FOLFOX Plus Regorafenib in Patients With Unresectable or Metastatic Esophagogastric Cancer

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. Read our disclaimer for details. Identifier: NCT01913639
Recruitment Status : Active, not recruiting
First Posted : August 1, 2013
Last Update Posted : April 18, 2018
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Brief Summary:
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 or disease Intervention/treatment Phase
Esophageal Cancer Gastric Cancer Drug: Regorafenib Drug: 5-Fluorouracil Drug: Leucovorin Drug: Oxaliplatin Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of FOLFOX Plus Regorafenib in Patients With Unresectable or Metastatic Esophagogastric Cancer
Study Start Date : July 2013
Estimated Primary Completion Date : July 2019
Estimated Study Completion Date : July 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Regorafenib

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. progression free survival (PFS) [ Time Frame: 6 months ]

Secondary Outcome Measures :
  1. overall survival (OS) [ Time Frame: 2 years ]
    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

  2. response rate [ Time Frame: 4 weeks ]
    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.

  3. Toxicity [ Time Frame: 2 weeks (14 days) prior to receiving study treatment (+/- 7 days) ]
    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.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

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 identifier (NCT number): NCT01913639

United States, New Jersey
Memoral Sloan Kettering Cancer Center
Basking Ridge, New Jersey, United States
United States, New York
Memorial Sloan Kettering Cancer Center @ Suffolk
Commack, New York, United States, 11725
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Memorial Sloan Kettering at Mercy Medical Center
Rockville Centre, New York, United States
Memoral Sloan Kettering Cancer Center@Phelps Memorial Hospital
Sleepy Hollow, New York, United States
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Principal Investigator: Yelena Janjigian, MD Memorial Sloan Kettering Cancer Center

Additional Information:
Responsible Party: Memorial Sloan Kettering Cancer Center Identifier: NCT01913639     History of Changes
Other Study ID Numbers: 13-080
First Posted: August 1, 2013    Key Record Dates
Last Update Posted: April 18, 2018
Last Verified: April 2018

Keywords provided by Memorial Sloan Kettering Cancer Center:

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