Docetaxel, Oxaliplatin, Capecitabine, Fluorouracil, and Radiation Therapy in Treating Patients With Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction

• Sponsor: Alliance for Clinical Trials in Oncology (Other)
• Overall Status: Completed
• CT.gov ID: NCT00938470
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 73
• Locations: 187
• Arms: 2
• Duration (Months): 97.9
• Patients Per Site: 0.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This randomized phase II trial studies how well docetaxel, oxaliplatin, capecitabine, fluorouracil, and radiation therapy works compared with fluorouracil when given together with oxaliplatin and radiation therapy in treating patients with cancer of the esophagus or gastroesophageal junction that has spread from where it started to nearby tissue or lymph nodes. Drugs used in chemotherapy, such as docetaxel, oxaliplatin, capecitabine, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving more than one drug (combination chemotherapy) together with radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Condition or Disease	Intervention/Treatment	Phase
Adenocarcinoma of the Gastroesophageal Junction; Esophageal Cancer; Gastric Cancer	Drug: capecitabine; Drug: docetaxel; Drug: fluorouracil; Drug: oxaliplatin; Radiation: radiation therapy; Procedure: therapeutic conventional surgery	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To assess and compare the pathologic complete response (PCR) rate of patients in Arm A receiving the sequence docetaxel, oxaliplatin, and capecitabine (DOC) followed by 5-fluorouracil (5-FU), oxaliplatin, and radiation therapy (RT) with patients in Arm B receiving only 5-FU, oxaliplatin and RT in patients with potentially resectable adenocarcinoma (ACA) of the esophagus, gastroesophageal junction (GEJ), or gastric cardia.

SECONDARY OBJECTIVES:

1. To assess the adverse event (AE) profile and safety of the proposed treatment in this population.

2. To assess and compare the overall survival (OS) between treatment arms. III. To assess and compare the disease-free survival between treatment arms. IV. To assess and compare the clinical tumor response rate of the proposed regiments when administered before surgery between treatment arms.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive docetaxel intravenously (IV) over 1 hour and oxaliplatin IV over 2 hours on day 1. Patients also receive capecitabine orally (PO) twice daily (BID) on days 1-14. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. After completion of the second course, patients receive fluorouracil* IV continuously on days 1-5 and oxaliplatin IV over 2 hours on days 1, 15, and 29. Patients also undergo radiotherapy** 5 days a week for 5.5 weeks in the absence of disease progression or unacceptable toxicity. Approximately 4-12 weeks after completion of radiotherapy, patients undergo surgery.

ARM II: Patients receive fluorouracil IV continuously on days 1-5 and oxaliplatin IV over 2 hours on days 1, 15, and 29. Patients also undergo radiotherapy and then surgery as in Arm I.

• NOTE: * Fluorouracil continuous IV infusion begins within 24 hours of radiotherapy and ends within 24 hours of radiotherapy completion.

• NOTE: ** Radiotherapy should begin within 2-6 weeks after completion of 2 courses of docetaxel, oxaliplatin, and capecitabine.

After completion of study treatment, patients are followed up every 3 months for 2 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 73 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized Phase II Trial of Extended Neoadjuvant Therapy for Locally Advanced Adenocarcinoma of the Esophagus, Gastroesophageal Junction, and Gastric Cardia
• Study Start Date: Jan 1, 2010
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: Mar 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (combination chemotherapy, radiation therapy, surgery) Patients receive docetaxel IV over 1 hour and oxaliplatin IV over 2 hours on day 1. Patients also receive capecitabine PO BID on days 1-14. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. After completion of the second course, patients receive fluorouracil IV continuously on days 1-5 and oxaliplatin IV over 2 hours on days 1, 15, and 29. Patients also undergo radiotherapy 5 days a week for 5.5 weeks in the absence of disease progression or unacceptable toxicity. Approximately 4-12 weeks after completion of radiotherapy, patients undergo surgery.	Drug: capecitabine; Given PO; Drug: docetaxel; Given IV; Drug: fluorouracil; Given IV; Drug: oxaliplatin; Given IV; Radiation: radiation therapy; Undergo radiation therapy; Procedure: therapeutic conventional surgery; Undergo surgery
Active Comparator: Arm II (oxaliplatin, fluorouracil, radiation, and surgery) Patients receive fluorouracil IV continuously on days 1-5 and oxaliplatin IV over 2 hours on days 1, 15, and 29. Patients also undergo radiotherapy and then surgery as in Arm I.	Drug: fluorouracil; Given IV; Drug: oxaliplatin; Given IV; Radiation: radiation therapy; Undergo radiation therapy; Procedure: therapeutic conventional surgery; Undergo surgery

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Pathologic Complete Response (PCR) [Up to 2 years]

   Pathologic complete response was defined as no gross or microscopic tumor identified with the surgical specimen. All lymph nodes should be free of tumor to document a PCR. If no gross tumor is visible, section around the area of inflammation (nodularity) should be made every 2-3 cm and specimens examined.

Secondary Outcome Measures

1. Overall Survival [Up to 2 years]

   Overall survival was defined as the time from randomization to the time of death from any cause. Overall survival was censored at the date of last follow-up visit for patients who are still alive or loss of follow-up.

2. Disease-free Survival [Up to 2 years]

   Disease-free survival was defined as the time from randomization to the date of recurrent or death, whichever comes first.

