Combination Chemotherapy with or without Ramucirumab in Treating Patients with Metastatic or Recurrent Pancreatic Cancer

Status: Active

Description

This randomized phase II trial studies how well combination chemotherapy with or without ramucirumab works in treating patients with pancreatic cancer that has spread from the primary site to other places in the body or come back after a period of time during which the cancer could not be detected. Drugs used in chemotherapy, such as fluorouracil, irinotecan hydrochloride, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as ramucirumab, may interfere with the ability of tumor cells to grow and spread. It is not yet known if combination chemotherapy is more effective with or without ramucirumab in treating patients with pancreatic cancer.

Eligibility Criteria

Inclusion Criteria

  • Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information; Note: HIPAA authorization may be included in the informed consent or obtained separately
  • 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 < 1 g protein 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)
  • Hemoglobin >= 9 g/dL
  • Absolute neutrophil count (ANC) >= 1,500/mm^3
  • Platelet count (PLT) >= 100,000/mm^3
  • Creatinine =< 1.5 mg/dL or creatinine clearance >= 40 mL/min * If serum creatinine is > 1.5 times the upper limit of normal (ULN), a 24-hour urine collection to calculate creatinine clearance must be performed
  • Albumin >= 2.5 g/dL
  • Bilirubin =< 1.5 mg/dL
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x ULN or < 5 x ULN in the setting of liver metastases
  • The subject has adequate coagulation function as defined by international normalized ratio (INR) =< 1.5 and a partial thromboplastin time (PTT) (PTT/aPTT) < 1.5 x ULN * Patients receiving warfarin must be switched to low molecular weight heparin and have achieved stable coagulation profile prior to first dose of protocol therapy

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 (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
  • Gastrointestinal (GI) perforation/fistula
  • Documented and/or symptomatic or known brain or leptomeningeal metastases
  • Severely immune-compromised (other than being on steroids) including known human immunodeficiency virus (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; serum pregnancy test for women of child-bearing potential must be performed within 7 days prior to first dose of study treatment
  • Prior autologous or allogeneic organ or tissue transplantation
  • Known allergy to any of the treatment components
  • The patient has undergone major surgery within 28 days prior to 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
  • Have 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 (nonsteroidal antiinflammatory drug [NSAID]s, including ibuprofen, naproxen, and others), dipyridamole or clopidogrel, or similar agents
  • The patient has a serious or non-healing wound, ulcer, or bone fracture within 28 days prior to first dose of protocol therapy

Locations & Contacts

Arizona

Scottsdale
Mayo Clinic in Arizona
Status: Active
Contact: Tanios Sam Bekaii-Saab
Email: bekaii-saab.tanios@mayo.edu

Georgia

Atlanta
Emory Saint Joseph's Hospital
Status: Active
Contact: Walid L. Shaib
Phone: 404-778-1900
Email: walid.shaib@emory.edu
Emory University Hospital / Winship Cancer Institute
Status: Active
Contact: Walid L. Shaib
Phone: 404-778-1900
Email: walid.shaib@emory.edu
Emory University Hospital Midtown
Status: Active
Contact: Walid L. Shaib
Phone: 404-778-1900
Email: walid.shaib@emory.edu
Johns Creek
Emory Johns Creek Hospital
Status: Approved
Contact: Walid L. Shaib
Phone: 404-778-1900
Email: walid.shaib@emory.edu

Indiana

Indianapolis
Indiana University / Melvin and Bren Simon Cancer Center
Status: Active
Contact: Bert Howard O'Neil
Email: bhoneil@iu.edu
Munster
The Community Hospital
Status: Active
Contact: Erwin L. Robin
Email: erobin@comhs.org

Kentucky

Louisville
The James Graham Brown Cancer Center at University of Louisville
Status: Active
Contact: Rebecca A. Redman
Email: raredm01@louisville.edu

Nebraska

Omaha
Nebraska Methodist Hospital
Status: Active
Contact: Timothy Huyck
Email: research@alegent.org

Pennsylvania

Gettysburg
Gettysburg Cancer Cener
Status: Active
Contact: Tina Khair
Email: drkhair@gettysburgoncology.com
Philadelphia
Thomas Jefferson University Hospital
Status: Active
Contact: Steven Jonathan Cohen
Email: steven.cohen@jefferson.edu
Willow Grove
Abington Memorial Hospital-Asplundh Cancer Pavilion
Status: Active
Contact: Steven Jonathan Cohen
Email: Steven.Cohen@jefferson.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. Estimate and compare progression free survival (PFS) of modified leucovorin calcium, fluorouracil, irinotecan hydrochloride, and oxaliplatin (mFOLFIRINOX) plus ramucirumab (RAM) versus mFOLFIRINOX plus placebo in subjects with recurrent or metastatic pancreas cancer (PCA) who present for first line chemotherapy treatment.

SECONDARY OBJECTIVES:

I. Estimate and compare the median overall survival (mOS) in each arm.

II. Evaluate and compare the response rate (RR) in each arm.

III. Evaluate and compare the toxicities in each arm.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive ramucirumab intravenously (IV) over 60 minutes, oxaliplatin IV over 2-4 hours, irinotecan hydrochloride IV over 90 minutes, and fluorouracil IV continuously over 46 hours on days 1 and 15.

ARM B: Patients receive placebo IV over 60 minutes, and oxaliplatin, irinotecan hydrochloride, and fluorouracil as in Arm A minutes on days 1 and 15.

In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 8 weeks.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Emory University Hospital / Winship Cancer Institute

Principal Investigator
Walid L. Shaib

Trial IDs

Primary ID HCRNGI14-198
Secondary IDs NCI-2016-00206, Winship3142-16, IRB00086601
Clinicaltrials.gov ID NCT02581215