FOLFOX Plus Regorafenib in Patients With Unresectable or Metastatic Esophagogastric Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01913639
First received: July 29, 2013
Last updated: July 21, 2014
Last verified: July 2014
  Purpose

The purpose of this study is to evaluate the effects, good and/or bad, of the drug regorafenib with chemotherapy regime (FOLFOX). This is a a Phase II trial that will study if this new treatment is effective and safe in patients with esophagus and stomach cancer.


Condition Intervention Phase
Esophageal Cancer
Gastric Cancer
Drug: Regorafenib
Drug: 5-Fluorouracil
Drug: Leucovorin
Drug: Oxaliplatin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of FOLFOX Plus Regorafenib in Patients With Unresectable or Metastatic Esophagogastric Cancer

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • progression free survival (PFS) [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • overall survival (OS) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Overall survival will be measured from the start of treatment to death or last follow-up and will be estimated using the Kaplan-Meier method

  • response rate [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    This is defined as the percentage of patients who have achieved either an objective complete or partial target lesion response that is confirmed on the RECIST 1.1 criteria. Complete or partial responses will be confirmed with repeat CT evaluation after 4 weeks.

  • Toxicity [ Time Frame: 2 weeks (14 days) prior to receiving study treatment (+/- 7 days) ] [ Designated as safety issue: Yes ]
    The type, frequency, severity, timing, and relationship of each adverse event will be determined as per the NCI Common Toxicity Criteria, version 4.0. Toxicity during cycle 1 and subsequent cycles will be reported.


Estimated Enrollment: 36
Study Start Date: July 2013
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: FOLFOX Plus Regorafenib
Regorafenib 160 mg daily on days 4 to 10 and days 18 to 24 as four 40 mg coprecipitate tablets + mFOLFOX on Day 1 and Day 15 of each cycle. Each cycle consists of 28 days. All patients will receive systemic chemotherapy with the mFOLFOX regimen and regorafenib. The specific version of the FOLFOX regimen used at MSKCC is mFOLFOX6. mFOLFOX6 will be given on Day 1 of each cycle. Patients will receive Oxaliplatin 85 mg/m2 IV (over 120 minutes), leucovorin 400 mg/m2 IV (over 120 minutes), 5-FU 400 mg/m2 IVP, and 5-FU 1200 mg/m2/day CIVI x 2 days, every two weeks. Treatment will be performed on the scheduled day ± 7 days. In case of discontinuation of FOLFOX due to cumulative toxicity and administration as a single agent during the study, regorafenib for patient convenience will be administered 160 mg daily for 3 weeks on/1 week off. The 3 weeks on/1 week off schedule is supported by the single agent regorafenib data in colon cancer and GIST.
Drug: Regorafenib
Other Name: (Bay 73-4506)
Drug: 5-Fluorouracil Drug: Leucovorin Drug: Oxaliplatin

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient must have histologically or cytologically confirmed metastatic or unresectable esophageal, gastroesophageal junction or gastric adenocarcinoma.
  • Patient must have disease that can be evaluated radiographically. This may be measurable disease or non-measurable disease. Minimum indicator lesion size = 10 mm by helical CT or = 20 mm by conventional techniques. Pathological nodes must be = 15 mm by the short axis to be considered measurable.
  • Subject must be able to swallow and retain oral medication
  • Age 18 years or older.
  • Karnofsky performance status > or = to 70%
  • Peripheral neuropathy ≤ grade 1
  • Hematologic (minimal values) White blood cell count > or = to 3000/mm3© Absolute neutrophil count > 1500 cells/ mm3 Hemoglobin > or = to 8.0 g/dl Platelet count > or = to 90,000 / mm3 Total bilirubin ≤ 1.5 x the upper limits of normal (ULN)
  • Alanine aminotransferase (ALT) and aspartate amino-transferase (AST) ≤ 2.5 x ULN (≤ 5 x ULN for subjects with liver involvement of their cancer)
  • Alkaline phosphatase limit ≤ 2.5 x ULN (≤ 5 x ULN for subjects with liver involvement of their cancer). Patients with alkaline phosphatase elevation secondary to the bony metastases rather than liver dysfunction may proceed with treatment on protocol after discussion with the principal investigator.
  • Serum creatinine ≤ 1.5 x the ULN
  • Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of study drug. Post-menopausal women (defined as no menses for at least 1 year) and surgically sterilized women are not required to undergo a pregnancy test..
  • Patients with prior deep vein thrombosis (DVT) or pulmonary embolism (PE) currently on an stable anticoagulation regimen with low molecular weight heparin (LMWH) or rivaroxaban will be permitted.