3. Number of Participants Who Experienced a Maximum Grade of 3 or Above Adverse Event [Up to 2 years]

   Adverse events were assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

4. Percentage of Participants With Overall Clinical Tumor Response (CR or PR) [Up to 2 years]

   Overall clinical tumor response rate was defined as the percentage of evaluable participants who achieved either complete response (CR) or partial response (PR) noted on the objective status from pre-surgical staging (for arm II) or either from pre-RT or pre-surgical staging (for arm I).> CR was defined as disappearance of all non-target lesion (TL) and normalization of tumor biomarker level, all lymph nodes (LN) must be non-pathological in size (<1 cm short axis); or disappearance of all TL and normalization of tumor biomarkers, any pathological LN (whether target or non-target) must have reduction in short axis to <1 cm; or >=30% decrease in the sum of the diameters of TL taking as reference the baseline sum of the diameters.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria

• Histological confirmation of adenocarcinoma of the esophagus, gastroesophageal (GE) junction, or gastric cardia

• Tumor must be considered surgically resectable; Note: patients with T4N0M0 tumors that are potentially resectable are also eligible

• Nodal involvement: patients with involvement of celiac nodes, (stations 15-20) are eligible if the primary lesion is mid-thoracic, distal esophagus or GE junction; patients with supraclavicular node involvement are eligible with upper thoracic esophagus primary lesions

• Capable of swallowing pills

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2

• Absolute neutrophil count (ANC) >= 1500

• Peripheral platelet count >= 100,000

• Hemoglobin >= 9.0 g/dL

• Total bilirubin =< 1.5 x upper normal limit (UNL)

• Serum glutamic oxaloacetic transaminase (SGOT) (alanine aminotransferase [AST]) =< 3 x UNL

• Creatinine =< 1.5 x UNL

• Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only

• Provide informed written consent

• Willingness to return to NCCTG enrolling institution for follow-up

• Patient willing to provide mandatory tissue and blood samples for research purposes

• Patient willing to allow use of FDG PET/CT scans for mandatory research purposes

Exclusion Criteria

• Evidence of distant metastases

• Palpable supraclavicular nodes, biopsy-proven involvement of supraclavicular nodes, or radiographically involved supraclavicular nodes (> 1.5 cm in greatest dimension) for lesions in mid-thoracic, distal thoracic or GE junction

• T1N0M0 or T2N0M0 tumor stage

• Any of the following

• Pregnant women

• Nursing women

• Men or women of childbearing potential who are unwilling to employ adequate contraception

• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens

• Immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be human immunodeficiency virus (HIV) positive

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Uncontrolled diabetes (i.e., will interfere with the performance of the FDG PET/CT scans)

• Receiving current treatment or prior treatment for this malignancy

• Other active malignancy 5 years prior to registration, except non-melanotic skin cancer or carcinoma-in-situ of the cervix; if there is a history of prior malignancy, patient must not be receiving other specific treatment (other than hormonal therapy) for cancer

