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

This study is currently recruiting participants.
Verified August 2017 by Walid Shaib, MD, Hoosier Cancer Research Network
Sponsor:
ClinicalTrials.gov Identifier:
NCT02581215
First Posted: October 20, 2015
Last Update Posted: August 21, 2017
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.
Collaborators:
Eli Lilly and Company
Hoosier Cancer Research Network
Information provided by (Responsible Party):
Walid Shaib, MD, Hoosier Cancer Research Network
  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.

Condition Intervention Phase
Pancreatic Cancer Drug: mFOLFIRINOX Drug: Ramucirumab Other: Placebo Phase 2

Study Type: Interventional
Study Design: 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
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

Resource links provided by NLM:


Further study details as provided by Walid Shaib, MD, Hoosier Cancer Research Network:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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)


Estimated Enrollment: 95
Actual Study Start Date: August 2016
Estimated Study Completion Date: October 2019
Estimated Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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
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
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.
Other: Placebo
Placebo infusion with volume calculated as if it were ramucirumab every 2 weeks.

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
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02581215


Contacts
Contact: Walid Shaib, MD 404.686.4411 walid.shaib@emory.edu
Contact: Donna Sullivan 317.634.5842 ext 40 dsullivan@hoosiercancer.org

Locations
United States, Arizona
Mayo Clinic-Arizona Recruiting
Scottsdale, Arizona, United States, 85259
Contact: JoAnn Schmidt    480-342-6057    schmidt.joann@mayo.edu   
Principal Investigator: Tanios Bekaii-Saab, MD         
United States, Georgia
Emory University: Winship Cancer Institute Recruiting
Atlanta, Georgia, United States, 30322
Contact: Walid Shaib, M.D.         
United States, Indiana
Indiana University Melvin and Bren Simon Cancer Center Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Ahmad Al-Hader       aalhader@iu.edu   
Principal Investigator: Bert O'Neil, MD         
Community Healthcare System Recruiting
Munster, Indiana, United States, 46321
Contact: Mary Shields    219-836-6879    mshields@comhs.org   
Principal Investigator: Erwin Robin, MD         
United States, Kentucky
University of Louisville, James Graham Brown Cancer Center Recruiting
Louisville, Kentucky, United States, 40202
Contact: Erika Hargis    502-217-5244    Eaharg01@louisville.edu   
Principal Investigator: Rebecca Redman, MD         
United States, Nebraska
Nebraska Methodist Hospital Recruiting
Omaha, Nebraska, United States, 68114
Contact: Marlene Watson    402-354-5831    Marlene.Watson@nmhs.org   
Principal Investigator: Timothy Huyck, MD         
United States, Pennsylvania
Gettysburg Cancer Center Recruiting
Gettysburg, Pennsylvania, United States, 17325
Contact: Vanessa Hardman    717-334-4033    vhardman@gettysburgoncology.com   
Principal Investigator: Tina Khair         
Thomas Jefferson University Kimmel Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Jessica DePue    215-964-0260    jessica.depue@jefferson.edu   
Principal Investigator: Ashwin Sama, MD, MS         
Sponsors and Collaborators
Walid Shaib, MD
Eli Lilly and Company
Hoosier Cancer Research Network
Investigators
Study Chair: Walid Shaib, MD Hoosier Cancer Research Network
  More Information

Additional Information:
Responsible Party: Walid Shaib, MD, Sponsor-Investigator, Hoosier Cancer Research Network
ClinicalTrials.gov Identifier: NCT02581215     History of Changes
Other Study ID Numbers: HCRN GI14-198
First Submitted: October 19, 2015
First Posted: October 20, 2015
Last Update Posted: August 21, 2017
Last Verified: August 2017

Keywords provided by Walid Shaib, MD, Hoosier Cancer Research Network:
mFOLFIRINOX
Ramucirumab

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Oxaliplatin
Irinotecan
Ramucirumab
Antibodies, Monoclonal
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs