Trial Outcomes & Findings for FOLFOX Plus Regorafenib in Patients With Unresectable or Metastatic Esophagogastric Cancer (NCT NCT01913639)
NCT ID: NCT01913639
Last Updated: 2020-05-15
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
39 participants
Primary outcome timeframe
6 months
Results posted on
2020-05-15
Participant Flow
Participant milestones
| Measure |
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.
|
|---|---|
|
Overall Study
STARTED
|
39
|
|
Overall Study
COMPLETED
|
36
|
|
Overall Study
NOT COMPLETED
|
3
|
Reasons for withdrawal
| Measure |
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.
|
|---|---|
|
Overall Study
Not Eligible
|
3
|
Baseline Characteristics
FOLFOX Plus Regorafenib in Patients With Unresectable or Metastatic Esophagogastric Cancer
Baseline characteristics by cohort
| Measure |
FOLFOX Plus Regorafenib
n=39 Participants
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.
|
|---|---|
|
Age, Continuous
|
58 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
32 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
36 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
31 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
39 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 6 monthsOutcome measures
| Measure |
FOLFOX Plus Regorafenib
n=39 Participants
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.
|
|---|---|
|
Progression Free Survival (PFS)
|
53 percentage of participants
Interval 38.0 to 71.0
|
SECONDARY outcome
Timeframe: 2 yearsOverall survival will be measured from the start of treatment to death or last follow-up and will be estimated using the Kaplan-Meier method
Outcome measures
| Measure |
FOLFOX Plus Regorafenib
n=39 Participants
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.
|
|---|---|
|
Overall Survival (OS)
|
14.2 months
Interval 8.1 to 20.7
|
SECONDARY outcome
Timeframe: 4 weeksThis 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.
Outcome measures
| Measure |
FOLFOX Plus Regorafenib
n=39 Participants
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.
|
|---|---|
|
Overall Response Rate
|
54 percentage of participants with CR or PR
Interval 37.0 to 70.0
|
SECONDARY outcome
Timeframe: 1 yearAdverse events will be determined as per the NCI Common Toxicity Criteria, version 4.0. Toxicity during cycle 1 and subsequent cycles will be reported.
Outcome measures
| Measure |
FOLFOX Plus Regorafenib
n=39 Participants
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.
|
|---|---|
|
Participants Evaluated for Toxicity
|
39 Participants
|
Adverse Events
FOLFOX Plus Regorafenib
Serious events: 17 serious events
Other events: 36 other events
Deaths: 30 deaths
Serious adverse events
| Measure |
FOLFOX Plus Regorafenib
n=39 participants at risk
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.
|
|---|---|
|
Gastrointestinal disorders
Abdominal distension
|
7.7%
3/39 • 1 year
|
|
Gastrointestinal disorders
Abdominal pain
|
23.1%
9/39 • 1 year
|
|
Renal and urinary disorders
Acute kidney injury
|
2.6%
1/39 • 1 year
|
|
Investigations
Alanine aminotransferase increased
|
2.6%
1/39 • 1 year
|
|
Investigations
Alkaline phosphatase increased
|
2.6%
1/39 • 1 year
|
|
Metabolism and nutrition disorders
Anorexia
|
7.7%
3/39 • 1 year
|
|
Investigations
Aspartate aminotransferase increased
|
2.6%
1/39 • 1 year
|
|
Cardiac disorders
Atrial fibrillation
|
2.6%
1/39 • 1 year
|
|
Investigations
Blood bilirubin increased
|
2.6%
1/39 • 1 year
|
|
Cardiac disorders
Chest pain - cardiac
|
2.6%
1/39 • 1 year
|
|
Gastrointestinal disorders
Constipation
|
12.8%
5/39 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
2.6%
1/39 • 1 year
|
|
General disorders
Death NOS
|
2.6%
1/39 • 1 year
|
|
Metabolism and nutrition disorders
Dehydration
|
5.1%
2/39 • 1 year
|
|
Gastrointestinal disorders
Diarrhea
|
2.6%
1/39 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
10.3%
4/39 • 1 year
|
|
General disorders
Fatigue
|
7.7%
3/39 • 1 year
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
2.6%
1/39 • 1 year
|
|
General disorders
Fever
|
10.3%
4/39 • 1 year
|
|
Gastrointestinal disorders
Gastrointestinal disorders -Other, specify
|
5.1%
2/39 • 1 year
|
|
Vascular disorders
Hypertension
|
2.6%
1/39 • 1 year
|
|
Vascular disorders
Hypotension
|
5.1%
2/39 • 1 year
|
|
Cardiac disorders
Left ventricular systolic dysfunction
|
2.6%
1/39 • 1 year
|
|
Investigations
Lipase increased
|
2.6%
1/39 • 1 year
|
|
Nervous system disorders
Muscle weakness left-sided
|
2.6%
1/39 • 1 year
|
|
Gastrointestinal disorders
Nausea
|
7.7%
3/39 • 1 year
|
|
Investigations
Neutrophil count decreased
|
5.1%
2/39 • 1 year
|
|
General disorders
Non-cardiac chest pain
|
2.6%
1/39 • 1 year
|
|
General disorders
Pain
|
2.6%
1/39 • 1 year
|
|
Nervous system disorders
Paresthesia
|
2.6%
1/39 • 1 year
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
2.6%
1/39 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
7.7%
3/39 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
2.6%
1/39 • 1 year
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
2.6%
1/39 • 1 year
|
|
Cardiac disorders
Right ventricular dysfunction
|
2.6%
1/39 • 1 year
|
|
Investigations
Serum amylase increased
|
2.6%
1/39 • 1 year
|
|
Cardiac disorders
Sinus tachycardia
|
5.1%
2/39 • 1 year
|
|
Skin and subcutaneous tissue disorders
Skin & subcutaneous tissue disorders Other, spec
|
2.6%
1/39 • 1 year
|
|
Gastrointestinal disorders
Small intestinal perforation
|
2.6%
1/39 • 1 year
|
|
Nervous system disorders
Syncope
|
5.1%
2/39 • 1 year
|
|
Vascular disorders
Thromboembolic event
|
5.1%
2/39 • 1 year
|
|
Cardiac disorders
Ventricular tachycardia
|
2.6%
1/39 • 1 year
|
|
Gastrointestinal disorders
Vomiting
|
10.3%
4/39 • 1 year
|
|
Investigations
Weight loss
|
2.6%
1/39 • 1 year
|
Other adverse events
| Measure |
FOLFOX Plus Regorafenib
n=39 participants at risk
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.
|
|---|---|
|
General disorders
Fatigue
|
79.5%
31/39 • 1 year
|
|
Blood and lymphatic system disorders
Anemia
|
71.8%
28/39 • 1 year
|
|
Investigations
White blood cell decreased
|
71.8%
28/39 • 1 year
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
69.2%
27/39 • 1 year
|
|
Investigations
Platelet count decreased
|
69.2%
27/39 • 1 year
|
|
Vascular disorders
Hypertension
|
64.1%
25/39 • 1 year
|
|
Gastrointestinal disorders
Nausea
|
59.0%
23/39 • 1 year
|
|
Investigations
Neutrophil count decreased
|
59.0%
23/39 • 1 year
|
|
Investigations
Alanine aminotransferase increased
|
53.8%
21/39 • 1 year
|
|
Investigations
Aspartate aminotransferase increased
|
51.3%
20/39 • 1 year
|
|
Gastrointestinal disorders
Mucositis oral
|
35.9%
14/39 • 1 year
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysesthesia syndrome
|
35.9%
14/39 • 1 year
|
|
Investigations
Alkaline phosphatase increased
|
33.3%
13/39 • 1 year
|
|
Metabolism and nutrition disorders
Anorexia
|
30.8%
12/39 • 1 year
|
|
Gastrointestinal disorders
Diarrhea
|
30.8%
12/39 • 1 year
|
|
Gastrointestinal disorders
Constipation
|
28.2%
11/39 • 1 year
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
28.2%
11/39 • 1 year
|
|
Gastrointestinal disorders
Vomiting
|
25.6%
10/39 • 1 year
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
23.1%
9/39 • 1 year
|
|
Investigations
Weight loss
|
23.1%
9/39 • 1 year
|
|
Investigations
Blood bilirubin increased
|
20.5%
8/39 • 1 year
|
|
Metabolism and nutrition disorders
Hyponatremia
|
17.9%
7/39 • 1 year
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
15.4%
6/39 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
15.4%
6/39 • 1 year
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
15.4%
6/39 • 1 year
|
|
Gastrointestinal disorders
Abdominal pain
|
10.3%
4/39 • 1 year
|
|
General disorders
Edema limbs
|
10.3%
4/39 • 1 year
|
|
Investigations
Lymphocyte count decreased
|
10.3%
4/39 • 1 year
|
|
Nervous system disorders
Paresthesia
|
10.3%
4/39 • 1 year
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
10.3%
4/39 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
7.7%
3/39 • 1 year
|
|
Gastrointestinal disorders
Dysphagia
|
7.7%
3/39 • 1 year
|
|
General disorders
Fever
|
7.7%
3/39 • 1 year
|
|
Nervous system disorders
Headache
|
7.7%
3/39 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Hoarseness
|
7.7%
3/39 • 1 year
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
7.7%
3/39 • 1 year
|
|
Metabolism and nutrition disorders
Hypokalemia
|
7.7%
3/39 • 1 year
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
7.7%
3/39 • 1 year
|
|
Nervous system disorders
Dizziness
|
5.1%
2/39 • 1 year
|
|
Gastrointestinal disorders
Dry mouth
|
5.1%
2/39 • 1 year
|
|
Nervous system disorders
Dysgeusia
|
5.1%
2/39 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
5.1%
2/39 • 1 year
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
5.1%
2/39 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
5.1%
2/39 • 1 year
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
5.1%
2/39 • 1 year
|
|
Investigations
INR increased
|
5.1%
2/39 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
5.1%
2/39 • 1 year
|
|
General disorders
Pain
|
5.1%
2/39 • 1 year
|
|
Skin and subcutaneous tissue disorders
Skin hyperpigmentation
|
5.1%
2/39 • 1 year
|
|
Gastrointestinal disorders
Small intestinal mucositis
|
5.1%
2/39 • 1 year
|
Additional Information
Dr. Yelena Janjigian, MD
Memorial Sloan Kettering Cancer Center
Phone: 646-888-4186
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place