Exclusion Criteria:

  • Uncontrolled hypertension (systolic pressure >140 mm Hg or diastolic pressure > 90 mm Hg on repeated measurement) despite optimal medical management.
  • Active or clinically significant cardiac disease including:
  • Congestive heart failure - New York Heart Association (NYHA) > Class II.
  • Active coronary artery disease.
  • Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin.
  • Unstable angina (anginal symptoms at rest), new-onset angina within 3 months before randomization, or myocardial infarction within 6 months before randomization.
  • Evidence or history of bleeding diathesis or coagulopathy.
  • Any hemorrhage or bleeding event ≥ NCI CTCAE version 4.0 Grade 3 within 4 weeks prior to start of study medication.
  • Unwillingness to give written informed consent, unwillingness to participate, or inability to comply with the protocol for the duration of the study.
  • Active hepatitis B infection, active hepatitis C infection or known HIV carrier.
  • Patient may not have received prior chemotherapy for metastatic or unresectable disease.
  • Patients may have received prior adjuvant therapy (chemotherapy and/or chemoradiation) if more than 6 months have elapsed between the end of adjuvant therapy and registration.
  • Patient may not have received prior 5-Fluorouracil, Leucovorin, Oxaliplatin or regorafenib. Patient may have received prior radiosensitizing doses of 5Fu if more than 6 months have elapsed between the end of adjuvant therapy and registration.
  • Patient may not have had major surgical procedure within 4 weeks of registration.
  • Patient may not have had radiation within 2 weeks of registration.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01913639

Contacts
Contact: Yelena Janjigian, MD 646-888-4186
Contact: David Ilson, MD 646-888-4183

Locations
United States, New Jersey
Memoral Sloan Kettering Cancer Center Recruiting
Basking Ridge, New Jersey, United States
Contact: Yelena Janjigian, MD         
Principal Investigator: Yelena Janjigian, MD         
United States, New York
Memorial Sloan-Kettering Cancer Center @ Suffolk Recruiting
Commack, New York, United States, 11725
Contact: Yelena Janjigian, MD         
Principal Investigator: Yelena Janjigian, MD         
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Yelena Janjigian, MD    646-888-4186      
Contact: David Ilson, MD    646-888-4183      
Principal Investigator: Yelena Janjigian, MD         
Memorial Sloan-Kettering at Mercy Medical Center Recruiting
Rockville Centre, New York, United States
Contact: Yelena Janjigian, MD         
Principal Investigator: Yelena Janjigian, MD         
Memoral Sloan Kettering Cancer Center@Phelps Memorial Hospital Recruiting
Sleepy Hollow, New York, United States
Contact: Yelena Janjigian, MD         
Principal Investigator: Yelena Janjigian, MD         
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Bayer
Investigators
Principal Investigator: Yelena Janjigian, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01913639     History of Changes
Other Study ID Numbers: 13-080
Study First Received: July 29, 2013
Last Updated: July 21, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
BAY 73-4506 (REGORAFENIB)
FLUOROURACIL
LEUCOVORIN
OXALIPLATIN

Additional relevant MeSH terms:
Esophageal Neoplasms
Stomach Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Esophageal Diseases
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Head and Neck Neoplasms
Neoplasms
Neoplasms by Site
Stomach Diseases
Fluorouracil
Oxaliplatin
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014