinotecan 165 mg/m2 over 90 minutes
    • 5-FU 2,400 mg/m2 as a 46-hour continuous infusion without the 5-FU bolus to decrease the risk of neutropenia.
    • Arm B will receive a placebo infusion every 2 weeks. Due to the double-blinded nature of this study, the volume of placebo will be calculated as if it were ramucirumab
    Interventions:
    • Drug: mFOLFIRINOX
    • Other: Placebo
Publications * Not Provided

*   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 Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: October 19, 2015)
95
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2021
Estimated Primary Completion Date October 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information. .
  • Age ≥ 18 years at the time of consent.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 within 7 days prior to registration.
  • Histologic or cytological diagnosis of recurrent or metastatic pancreas adenocarcinoma (PCA) who present for first line chemotherapy treatment.
  • No prior first line systemic treatment (prior adjuvant or neoadjuvant treatment is permitted). Subjects whose disease has progressed after 6 months of last systemic chemotherapy or chemo-radiation in the adjuvant or neoadjuvant setting are eligible.
  • Measurable disease determined using guidelines of Response Evaluation Criteria In Solid Tumors (RECIST 1.1). Baseline tumor assessment should be performed using high resolution computed tomography (CT) scans or magnetic resonance imaging (MRI).
  • Urine protein < 1+ on dipstick test or routine urinalysis. If the proteinuria on these tests is ≥2+, then a 24-hour urine test must be collected and must demonstrate < 1g proteins in 24 hours to allow participation.
  • Estimated life expectancy of >12 weeks, as assessed by the site investigator.
  • If sexually active, must be postmenopausal, surgically sterile, or using effective contraception (hormonal or barrier methods) due to unknown risk of teratogenicity of ramucirumab

Exclusion Criteria:

  • Subjects with histology other than adenocarcinoma; Examples include: neuroendocrine tumors, acinar cell cancer, sarcoma or lymphoma of the pancreas.
  • Ongoing or active infection.
  • Symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia. Symptomatic heart failure per New York Heart Association (NYHA) Class II-IV.
  • Uncontrolled or poorly-controlled hypertension (>160 mmHg systolic or > 100 mmHg diastolic for >4 weeks) despite standard medical management.
  • Acute or sub-acute intestinal obstruction.
  • Interstitial pneumonia or interstitial fibrosis of the lung, which in the opinion of the site investigator could compromise the subject or the study.
  • Pleural effusion or ascites that causes > grade 1 dyspnea.
  • Cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis (any degree) with a history of hepatic encephalopathy or clinical meaningful ascites resulting from cirrhosis; clinically meaningful ascites is defined as ascites resulting from cirrhosis and requiring ongoing treatment with diuretics and/or paracentesis.
  • Grade 3 or higher bleeding event ≤ 3 months prior to randomization.
  • Experience of any arterial thrombotic or arterial thromboembolic events, including, but not limited to myocardial infarction, transient ischemic attack, or cerebrovascular accident, ≤ 6 months prior to randomization.
  • History of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered "significant") during the 3 months prior to randomization.
  • Documented and/or symptomatic or known brain or leptomeningeal metastases.
  • GI perforation/fistula
  • Documented and/or symptomatic or known brain or leptomeningeal metastases.
  • Severely immune-compromised (other than being on steroids), including known HIV infection.
  • Concurrent active malignancy other than adequately treated non-melanoma skin cancer, other noninvasive carcinoma, or in situ neoplasm. A subject with previous history of malignancy is eligible, provided that he/she has been disease free for > 3 years.
  • Breast-feeding or pregnant.
  • Prior autologous or allogeneic organ or tissue transplantation.
  • Known allergy to any of the treatment components.
  • Major surgery within 28 days prior to the first dose of protocol therapy, or minor surgery/subcutaneous venous access device placement within 2 days prior to first dose of protocol therapy. The patient has elective or planned major surgery to be performed during the course of the clinical trial.
  • Any condition that does not permit compliance with the study schedule including psychological, geographical or medical.
  • Receiving medications that can effect clotting ability: warfarin, aspirin (once-daily aspirin use- maximum dose 325 mg/day is permitted), nonsteroidal anti-inflammatory drugs (NSAIDs, including ibuprofen, naproxen, and others), dipyridamole or clopidogrel, or similar agents. .
  • Serious or non-healing wound, ulcer, or bone fracture within 28 days prior to first dose of protocol therapy.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02581215
Other Study ID Numbers  ICMJE HCRN GI14-198
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Walid Shaib, MD, Hoosier Cancer Research Network
Study Sponsor  ICMJE Walid Shaib, MD
Collaborators  ICMJE
  • Eli Lilly and Company
  • Hoosier Cancer Research Network
Investigators  ICMJE
Study Chair: Walid Shaib, MD Hoosier Cancer Research Network
PRS Account Hoosier Cancer Research Network
Verification Date November 2019

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