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
Overview
- Phase
- Phase 2
- Intervention
- mFOLFIRINOX
- Conditions
- Pancreatic Cancer
- Sponsor
- Walid Shaib, MD
- Enrollment
- 84
- Locations
- 8
- Primary Endpoint
- Progression Free Survival (PFS) at 9 Month
- Status
- Completed
- Last Updated
- last year
Overview
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
Investigators
Walid Shaib, MD
Sponsor-Investigator
Hoosier Cancer Research Network
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.
Arms & Interventions
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.
Intervention: mFOLFIRINOX
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.
Intervention: Ramucirumab
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
Intervention: mFOLFIRINOX
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
Intervention: Placebo
Outcomes
Primary Outcomes
Progression Free Survival (PFS) at 9 Month
Time Frame: 9 months
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. PFS is defined as time of registration until disease progression met by RECIST 1.1 or death from any cause.
Secondary Outcomes
- Overall Survival (OS)(Up to a maximum of 53 months)
- Response Rate (RR)(Up to 44 months)
- Number of Participants With Adverse Events(From date of first dose until 30 days after the last treatment, assessed up to 44 months)