Trial Outcomes & Findings for Epirubicin, Oxaliplatin and Fluorouracil (EOF) in Cancer of the Esophagus, Gastroesophageal Junction, or Stomach (NCT NCT00601705)

Last Updated: 2019-04-30

Results Overview

Feasibility of induction chemoradiotherapy as measured by resectability in greater than 75% of participants. The number of participants that were resectable.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

61 participants

Primary outcome timeframe

at 12 weeks from on study

Results posted on

2019-04-30

Participant Flow

Participant milestones

Participant milestones
Measure	Epirubicin, Oxaliplatin, 5-fluorouracil, and Surgery Subjects received epirubicin (50-mg/m\^2), oxaliplatin (130-mg/m\^2), 5-fluorouracil (5FU; 200mg/m\^2/d), and surgery, which took place 4 to 5 weeks after the completion of preoperative chemotherapy. Epirubicin and oxaliplatin were given on day 1, while 5FU was intravenously infused for 21-days. Surgery was conducted 4 to 5-weeks after chemotherapy. Six to ten-weeks after surgery chemoradiotherapy was initiated. With radiotherapy, patients received two cycles of cisplatin and 5FU during the first and fourth weeks after surgery; they were administered intravenously over 96-hours. Specifically, cisplatin and 5FU total dose was 80-mg/m\^2 (20-mg/m\^2/d) and 4000 mg/m\^2 (1000-mg/m\^2/d), respectively.
Overall Study STARTED	61
Overall Study COMPLETED	60
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Epirubicin, Oxaliplatin, 5-fluorouracil, and Surgery Subjects received epirubicin (50-mg/m\^2), oxaliplatin (130-mg/m\^2), 5-fluorouracil (5FU; 200mg/m\^2/d), and surgery, which took place 4 to 5 weeks after the completion of preoperative chemotherapy. Epirubicin and oxaliplatin were given on day 1, while 5FU was intravenously infused for 21-days. Surgery was conducted 4 to 5-weeks after chemotherapy. Six to ten-weeks after surgery chemoradiotherapy was initiated. With radiotherapy, patients received two cycles of cisplatin and 5FU during the first and fourth weeks after surgery; they were administered intravenously over 96-hours. Specifically, cisplatin and 5FU total dose was 80-mg/m\^2 (20-mg/m\^2/d) and 4000 mg/m\^2 (1000-mg/m\^2/d), respectively.
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Epirubicin, Oxaliplatin and Fluorouracil (EOF) in Cancer of the Esophagus, Gastroesophageal Junction, or Stomach

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Epirubicin, Oxaliplatin, 5-fluorouracil, and Surgery n=60 Participants Subjects received epirubicin (50-mg/m\^2), oxaliplatin (130-mg/m\^2), 5-fluorouracil (5FU; 200mg/m\^2/d), and surgery, which took place 4 to 5 weeks after the completion of preoperative chemotherapy. Epirubicin and oxaliplatin were given on day 1, while 5FU was intravenously infused for 21-days. Surgery was conducted 4 to 5-weeks after chemotherapy. Six to ten-weeks after surgery chemoradiotherapy was initiated. With radiotherapy, patients received two cycles of cisplatin and 5FU during the first and fourth weeks after surgery; they were administered intravenously over 96-hours. Specifically, cisplatin and 5FU total dose was 80-mg/m\^2 (20-mg/m\^2/d) and 4000 mg/m\^2 (1000-mg/m\^2/d), respectively.
Age, Continuous	60 years n=93 Participants
Sex: Female, Male Female	3 Participants n=93 Participants
Sex: Female, Male Male	57 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	2 Participants n=93 Participants
Race (NIH/OMB) White	58 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants

PRIMARY outcome

Timeframe: at 12 weeks from on study

Population: All subjects that went on study and received treatment

Feasibility of induction chemoradiotherapy as measured by resectability in greater than 75% of participants. The number of participants that were resectable.