• Prior radiation to > 30% of the marrow cavity

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Scottsdale	Scottsdale	Arizona	United States	85259-5499
2	Poudre Valley Hospital	Fort Collins	Colorado	United States	80524
3	Front Range Cancer Specialists	Fort Collins	Colorado	United States	80528
4	Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center	Hartford	Connecticut	United States	06105
5	Mayo Clinic - Jacksonville	Jacksonville	Florida	United States	32224
6	Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center	Boise	Idaho	United States	83706
7	Illinois CancerCare - Bloomington	Bloomington	Illinois	United States	61701
8	St. Joseph Medical Center	Bloomington	Illinois	United States	61701
9	Graham Hospital	Canton	Illinois	United States	61520
10	Illinois CancerCare - Canton	Canton	Illinois	United States	61520
11	Illinois CancerCare - Carthage	Carthage	Illinois	United States	62321
12	Eureka Community Hospital	Eureka	Illinois	United States	61530
13	Illinois CancerCare - Eureka	Eureka	Illinois	United States	61530
14	Galesburg Clinic, PC	Galesburg	Illinois	United States	61401
15	Illinois CancerCare - Galesburg	Galesburg	Illinois	United States	61401
16	Illinois CancerCare - Havana	Havana	Illinois	United States	62644
17	Mason District Hospital	Havana	Illinois	United States	62644
18	Illinois CancerCare - Kewanee Clinic	Kewanee	Illinois	United States	61443
19	Illinois CancerCare - Macomb	Macomb	Illinois	United States	61455
20	McDonough District Hospital	Macomb	Illinois	United States	61455
21	Trinity Cancer Center at Trinity Medical Center - 7th Street Campus	Moline	Illinois	United States	61265
22		Moline	Illinois	United States	61265
23	Illinois CancerCare - Monmouth	Monmouth	Illinois	United States	61462
24	OSF Holy Family Medical Center	Monmouth	Illinois	United States	61462
25	BroMenn Regional Medical Center	Normal	Illinois	United States	61761
26	Community Cancer Center	Normal	Illinois	United States	61761
27	Illinois CancerCare - Community Cancer Center	Normal	Illinois	United States	61761
28	Community Hospital of Ottawa	Ottawa	Illinois	United States	61350
29	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois	United States	61350
30	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois	United States	61554
31	CCOP - Illinois Oncology Research Association	Peoria	Illinois	United States	61615
32	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois	United States	61615
33	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
34	OSF St. Francis Medical Center	Peoria	Illinois	United States	61637
35	Illinois CancerCare - Peru	Peru	Illinois	United States	61354
36	Illinois Valley Community Hospital	Peru	Illinois	United States	61354
37	Illinois CancerCare - Princeton	Princeton	Illinois	United States	61356
38	Perry Memorial Hospital	Princeton	Illinois	United States	61356
39	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana	United States	46107
40	Reid Hospital & Health Care Services	Richmond	Indiana	United States	47374
41		Bettendorf	Iowa	United States	52722
42	Medical Oncology and Hematology Associates - West Des Moines	Clive	Iowa	United States	50325
43	Mercy Cancer Center - West Lakes	Clive	Iowa	United States	50325
44	CCOP - Iowa Oncology Research Association	Des Moines	Iowa	United States	50309
45	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
46	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa	United States	50309
47	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa	United States	50314
48	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
49	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
50	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa	United States	51101
51	Mercy Medical Center - Sioux City	Sioux City	Iowa	United States	51102
52	St. Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
53	Methodist West Hospital	West Des Moines	Iowa	United States	50266-7700
54	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas	United States	66720
55	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas	United States	67801
56	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas	United States	67042
57	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas	United States	66701
58	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
59	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas	United States	67068
60	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
61	Cancer Center of Kansas, PA - Liberal	Liberal	Kansas	United States	67901
62	Cancer Center of Kansas, PA - Newton	Newton	Kansas	United States	67114
63	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas	United States	67357
64	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas	United States	67124
65	Cancer Center of Kansas, PA - Salina	Salina	Kansas	United States	67401
66	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas	United States	67152
67	Associates in Womens Health, PA - North Review	Wichita	Kansas	United States	67208
68	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas	United States	67208
69	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas	United States	67214
70	CCOP - Wichita	Wichita	Kansas	United States	67214
71	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
72	Wesley Medical Center	Wichita	Kansas	United States	67214
73	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas	United States	67156
74	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan	United States	48106-0995
75	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan	United States	48106
76	Battle Creek Health System Cancer Care Center	Battle Creek	Michigan	United States	49017
77	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan	United States	48123-2500
78	Green Bay Oncology, Limited - Escanaba	Escanaba	Michigan	United States	49431
79	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
80	Hurley Medical Center	Flint	Michigan	United States	48503
81	Butterworth Hospital at Spectrum Health	Grand Rapids	Michigan	United States	49503
82	CCOP - Grand Rapids	Grand Rapids	Michigan	United States	49503
83	Lacks Cancer Center at Saint Mary's Health Care	Grand Rapids	Michigan	United States	49503
84	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan	United States	48236
85	Dickinson County Healthcare System	Iron Mountain	Michigan	United States	49801
86	Foote Memorial Hospital	Jackson	Michigan	United States	49201
87	Sparrow Regional Cancer Center	Lansing	Michigan	United States	48912-1811
88	St. Mary Mercy Hospital	Livonia	Michigan	United States	48154
89	Mercy General Health Partners	Muskegon	Michigan	United States	49443
90	St. Joseph Mercy Oakland	Pontiac	Michigan	United States	48341-2985
91	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan	United States	48060
92	Spectrum Health Reed City Hospital	Reed City	Michigan	United States	49677
93	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan	United States	48601
94	Munson Medical Center	Traverse City	Michigan	United States	49684
95	St. John Macomb Hospital	Warren	Michigan	United States	48093
96	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
97	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota	United States	55433
98	Duluth Clinic Cancer Center - Duluth	Duluth	Minnesota	United States	55805-1983
99	CCOP - Duluth	Duluth	Minnesota	United States	55805
100	Miller - Dwan Medical Center	Duluth	Minnesota	United States	55805
101	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
102	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota	United States	55432
103	Hutchinson Area Health Care	Hutchinson	Minnesota	United States	55350
104	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota	United States	55109
105	Minnesota Oncology - Maplewood	Maplewood	Minnesota	United States	55109
106	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota	United States	55407
107	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota	United States	55415
108	Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota	United States	55422-2900
109	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
110	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
111	Park Nicollet Cancer Center	Saint Louis Park	Minnesota	United States	55416
112	Regions Hospital Cancer Care Center	Saint Paul	Minnesota	United States	55101
113	United Hospital	Saint Paul	Minnesota	United States	55102
114	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota	United States	55379
115	Lakeview Hospital	Stillwater	Minnesota	United States	55082
116	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
117	Willmar Cancer Center at Rice Memorial Hospital	Willmar	Minnesota	United States	56201
118	Minnesota Oncology - Woodbury	Woodbury	Minnesota	United States	55125
119	Central Care Cancer Center at Carrie J. Babb Cancer Center	Bolivar	Missouri	United States	65613
120	CCOP - Cancer Research for the Ozarks	Springfield	Missouri	United States	65802
121	St. John's Regional Health Center	Springfield	Missouri	United States	65804
122	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri	United States	65807
123	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
124	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana	United States	59102
125	Billings Clinic - Downtown	Billings	Montana	United States	59107-7000
126	Bozeman Deaconess Cancer Center	Bozeman	Montana	United States	59715
127	St. James Healthcare Cancer Care	Butte	Montana	United States	59701
128	Great Falls Clinic - Main Facility	Great Falls	Montana	United States	59405
129	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana	United States	59405
130	Northern Montana Hospital	Havre	Montana	United States	59501
131	St. Peter's Hospital	Helena	Montana	United States	59601
132	Glacier Oncology, PLLC	Kalispell	Montana	United States	59901
133	Kalispell Medical Oncology at KRMC	Kalispell	Montana	United States	59901
134	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
135	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana	United States	59807-7877
136	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana	United States	59807
137	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87131-5636
138	Rutherford Hospital	Rutherfordton	North Carolina	United States	28139
139	Dakota Cancer Institute at Dakota Clinic - South University	Fargo	North Dakota	United States	58103
140	Altru Cancer Center at Altru Hospital	Grand Forks	North Dakota	United States	58201
141	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
142	Riverside Methodist Hospital Cancer Care	Columbus	Ohio	United States	43214-3998
143	CCOP - Columbus	Columbus	Ohio	United States	43215
144	Grant Medical Center Cancer Care	Columbus	Ohio	United States	43215
145	Mount Carmel Health - West Hospital	Columbus	Ohio	United States	43222
146	Doctors Hospital at Ohio Health	Columbus	Ohio	United States	43228
147	Grandview Hospital	Dayton	Ohio	United States	45405
148	Good Samaritan Hospital	Dayton	Ohio	United States	45406
149	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio	United States	45409
150	Samaritan North Cancer Care Center	Dayton	Ohio	United States	45415
151	CCOP - Dayton	Dayton	Ohio	United States	45420
152	Grady Memorial Hospital	Delaware	Ohio	United States	43015
153	Blanchard Valley Medical Associates	Findlay	Ohio	United States	45840
154	Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
155	Wayne Hospital	Greenville	Ohio	United States	45331
156	Charles F. Kettering Memorial Hospital	Kettering	Ohio	United States	45429
157	Fairfield Medical Center	Lancaster	Ohio	United States	43130
158	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio	United States	45750
159	Knox Community Hospital	Mount Vernon	Ohio	United States	43050
160	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio	United States	43055
161	Community Hospital of Springfield and Clark County	Springfield	Ohio	United States	45505
162	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio	United States	45373-1300
163	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio	United States	43081
164	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio	United States	45385
165	Genesis - Good Samaritan Hospital	Zanesville	Ohio	United States	43701
166	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania	United States	17822-0001
167	Geisinger Hazleton Cancer Center	Hazleton	Pennsylvania	United States	18201
168	Geisinger Medical Group - Scenery Park	State College	Pennsylvania	United States	16801
169	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania	United States	18711
170	AnMed Cancer Center	Anderson	South Carolina	United States	29621
171	Bon Secours St. Francis Health System	Greenville	South Carolina	United States	29601
172	CCOP - Upstate Carolina	Spartanburg	South Carolina	United States	29303
173	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina	United States	29303
174	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
175	Midelfort Clinic - Luther	Eau Claire	Wisconsin	United States	54703-1510
176	Luther Midlelfort Hospital	Eau Claire	Wisconsin	United States	54703
177	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54301-3526
178	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin	United States	54303
179	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin	United States	54303
180	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54307-3508
181	Holy Family Memorial Medical Center Cancer Care Center	Manitowoc	Wisconsin	United States	54221-1450
182	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin	United States	54143
183	Green Bay Oncology, Limited - Oconto Falls	Oconto Falls	Wisconsin	United States	54154
184	St. Nicholas Hospital	Sheboygan	Wisconsin	United States	53081
185	Door County Cancer Center at Door County Memorial Hospital	Sturgeon Bay	Wisconsin	United States	54235-1495
186	Green Bay Oncology, Limited - Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235
187	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming	United States	82801

Sponsors and Collaborators

• Alliance for Clinical Trials in Oncology
• National Cancer Institute (NCI)

Investigators

• Study Chair: Steven R. Alberts, MD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alliance for Clinical Trials in Oncology
• ClinicalTrials.gov Identifier: NCT00938470
• Other Study ID Numbers: NCCTG-N0849; NCI-2011-01930; CDR0000646724
• First Posted: Jul 13, 2009
• Last Update Posted: Mar 29, 2018
• Last Verified: Mar 1, 2018

• Keywords provided by Alliance for Clinical Trials in Oncology: adenocarcinoma of the esophagus; adenocarcinoma of the gastroesophageal junction; stage IIIA gastric cancer; stage IIIB gastric cancer; stage IIIC gastric cancer; stage IIIA esophageal cancer; stage IIIB esophageal cancer; stage IIIC esophageal cancer
• Additional relevant MeSH terms: Adenocarcinoma; Stomach Neoplasms; Esophageal Neoplasms; Docetaxel; Fluorouracil; Capecitabine; Oxaliplatin

Study Results

Participant Flow

Recruitment Details	Seventy-three participants were enrolled between January 2010 and July 2012.
Pre-assignment Detail	Seven participants from arm I were enrolled in the early toxicity evaluation portion. Additional sixty-six participants were randomized to arm I or II on the phase II portion of the study. There were 11 cancellations (5 arm I, 6 arm II) and these participants were excluded in all analyses.

Arm/Group Title	Arm I (DOC, 5FU/O/RT, Surgery)	Arm II (5FU/O/RT, Surgery)
Arm/Group Description	Patients receive 60mg/m^2 docetaxel (D) IV over 1 hour and 85mg/m^2 oxaliplatin (O) IV over 2 hours on day 1. Patients also receive 625 mg/m^2/dose twice a day of capecitabine (C) PO BID on days 1-14. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. After completion of the second course, patients receive 180 mg/m^2 per day of fluorouracil (5FU) IV continuously on days 1-5 and 85 mg/m^2 oxaliplatin (O) IV over 2 hours on days 1, 15, and 29. Patients also undergo radiation therapy (RT) 5 days a week for 5.5 weeks in the absence of disease progression or unacceptable toxicity. Approximately 4-12 weeks after completion of radiation therapy, patients undergo surgery.	Patients receive 180 mg/m^2 per day of fluorouracil (5FU) IV continuously on days 1-5 and 85 mg/m^2 of oxaliplatin (O) IV over 2 hours on days 1, 15, and 29. Patients also undergo radiation therapy (RT) and then surgery.
Period Title: Overall Study
STARTED	34	28
COMPLETED	27	25
NOT COMPLETED	7	3

Baseline Characteristics

Arm/Group Title	Arm I (DOC, 5FU/O/RT, Surgery)	Arm II (5FU/O/RT, Surgery)	Total
Arm/Group Description	Patients receive 60mg/m^2 docetaxel (D) IV over 1 hour and 85mg/m^2 oxaliplatin (O) IV over 2 hours on day 1. Patients also receive 625 mg/m^2/dose twice a day of capecitabine (C) PO BID on days 1-14. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. After completion of the second course, patients receive 180 mg/m^2 per day of fluorouracil (5FU) IV continuously on days 1-5 and 85 mg/m^2 oxaliplatin (O) IV over 2 hours on days 1, 15, and 29. Patients also undergo radiation therapy (RT) 5 days a week for 5.5 weeks in the absence of disease progression or unacceptable toxicity. Approximately 4-12 weeks after completion of radiation therapy, patients undergo surgery.	Patients receive 180 mg/m^2 per day of fluorouracil (5FU) IV continuously on days 1-5 and 85 mg/m^2 of oxaliplatin (O) IV over 2 hours on days 1, 15, and 29. Patients also undergo radiation therapy (RT) and then surgery.	Total of all reporting groups
Overall Participants	28	27	55
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	62.5	65	63
Sex: Female, Male (Count of Participants)
Female	5 17.9%	4 14.8%	9 16.4%
Male	23 82.1%	23 85.2%	46 83.6%
Race/Ethnicity, Customized (Count of Participants)
White	28 100%	27 100%	55 100%
ECOG Performance Status 0-1 (Count of Participants)
Count of Participants [Participants]	28 100%	27 100%	55 100%
Tumor Stage (Count of Participants)
II	6 21.4%	9 33.3%	15 27.3%
III	22 78.6%	18 66.7%	40 72.7%
Site of Tumor (Count of Participants)
Esophagus	16 57.1%	11 40.7%	27 49.1%
Gastroesophageal Junction	12 42.9%	14 51.9%	26 47.3%
Gastric Cardia	0 0%	2 7.4%	2 3.6%
Measurable Disease (Count of Participants)
Yes	11 39.3%	11 40.7%	22 40%
No	17 60.7%	16 59.3%	33 60%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Pathologic Complete Response (PCR)
Description	Pathologic complete response was defined as no gross or microscopic tumor identified with the surgical specimen. All lymph nodes should be free of tumor to document a PCR. If no gross tumor is visible, section around the area of inflammation (nodularity) should be made every 2-3 cm and specimens examined.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Eligible randomized participants who initiated first cycle of protocol treatment.

Arm/Group Title	Arm I (DOC, 5FU/O/RT, Surgery)	Arm II (5FU/O/RT, Surgery)
Arm/Group Description	Patients receive 60mg/m^2 docetaxel (D) IV over 1 hour and 85mg/m^2 oxaliplatin (O) IV over 2 hours on day 1. Patients also receive 625 mg/m^2/dose twice a day of capecitabine (C) PO BID on days 1-14. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. After completion of the second course, patients receive 180 mg/m^2 per day of fluorouracil (5FU) IV continuously on days 1-5 and 85 mg/m^2 oxaliplatin (O) IV over 2 hours on days 1, 15, and 29. Patients also undergo radiation therapy (RT) 5 days a week for 5.5 weeks in the absence of disease progression or unacceptable toxicity. Approximately 4-12 weeks after completion of radiation therapy, patients undergo surgery.	Patients receive 180 mg/m^2 per day of fluorouracil (5FU) IV continuously on days 1-5 and 85 mg/m^2 of oxaliplatin (O) IV over 2 hours on days 1, 15, and 29. Patients also undergo radiation therapy (RT) and then surgery.
Measure Participants	28	27
Number (95% Confidence Interval) [percentage of participants]	28.6 102.1%	40.7 150.7%

2. Secondary Outcome

Title	Overall Survival
Description	Overall survival was defined as the time from randomization to the time of death from any cause. Overall survival was censored at the date of last follow-up visit for patients who are still alive or loss of follow-up.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Eligible randomized participants who initiated first cycle of protocol treatment.

Arm/Group Title	Arm I (DOC, 5FU/O/RT, Surgery)	Arm II (5FU/O/RT, Surgery)
Arm/Group Description	Patients receive 60mg/m^2 docetaxel (D) IV over 1 hour and 85mg/m^2 oxaliplatin (O) IV over 2 hours on day 1. Patients also receive 625 mg/m^2/dose twice a day of capecitabine (C) PO BID on days 1-14. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. After completion of the second course, patients receive 180 mg/m^2 per day of fluorouracil (5FU) IV continuously on days 1-5 and 85 mg/m^2 oxaliplatin (O) IV over 2 hours on days 1, 15, and 29. Patients also undergo radiation therapy (RT) 5 days a week for 5.5 weeks in the absence of disease progression or unacceptable toxicity. Approximately 4-12 weeks after completion of radiation therapy, patients undergo surgery.	Patients receive 180 mg/m^2 per day of fluorouracil (5FU) IV continuously on days 1-5 and 85 mg/m^2 of oxaliplatin (O) IV over 2 hours on days 1, 15, and 29. Patients also undergo radiation therapy (RT) and then surgery.
Measure Participants	28	27
Median (95% Confidence Interval) [months]	NA	18.8

3. Secondary Outcome

Title	Disease-free Survival
Description	Disease-free survival was defined as the time from randomization to the date of recurrent or death, whichever comes first.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Eligible randomized participants who initiated first cycle of protocol treatment.

Arm/Group Title	Arm I (DOC, 5FU/O/RT, Surgery)	Arm II (5FU/O/RT, Surgery)
Arm/Group Description	Patients receive 60mg/m^2 docetaxel (D) IV over 1 hour and 85mg/m^2 oxaliplatin (O) IV over 2 hours on day 1. Patients also receive 625 mg/m^2/dose twice a day of capecitabine (C) PO BID on days 1-14. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. After completion of the second course, patients receive 180 mg/m^2 per day of fluorouracil (5FU) IV continuously on days 1-5 and 85 mg/m^2 oxaliplatin (O) IV over 2 hours on days 1, 15, and 29. Patients also undergo radiation therapy (RT) 5 days a week for 5.5 weeks in the absence of disease progression or unacceptable toxicity. Approximately 4-12 weeks after completion of radiation therapy, patients undergo surgery.	Patients receive 180 mg/m^2 per day of fluorouracil (5FU) IV continuously on days 1-5 and 85 mg/m^2 of oxaliplatin (O) IV over 2 hours on days 1, 15, and 29. Patients also undergo radiation therapy (RT) and then surgery.
Measure Participants	28	27
Median (95% Confidence Interval) [months]	31.2	17.0

4. Secondary Outcome

Title	Number of Participants Who Experienced a Maximum Grade of 3 or Above Adverse Event
Description	Adverse events were assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Eligible randomized participants who initiated first cycle of protocol treatment.

Arm/Group Title	Arm I (DOC, 5FU/O/RT, Surgery)	Arm II (5FU/O/RT, Surgery)
Arm/Group Description	Patients receive 60mg/m^2 docetaxel (D) IV over 1 hour and 85mg/m^2 oxaliplatin (O) IV over 2 hours on day 1. Patients also receive 625 mg/m^2/dose twice a day of capecitabine (C) PO BID on days 1-14. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. After completion of the second course, patients receive 180 mg/m^2 per day of fluorouracil (5FU) IV continuously on days 1-5 and 85 mg/m^2 oxaliplatin (O) IV over 2 hours on days 1, 15, and 29. Patients also undergo radiation therapy (RT) 5 days a week for 5.5 weeks in the absence of disease progression or unacceptable toxicity. Approximately 4-12 weeks after completion of radiation therapy, patients undergo surgery.	Patients receive 180 mg/m^2 per day of fluorouracil (5FU) IV continuously on days 1-5 and 85 mg/m^2 of oxaliplatin (O) IV over 2 hours on days 1, 15, and 29. Patients also undergo radiation therapy (RT) and then surgery.
Measure Participants	28	27
Grade 3=Severe	10 35.7%	12 44.4%
Grade 4=Life threatening	10 35.7%	7 25.9%
Grade 5=Death	4 14.3%	4 14.8%

5. Secondary Outcome

Title	Percentage of Participants With Overall Clinical Tumor Response (CR or PR)
Description	Overall clinical tumor response rate was defined as the percentage of evaluable participants who achieved either complete response (CR) or partial response (PR) noted on the objective status from pre-surgical staging (for arm II) or either from pre-RT or pre-surgical staging (for arm I).> CR was defined as disappearance of all non-target lesion (TL) and normalization of tumor biomarker level, all lymph nodes (LN) must be non-pathological in size (<1 cm short axis); or disappearance of all TL and normalization of tumor biomarkers, any pathological LN (whether target or non-target) must have reduction in short axis to <1 cm; or >=30% decrease in the sum of the diameters of TL taking as reference the baseline sum of the diameters.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Eligible randomized participants who initiated first cycle of protocol treatment.

Arm/Group Title	Arm I (DOC, 5FU/O/RT, Surgery)	Arm II (5FU/O/RT, Surgery)
Arm/Group Description	Patients receive 60mg/m^2 docetaxel (D) IV over 1 hour and 85mg/m^2 oxaliplatin (O) IV over 2 hours on day 1. Patients also receive 625 mg/m^2/dose twice a day of capecitabine (C) PO BID on days 1-14. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. After completion of the second course, patients receive 180 mg/m^2 per day of fluorouracil (5FU) IV continuously on days 1-5 and 85 mg/m^2 oxaliplatin (O) IV over 2 hours on days 1, 15, and 29. Patients also undergo radiation therapy (RT) 5 days a week for 5.5 weeks in the absence of disease progression or unacceptable toxicity. Approximately 4-12 weeks after completion of radiation therapy, patients undergo surgery.	Patients receive 180 mg/m^2 per day of fluorouracil (5FU) IV continuously on days 1-5 and 85 mg/m^2 of oxaliplatin (O) IV over 2 hours on days 1, 15, and 29. Patients also undergo radiation therapy (RT) and then surgery.
Measure Participants	28	27
Number (95% Confidence Interval) [percentage of participants]	32.1 114.6%	33.3 123.3%

Adverse Events

Time Frame	2 years
Adverse Event Reporting Description	Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Arm/Group Title	Arm I (DOC, 5FU/O/RT, Surgery)		Arm II (5FU/O/RT, Surgery)
Arm/Group Description	Patients receive 60mg/m^2 docetaxel (D) IV over 1 hour and 85mg/m^2 oxaliplatin (O) IV over 2 hours on day 1. Patients also receive 625 mg/m^2/dose twice a day of capecitabine (C) PO BID on days 1-14. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. After completion of the second course, patients receive 180 mg/m^2 per day of fluorouracil (5FU) IV continuously on days 1-5 and 85 mg/m^2 oxaliplatin (O) IV over 2 hours on days 1, 15, and 29. Patients also undergo radiation therapy (RT) 5 days a week for 5.5 weeks in the absence of disease progression or unacceptable toxicity. Approximately 4-12 weeks after completion of radiation therapy, patients undergo surgery.		Patients receive 180 mg/m^2 per day of fluorouracil (5FU) IV continuously on days 1-5 and 85 mg/m^2 of oxaliplatin (O) IV over 2 hours on days 1, 15, and 29. Patients also undergo radiation therapy (RT) and then surgery.
All Cause Mortality
	Arm I (DOC, 5FU/O/RT, Surgery)		Arm II (5FU/O/RT, Surgery)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I (DOC, 5FU/O/RT, Surgery)		Arm II (5FU/O/RT, Surgery)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/34 (20.6%)		7/28 (25%)
Blood and lymphatic system disorders
Disseminated intravascular coagulation	1/34 (2.9%)	1	0/28 (0%)	0
Cardiac disorders
Cardiac arrest	1/34 (2.9%)	1	0/28 (0%)	0
Gastrointestinal disorders
Colitis	1/34 (2.9%)	1	0/28 (0%)	0
Dysphagia	0/34 (0%)	0	1/28 (3.6%)	1
Esophageal fistula	0/34 (0%)	0	1/28 (3.6%)	1
Esophageal pain	0/34 (0%)	0	1/28 (3.6%)	1
Retroperitoneal hemorrhage	1/34 (2.9%)	1	0/28 (0%)	0
Upper gastrointestinal hemorrhage	1/34 (2.9%)	1	0/28 (0%)	0
General disorders
Death NOS	0/34 (0%)	0	1/28 (3.6%)	1
Infections and infestations
Sepsis	1/34 (2.9%)	1	2/28 (7.1%)	2
Injury, poisoning and procedural complications
Esophageal anastomotic leak	0/34 (0%)	0	1/28 (3.6%)	1
Investigations
Lymphocyte count decreased	2/34 (5.9%)	2	0/28 (0%)	0
Neutrophil count decreased	1/34 (2.9%)	1	0/28 (0%)	0
Platelet count decreased	1/34 (2.9%)	1	0/28 (0%)	0
White blood cell decreased	2/34 (5.9%)	2	0/28 (0%)	0
Metabolism and nutrition disorders
Anorexia	0/34 (0%)	0	1/28 (3.6%)	1
Hyperglycemia	1/34 (2.9%)	1	0/28 (0%)	0
Respiratory, thoracic and mediastinal disorders
Aspiration	0/34 (0%)	0	1/28 (3.6%)	1
Bronchopulmonary hemorrhage	1/34 (2.9%)	1	0/28 (0%)	0
Pneumothorax	0/34 (0%)	0	1/28 (3.6%)	1
Respiratory failure	2/34 (5.9%)	2	2/28 (7.1%)	2
Other (Not Including Serious) Adverse Events
	Arm I (DOC, 5FU/O/RT, Surgery)		Arm II (5FU/O/RT, Surgery)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	34/34 (100%)		28/28 (100%)
Blood and lymphatic system disorders
Anemia	7/34 (20.6%)	10	8/28 (28.6%)	11
Febrile neutropenia	1/34 (2.9%)	1	0/28 (0%)	0
Cardiac disorders
Asystole	0/34 (0%)	0	1/28 (3.6%)	1
Atrial fibrillation	4/34 (11.8%)	5	1/28 (3.6%)	1
Atrial flutter	1/34 (2.9%)	1	1/28 (3.6%)	1
Cardiac arrest	0/34 (0%)	0	2/28 (7.1%)	2
Heart failure	0/34 (0%)	0	1/28 (3.6%)	1
Myocardial infarction	1/34 (2.9%)	1	0/28 (0%)	0
Pericardial effusion	1/34 (2.9%)	1	0/28 (0%)	0
Pericardial tamponade	1/34 (2.9%)	1	0/28 (0%)	0
Sinus bradycardia	0/34 (0%)	0	2/28 (7.1%)	3
Supraventricular tachycardia	1/34 (2.9%)	1	0/28 (0%)	0
Ventricular fibrillation	0/34 (0%)	0	1/28 (3.6%)	1
Ventricular tachycardia	0/34 (0%)	0	1/28 (3.6%)	1
Gastrointestinal disorders
Abdominal pain	5/34 (14.7%)	7	1/28 (3.6%)	1
Colonic obstruction	1/34 (2.9%)	1	0/28 (0%)	0
Colonic perforation	0/34 (0%)	0	1/28 (3.6%)	1
Constipation	1/34 (2.9%)	1	1/28 (3.6%)	1
Diarrhea	21/34 (61.8%)	41	15/28 (53.6%)	22
Dry mouth	0/34 (0%)	0	1/28 (3.6%)	1
Duodenal fistula	0/34 (0%)	0	1/28 (3.6%)	1
Dyspepsia	2/34 (5.9%)	2	1/28 (3.6%)	1
Dysphagia	26/34 (76.5%)	68	22/28 (78.6%)	41
Esophageal fistula	1/34 (2.9%)	1	0/28 (0%)	0
Esophageal pain	2/34 (5.9%)	2	1/28 (3.6%)	1
Esophageal perforation	0/34 (0%)	0	1/28 (3.6%)	1
Esophageal stenosis	0/34 (0%)	0	1/28 (3.6%)	2
Esophagitis	3/34 (8.8%)	3	6/28 (21.4%)	6
Flatulence	1/34 (2.9%)	1	1/28 (3.6%)	1
Gastric fistula	1/34 (2.9%)	1	0/28 (0%)	0
Gastritis	1/34 (2.9%)	1	2/28 (7.1%)	2
Gastroesophageal reflux disease	1/34 (2.9%)	2	1/28 (3.6%)	1
Gastrointestinal disorders - Other, specify	1/34 (2.9%)	3	2/28 (7.1%)	2
Gastroparesis	0/34 (0%)	0	1/28 (3.6%)	2
Ileus	0/34 (0%)	0	1/28 (3.6%)	1
Mucositis oral	1/34 (2.9%)	1	1/28 (3.6%)	1
Nausea	30/34 (88.2%)	83	24/28 (85.7%)	44
Oral dysesthesia	0/34 (0%)	0	1/28 (3.6%)	1
Small intestinal obstruction	0/34 (0%)	0	1/28 (3.6%)	1
Upper gastrointestinal hemorrhage	1/34 (2.9%)	1	0/28 (0%)	0
Vomiting	21/34 (61.8%)	35	18/28 (64.3%)	32
General disorders
Edema limbs	2/34 (5.9%)	2	1/28 (3.6%)	1
Edema trunk	1/34 (2.9%)	1	0/28 (0%)	0
Fatigue	15/34 (44.1%)	28	11/28 (39.3%)	14
Fever	2/34 (5.9%)	2	2/28 (7.1%)	2
Hypothermia	1/34 (2.9%)	1	0/28 (0%)	0
Infusion related reaction	1/34 (2.9%)	1	0/28 (0%)	0
Multi-organ failure	0/34 (0%)	0	1/28 (3.6%)	1
Non-cardiac chest pain	1/34 (2.9%)	1	0/28 (0%)	0
Pain	0/34 (0%)	0	2/28 (7.1%)	2
Infections and infestations
Abdominal infection	0/34 (0%)	0	1/28 (3.6%)	1
Bone infection	1/34 (2.9%)	2	0/28 (0%)	0
Infections and infestations - Other, specify	1/34 (2.9%)	5	2/28 (7.1%)	2
Lung infection	2/34 (5.9%)	3	0/28 (0%)	0
Mucosal infection	1/34 (2.9%)	1	0/28 (0%)	0
Sepsis	3/34 (8.8%)	3	1/28 (3.6%)	1
Skin infection	0/34 (0%)	0	1/28 (3.6%)	1
Tooth infection	1/34 (2.9%)	1	0/28 (0%)	0
Upper respiratory infection	1/34 (2.9%)	1	1/28 (3.6%)	1
Injury, poisoning and procedural complications
Esophageal anastomotic leak	2/34 (5.9%)	2	1/28 (3.6%)	1
Gastric anastomotic leak	1/34 (2.9%)	1	0/28 (0%)	0
Gastrointestinal anastomotic leak	0/34 (0%)	0	1/28 (3.6%)	1
Injury, poisoning and procedural complications - Other, specify	1/34 (2.9%)	5	0/28 (0%)	0
Intraoperative hemorrhage	0/34 (0%)	0	1/28 (3.6%)	1
Wound complication	0/34 (0%)	0	1/28 (3.6%)	1
Wound dehiscence	2/34 (5.9%)	2	0/28 (0%)	0
Investigations
Activated partial thromboplastin time prolonged	0/34 (0%)	0	1/28 (3.6%)	2
Alanine aminotransferase increased	1/34 (2.9%)	1	2/28 (7.1%)	2
Alkaline phosphatase increased	1/34 (2.9%)	1	2/28 (7.1%)	2
Aspartate aminotransferase increased	0/34 (0%)	0	2/28 (7.1%)	2
Blood bilirubin increased	4/34 (11.8%)	5	1/28 (3.6%)	1
Creatinine increased	1/34 (2.9%)	1	3/28 (10.7%)	4
INR increased	0/34 (0%)	0	1/28 (3.6%)	1
Lymphocyte count decreased	4/34 (11.8%)	5	9/28 (32.1%)	14
Neutrophil count decreased	28/34 (82.4%)	47	5/28 (17.9%)	5
Platelet count decreased	22/34 (64.7%)	66	22/28 (78.6%)	43
Weight loss	8/34 (23.5%)	20	8/28 (28.6%)	12
White blood cell decreased	28/34 (82.4%)	74	13/28 (46.4%)	20
Metabolism and nutrition disorders
Anorexia	8/34 (23.5%)	10	11/28 (39.3%)	12
Dehydration	7/34 (20.6%)	9	5/28 (17.9%)	5
Hyperglycemia	4/34 (11.8%)	6	5/28 (17.9%)	6
Hypermagnesemia	0/34 (0%)	0	1/28 (3.6%)	1
Hypernatremia	1/34 (2.9%)	1	1/28 (3.6%)	1
Hypoalbuminemia	6/34 (17.6%)	8	3/28 (10.7%)	4
Hypocalcemia	1/34 (2.9%)	1	3/28 (10.7%)	4
Hypoglycemia	1/34 (2.9%)	1	0/28 (0%)	0
Hypokalemia	3/34 (8.8%)	4	3/28 (10.7%)	3
Hypophosphatemia	3/34 (8.8%)	3	1/28 (3.6%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/34 (2.9%)	1	0/28 (0%)	0
Bone pain	0/34 (0%)	0	1/28 (3.6%)	1
Chest wall pain	1/34 (2.9%)	3	1/28 (3.6%)	2
Flank pain	1/34 (2.9%)	1	0/28 (0%)	0
Generalized muscle weakness	4/34 (11.8%)	8	0/28 (0%)	0
Muscle weakness lower limb	0/34 (0%)	0	1/28 (3.6%)	1
Musculoskeletal and connective tissue disorder - Other, specify	1/34 (2.9%)	2	0/28 (0%)	0
Myalgia	0/34 (0%)	0	2/28 (7.1%)	2
Pain in extremity	1/34 (2.9%)	1	1/28 (3.6%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	0/34 (0%)	0	1/28 (3.6%)	1
Nervous system disorders
Depressed level of consciousness	1/34 (2.9%)	1	0/28 (0%)	0
Dizziness	0/34 (0%)	0	1/28 (3.6%)	1
Dysgeusia	0/34 (0%)	0	1/28 (3.6%)	1
Headache	0/34 (0%)	0	1/28 (3.6%)	1
Peripheral motor neuropathy	2/34 (5.9%)	4	3/28 (10.7%)	5
Peripheral sensory neuropathy	23/34 (67.6%)	59	18/28 (64.3%)	24
Seizure	0/34 (0%)	0	1/28 (3.6%)	1
Psychiatric disorders
Agitation	2/34 (5.9%)	2	0/28 (0%)	0
Anxiety	1/34 (2.9%)	2	0/28 (0%)	0
Delirium	1/34 (2.9%)	1	0/28 (0%)	0
Depression	2/34 (5.9%)	5	0/28 (0%)	0
Psychiatric disorders - Other, specify	1/34 (2.9%)	1	0/28 (0%)	0
Renal and urinary disorders
Acute kidney injury	1/34 (2.9%)	1	2/28 (7.1%)	2
Renal and urinary disorders - Other, specify	0/34 (0%)	0	1/28 (3.6%)	1
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome	1/34 (2.9%)	1	0/28 (0%)	0
Aspiration	0/34 (0%)	0	1/28 (3.6%)	1
Bronchial fistula	1/34 (2.9%)	1	0/28 (0%)	0
Chylothorax	3/34 (8.8%)	3	0/28 (0%)	0
Cough	2/34 (5.9%)	2	0/28 (0%)	0
Dyspnea	14/34 (41.2%)	44	13/28 (46.4%)	19
Hypoxia	2/34 (5.9%)	2	2/28 (7.1%)	2
Laryngeal inflammation	1/34 (2.9%)	1	0/28 (0%)	0
Pleural effusion	2/34 (5.9%)	2	3/28 (10.7%)	3
Pulmonary edema	1/34 (2.9%)	1	1/28 (3.6%)	1
Respiratory failure	3/34 (8.8%)	3	4/28 (14.3%)	4
Respiratory, thoracic and mediastinal disorders - Other, specify	2/34 (5.9%)	3	0/28 (0%)	0
Sore throat	1/34 (2.9%)	1	0/28 (0%)	0
Skin and subcutaneous tissue disorders
Alopecia	8/34 (23.5%)	13	0/28 (0%)	0
Hyperhidrosis	0/34 (0%)	0	1/28 (3.6%)	1
Palmar-plantar erythrodysesthesia syndrome	1/34 (2.9%)	2	0/28 (0%)	0
Rash acneiform	0/34 (0%)	0	1/28 (3.6%)	1
Rash maculo-papular	2/34 (5.9%)	2	0/28 (0%)	0
Skin ulceration	0/34 (0%)	0	1/28 (3.6%)	1
Surgical and medical procedures
Surgical and medical procedures - Other, specify	3/34 (8.8%)	9	0/28 (0%)	0
Vascular disorders
Hypotension	2/34 (5.9%)	2	1/28 (3.6%)	1
Thromboembolic event	2/34 (5.9%)	2	1/28 (3.6%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.