Esophageal Cancer, Gastric Cancer
Conditions
Keywords
BAY 73-4506 (REGORAFENIB), FLUOROURACIL, LEUCOVORIN, OXALIPLATIN
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.
Interventions
DRUGRegorafenib
DRUG5-Fluorouracil
DRUGLeucovorin
DRUGOxaliplatin
Sponsors
Bayer
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression Free Survival (PFS) | 6 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | 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 |
| Overall Response Rate | 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. |
| Participants Evaluated for Toxicity | 1 year | Adverse events will be determined as per the NCI Common Toxicity Criteria, version 4.0. Toxicity during cycle 1 and subsequent cycles will be reported. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 39 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Not Eligible | 3 |
Baseline characteristics
| Characteristic | FOLFOX Plus Regorafenib |
|---|---|
| Age, Continuous | 58 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 36 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 31 Participants |
| Region of Enrollment United States | 39 Participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 30 / 39 |
| other Total, other adverse events | 36 / 39 |
| serious Total, serious adverse events | 17 / 39 |
Outcome results
Primary
Progression Free Survival (PFS)
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FOLFOX Plus Regorafenib | Progression Free Survival (PFS) | 53 percentage of participants |
Secondary
Overall Response Rate
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.
Time frame: 4 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FOLFOX Plus Regorafenib | Overall Response Rate | 54 percentage of participants with CR or PR |
Secondary
Overall Survival (OS)
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
Time frame: 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FOLFOX Plus Regorafenib | Overall Survival (OS) | 14.2 months |
Secondary
Participants Evaluated for Toxicity
Adverse events will be determined as per the NCI Common Toxicity Criteria, version 4.0. Toxicity during cycle 1 and subsequent cycles will be reported.
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| FOLFOX Plus Regorafenib | Participants Evaluated for Toxicity | 39 Participants |