Clinical Trials /

Phase II Randomized Trial of mFOLFIRINOX +/- Ramucirumab in Advanced Pancreatic Cancer

NCT02581215

Description:

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.

Related Conditions:
  • Pancreatic Adenocarcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase II Randomized Trial of mFOLFIRINOX +/- Ramucirumab in Advanced Pancreatic Cancer
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: HCRN GI14-198
  • NCT ID: NCT02581215

Conditions

  • Pancreatic Cancer

Interventions

DrugSynonymsArms
mFOLFIRINOXArm A: Experimental Arm
RamucirumabCyramzaArm A: Experimental Arm

Purpose

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
    

Trial Arms

NameTypeDescriptionInterventions
Arm A: Experimental ArmExperimentalmFOLFIRINOX 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.
  • mFOLFIRINOX
  • Ramucirumab
Arm B: Placebo ArmPlacebo ComparatormFOLFIRINOX 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
  • mFOLFIRINOX

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:From time of registration to the time of documented progression or subject death (estimate 9 months)
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Median Overall Survival (mOS)
Time Frame:From time of registration to the time of documented progression or subject death, assessed up to 33 months
Safety Issue:
Description:mOS assessed using Kaplan-Meier Survival Analysis to compare outcomes of subjects on experimental arm vs control arm.
Measure:Response Rate (RR)
Time Frame:From time of registration to the time of documented progression or subject death, assessed up to 33 months
Safety Issue:
Description:RR assessed using RECIST v1.1
Measure:Characterize Adverse Events (AE)
Time Frame:From date of first dose until 30 days after the last treatment, assessed up to 33 months
Safety Issue:
Description:Toxicity assessed using Common Terminology Criteria for Adverse Events v4.0 (CTCAE v4.0)

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Walid Shaib, MD

Trial Keywords

  • mFOLFIRINOX
  • Ramucirumab

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