Outcome measures

Outcome measures
Measure	Epirubicin, Oxaliplatin, 5-fluorouracil, and Surgery n=60 Participants Subjects received epirubicin (50-mg/m\^2), oxaliplatin (130-mg/m\^2), 5-fluorouracil (5FU; 200mg/m\^2/d), and surgery, which took place 4 to 5 weeks after the completion of preoperative chemotherapy. Epirubicin and oxaliplatin were given on day 1, while 5FU was intravenously infused for 21-days. Surgery was conducted 4 to 5-weeks after chemotherapy. Six to ten-weeks after surgery chemoradiotherapy was initiated. With radiotherapy, patients received two cycles of cisplatin and 5FU during the first and fourth weeks after surgery; they were administered intravenously over 96-hours. Specifically, cisplatin and 5FU total dose was 80-mg/m\^2 (20-mg/m\^2/d) and 4000 mg/m\^2 (1000-mg/m\^2/d), respectively.
Feasibility of Induction Chemoradiotherapy as Measured by Resectability Rate	54 Participants

SECONDARY outcome

Timeframe: at 12 weeks from on study

Population: Participants that complete induction therapy

Percent of participants with a clinical response: Complete clinical response is defined as the complete disappearance of all clinical evidence of tumor. Partial clinical response is defined as any improvement in the clinically determined T or N stage (without reciprocal deterioration in N or T) or a resolution of M1a disease, when compared to the pretreatment clinical stage. A partial response will not be defined based only on shrinkage of a measurable lesion unless there is improvement in the TNM stage. Stable clinical disease is defined as no change in the clinical TNM stage when compared to the pretreatment clinical stage. Progressive clinical disease is defined as any increase in the T or N stage irrespective of any reciprocal improvement in N or T, or as the development of new areas of malignancy or metastases.

Outcome measures

Outcome measures
Measure	Epirubicin, Oxaliplatin, 5-fluorouracil, and Surgery n=58 Participants Subjects received epirubicin (50-mg/m\^2), oxaliplatin (130-mg/m\^2), 5-fluorouracil (5FU; 200mg/m\^2/d), and surgery, which took place 4 to 5 weeks after the completion of preoperative chemotherapy. Epirubicin and oxaliplatin were given on day 1, while 5FU was intravenously infused for 21-days. Surgery was conducted 4 to 5-weeks after chemotherapy. Six to ten-weeks after surgery chemoradiotherapy was initiated. With radiotherapy, patients received two cycles of cisplatin and 5FU during the first and fourth weeks after surgery; they were administered intravenously over 96-hours. Specifically, cisplatin and 5FU total dose was 80-mg/m\^2 (20-mg/m\^2/d) and 4000 mg/m\^2 (1000-mg/m\^2/d), respectively.
Clinical Response Rate Complete response	0 percentage of participants
Clinical Response Rate Partial response	48 percentage of participants
Clinical Response Rate Stable disease	33 percentage of participants
Clinical Response Rate Progressive disease	19 percentage of participants

SECONDARY outcome

Timeframe: after completion of study at 35 weeks

Population: Participants that complete induction therapy

Percent of participants with a clinical response: Complete pathologic response is defined as the complete disappearance of all viable tumor in the surgical specimen. Partial pathologic response is defined as any improvement in the pathologically determined T or N stage (without reciprocal deterioration in N or T) or a resolution of M1a disease, when compared to the pretreatment esophageal ultrasound-determined clinical stage. A partial response will not be defined based only on shrinkage of a measurable lesion unless there is improvement in the TNM stage. Stable pathologic disease is defined as no change in the pathologically determined TNM stage when compared to the pretreatment esophageal ultrasound. Progressive pathologic disease is defined as any increase in the T or N stage irrespective of any reciprocal improvement in N or T, or as the development of new areas of malignancy or metastases.

Outcome measures

Outcome measures
Measure	Epirubicin, Oxaliplatin, 5-fluorouracil, and Surgery n=58 Participants Subjects received epirubicin (50-mg/m\^2), oxaliplatin (130-mg/m\^2), 5-fluorouracil (5FU; 200mg/m\^2/d), and surgery, which took place 4 to 5 weeks after the completion of preoperative chemotherapy. Epirubicin and oxaliplatin were given on day 1, while 5FU was intravenously infused for 21-days. Surgery was conducted 4 to 5-weeks after chemotherapy. Six to ten-weeks after surgery chemoradiotherapy was initiated. With radiotherapy, patients received two cycles of cisplatin and 5FU during the first and fourth weeks after surgery; they were administered intravenously over 96-hours. Specifically, cisplatin and 5FU total dose was 80-mg/m\^2 (20-mg/m\^2/d) and 4000 mg/m\^2 (1000-mg/m\^2/d), respectively.
Pathological Response Rate Complete response	3 participants
Pathological Response Rate Partial response	21 participants
Pathological Response Rate Stable disease	14 participants
Pathological Response Rate Progressive disease	20 participants

SECONDARY outcome

Timeframe: at 3 years from on study

Population: All patients that went on study

Percent of participants with a 3-year survival. A survival rate greater than 50% would suggest efficacy and justify further study.

Outcome measures

Outcome measures
Measure	Epirubicin, Oxaliplatin, 5-fluorouracil, and Surgery n=60 Participants Subjects received epirubicin (50-mg/m\^2), oxaliplatin (130-mg/m\^2), 5-fluorouracil (5FU; 200mg/m\^2/d), and surgery, which took place 4 to 5 weeks after the completion of preoperative chemotherapy. Epirubicin and oxaliplatin were given on day 1, while 5FU was intravenously infused for 21-days. Surgery was conducted 4 to 5-weeks after chemotherapy. Six to ten-weeks after surgery chemoradiotherapy was initiated. With radiotherapy, patients received two cycles of cisplatin and 5FU during the first and fourth weeks after surgery; they were administered intravenously over 96-hours. Specifically, cisplatin and 5FU total dose was 80-mg/m\^2 (20-mg/m\^2/d) and 4000 mg/m\^2 (1000-mg/m\^2/d), respectively.
Overall Survival	47 percentage of participants

SECONDARY outcome

Timeframe: at 3 years from on study

Population: All participants that went on study

A distant metastatic control rate of greater than 55 % would suggest efficacy for this treatment protocol. A locoregional control rate of less than 75% would suggest inefficacy. Locoregional control (LRC) defined by recurrence at the primary site or in regional lymph nodes and distant metastatic control (DMC), defined by recurrence in a distant site.

Outcome measures

Outcome measures
Measure	Epirubicin, Oxaliplatin, 5-fluorouracil, and Surgery n=60 Participants Subjects received epirubicin (50-mg/m\^2), oxaliplatin (130-mg/m\^2), 5-fluorouracil (5FU; 200mg/m\^2/d), and surgery, which took place 4 to 5 weeks after the completion of preoperative chemotherapy. Epirubicin and oxaliplatin were given on day 1, while 5FU was intravenously infused for 21-days. Surgery was conducted 4 to 5-weeks after chemotherapy. Six to ten-weeks after surgery chemoradiotherapy was initiated. With radiotherapy, patients received two cycles of cisplatin and 5FU during the first and fourth weeks after surgery; they were administered intravenously over 96-hours. Specifically, cisplatin and 5FU total dose was 80-mg/m\^2 (20-mg/m\^2/d) and 4000 mg/m\^2 (1000-mg/m\^2/d), respectively.
Locoregional Control and Distant Metastatic Control Locoregional Control	4 Participants
Locoregional Control and Distant Metastatic Control Distant Metastatic Control	29 Participants

SECONDARY outcome

Timeframe: Between 6 to 10 weeks postoperatively

Population: All patients that went on study

Ability to complete postoperative chemoradiotherapy. A threshold level of 65% was set and if less than this percentage completed the phase, it would be deemed unacceptable. The anticipation was that 53-patients would be evaluable for this end point.

Outcome measures

Outcome measures
Measure	Epirubicin, Oxaliplatin, 5-fluorouracil, and Surgery n=60 Participants Subjects received epirubicin (50-mg/m\^2), oxaliplatin (130-mg/m\^2), 5-fluorouracil (5FU; 200mg/m\^2/d), and surgery, which took place 4 to 5 weeks after the completion of preoperative chemotherapy. Epirubicin and oxaliplatin were given on day 1, while 5FU was intravenously infused for 21-days. Surgery was conducted 4 to 5-weeks after chemotherapy. Six to ten-weeks after surgery chemoradiotherapy was initiated. With radiotherapy, patients received two cycles of cisplatin and 5FU during the first and fourth weeks after surgery; they were administered intravenously over 96-hours. Specifically, cisplatin and 5FU total dose was 80-mg/m\^2 (20-mg/m\^2/d) and 4000 mg/m\^2 (1000-mg/m\^2/d), respectively.
Postoperative Adjuvant Chemoradiotherapy Feasibility	48 Participants

Adverse Events

Epirubicin, Oxaliplatin and Fluorouracil

Serious events: 24 serious events

Other events: 60 other events

Deaths: 41 deaths

Serious adverse events

Serious adverse events
Measure	Epirubicin, Oxaliplatin and Fluorouracil n=60 participants at risk cisplatin: 20 mg/m2/day IV continuous infusion over 24 hours for 96 hours. epirubicin hydrochloride: 50 mg/m2 IV bolus fluorouracil: 200 mg/m2/day continuous infusion for all 9 weeks, beginning on day 1. oxaliplatin: 130 mg/m2 IV infusion over 2 hours adjuvant therapy: At 6-10 weeks after surgery patients will begin postoperative chemoradiotherapy. Daily radiation therapy fractions of 180-200 cGy will be given. Concurrent with this radiation, two cycles of chemotherapy will be given, during the first and fourth weeks of the radiation neoadjuvant therapy: Three weeks after discontinuing the fluorouracil patients will be fully restaged to assess for a clinical response, and to ensure that there is no contraindication to surgical resection, which will be scheduled for app
Gastrointestinal disorders Dehydration	3.3% 2/60 • Number of events 2 • Participants were followed for adverse events while on study, treatment and the 30 days following treatment discontinuation over a period of up to 1 year. Adverse events were reported separately for pre-operative therapy (60 participants) and post-operative therapy (48 participants).
Gastrointestinal disorders Diarrhea	10.0% 6/60 • Number of events 11 • Participants were followed for adverse events while on study, treatment and the 30 days following treatment discontinuation over a period of up to 1 year. Adverse events were reported separately for pre-operative therapy (60 participants) and post-operative therapy (48 participants).
Gastrointestinal disorders Dysphagia	1.7% 1/60 • Number of events 2 • Participants were followed for adverse events while on study, treatment and the 30 days following treatment discontinuation over a period of up to 1 year. Adverse events were reported separately for pre-operative therapy (60 participants) and post-operative therapy (48 participants).
Gastrointestinal disorders Enteritis - inflammation of the small bowel	3.3% 2/60 • Number of events 2 • Participants were followed for adverse events while on study, treatment and the 30 days following treatment discontinuation over a period of up to 1 year. Adverse events were reported separately for pre-operative therapy (60 participants) and post-operative therapy (48 participants).
Gastrointestinal disorders Fistula, GI - Stomach	1.7% 1/60 • Number of events 1 • Participants were followed for adverse events while on study, treatment and the 30 days following treatment discontinuation over a period of up to 1 year. Adverse events were reported separately for pre-operative therapy (60 participants) and post-operative therapy (48 participants).
Gastrointestinal disorders Mucositis/stomatitis - oral cavity	1.7% 1/60 • Number of events 1 • Participants were followed for adverse events while on study, treatment and the 30 days following treatment discontinuation over a period of up to 1 year. Adverse events were reported separately for pre-operative therapy (60 participants) and post-operative therapy (48 participants).
Gastrointestinal disorders Nausea	6.7% 4/60 • Number of events 9 • Participants were followed for adverse events while on study, treatment and the 30 days following treatment discontinuation over a period of up to 1 year. Adverse events were reported separately for pre-operative therapy (60 participants) and post-operative therapy (48 participants).
Gastrointestinal disorders Vomiting	6.7% 4/60 • Number of events 9 • Participants were followed for adverse events while on study, treatment and the 30 days following treatment discontinuation over a period of up to 1 year. Adverse events were reported separately for pre-operative therapy (60 participants) and post-operative therapy (48 participants).
Hepatobiliary disorders Cholecystitis	1.7% 1/60 • Number of events 1 • Participants were followed for adverse events while on study, treatment and the 30 days following treatment discontinuation over a period of up to 1 year. Adverse events were reported separately for pre-operative therapy (60 participants) and post-operative therapy (48 participants).
Infections and infestations Colitis, infectious	1.7% 1/60 • Number of events 1 • Participants were followed for adverse events while on study, treatment and the 30 days following treatment discontinuation over a period of up to 1 year. Adverse events were reported separately for pre-operative therapy (60 participants) and post-operative therapy (48 participants).
Nervous system disorders Neuropathy	1.7% 1/60 • Number of events 1 • Participants were followed for adverse events while on study, treatment and the 30 days following treatment discontinuation over a period of up to 1 year. Adverse events were reported separately for pre-operative therapy (60 participants) and post-operative therapy (48 participants).
Nervous system disorders Syncope	1.7% 1/60 • Number of events 1 • Participants were followed for adverse events while on study, treatment and the 30 days following treatment discontinuation over a period of up to 1 year. Adverse events were reported separately for pre-operative therapy (60 participants) and post-operative therapy (48 participants).
Vascular disorders Thrombosis	3.3% 2/60 • Number of events 3 • Participants were followed for adverse events while on study, treatment and the 30 days following treatment discontinuation over a period of up to 1 year. Adverse events were reported separately for pre-operative therapy (60 participants) and post-operative therapy (48 participants).

Other adverse events

Other adverse events
Measure	Epirubicin, Oxaliplatin and Fluorouracil n=60 participants at risk cisplatin: 20 mg/m2/day IV continuous infusion over 24 hours for 96 hours. epirubicin hydrochloride: 50 mg/m2 IV bolus fluorouracil: 200 mg/m2/day continuous infusion for all 9 weeks, beginning on day 1. oxaliplatin: 130 mg/m2 IV infusion over 2 hours adjuvant therapy: At 6-10 weeks after surgery patients will begin postoperative chemoradiotherapy. Daily radiation therapy fractions of 180-200 cGy will be given. Concurrent with this radiation, two cycles of chemotherapy will be given, during the first and fourth weeks of the radiation neoadjuvant therapy: Three weeks after discontinuing the fluorouracil patients will be fully restaged to assess for a clinical response, and to ensure that there is no contraindication to surgical resection, which will be scheduled for app
Respiratory, thoracic and mediastinal disorders Chylothorax	16.7% 8/48 • Participants were followed for adverse events while on study, treatment and the 30 days following treatment discontinuation over a period of up to 1 year. Adverse events were reported separately for pre-operative therapy (60 participants) and post-operative therapy (48 participants).
Respiratory, thoracic and mediastinal disorders pneumonia	16.7% 8/48 • Participants were followed for adverse events while on study, treatment and the 30 days following treatment discontinuation over a period of up to 1 year. Adverse events were reported separately for pre-operative therapy (60 participants) and post-operative therapy (48 participants).
Injury, poisoning and procedural complications wound infections	20.8% 10/48 • Participants were followed for adverse events while on study, treatment and the 30 days following treatment discontinuation over a period of up to 1 year. Adverse events were reported separately for pre-operative therapy (60 participants) and post-operative therapy (48 participants).
Skin and subcutaneous tissue disorders Hand-foot syndrome	18.8% 9/48 • Participants were followed for adverse events while on study, treatment and the 30 days following treatment discontinuation over a period of up to 1 year. Adverse events were reported separately for pre-operative therapy (60 participants) and post-operative therapy (48 participants).
Blood and lymphatic system disorders Neutropenia	27.1% 13/48 • Participants were followed for adverse events while on study, treatment and the 30 days following treatment discontinuation over a period of up to 1 year. Adverse events were reported separately for pre-operative therapy (60 participants) and post-operative therapy (48 participants).
Blood and lymphatic system disorders Febrile neutropenia	10.4% 5/48 • Participants were followed for adverse events while on study, treatment and the 30 days following treatment discontinuation over a period of up to 1 year. Adverse events were reported separately for pre-operative therapy (60 participants) and post-operative therapy (48 participants).
Blood and lymphatic system disorders Platelets <50,000/μl	20.8% 10/48 • Participants were followed for adverse events while on study, treatment and the 30 days following treatment discontinuation over a period of up to 1 year. Adverse events were reported separately for pre-operative therapy (60 participants) and post-operative therapy (48 participants).

Additional Information

Dr. David Adelstein

Cleveland Clinic

Phone: 216 444-9310

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place