Cetuximab, Cisplatin, Fluorouracil, and Radiation Therapy in Treating Patients With Anal Cancer

• Sponsor: ECOG-ACRIN Cancer Research Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00316888
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 63
• Locations: 125
• Arms: 2
• Actual Duration (Months): 175.5
• Patients Per Site: 0.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some find tumor cells and kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as cisplatin and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Cetuximab may help cisplatin and fluorouracil work better by making tumor cells more sensitive to the drugs. It may also make tumor cells more sensitive to radiation therapy. Giving cetuximab together with chemotherapy and radiation therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving cetuximab together with cisplatin, fluorouracil, and radiation therapy works in treating immunocompetent patients with stage I (closed to accrual as of 11/3/2008), stage II, (some stage II closed to accrual as of 11/3/2008) or stage III anal cancer.

Condition or Disease	Intervention/Treatment	Phase
Anal Cancer	Biological: cetuximab; Drug: cisplatin; Drug: fluorouracil; Radiation: radiotherapy	Phase 2

Detailed Description

OBJECTIVES:

Primary Objective:

• Determine whether the addition of cetuximab to combined modality therapy (CMT) comprising cisplatin, fluorouracil, and radiotherapy reduces the local failure rate by ≥ 50% at 3 years (compared with historical data) in immunocompetent patients with stage I-III invasive anal carcinoma.

Secondary Objectives:

• Determine objective response rate (complete and partial), progression-free survival, colostomy-free survival, and overall survival.

• Determine the overall toxicity of concurrent cisplatin, fluorouracil, and radiation therapy combined with cetuximab.

Exploratory Objectives:

• Evaluate the effect of cetuximab and CMT on anogenital herpes papilloma virus (HPV) infection and anal cytology.

• Evaluate whether moderate to strong expression of epidermal growth factor receptor, Phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), and P-Akt (as determined by immunohistochemistry) is associated with an increased risk of local failure.

OUTLINE: This is a multicenter study with two sequential arms. Arm I was closed to accrual as of 11/3/2008, and arm II opened to accrual on 8/18/2009. Patients are assigned to 1 of the 2 treatment arms.

• Arm I (closed to accrual as of 11/3/2008): Patients receive cisplatin intravenously (IV) over 60 minutes on days 1, 29, 57, and 85 and fluorouracil IV continuously over 96 hours on days 1-4, 29-32, 57-60, and 85-88. Patients also receive cetuximab IV over 120 minutes on day 50 and then IV over 60 minutes on days 57, 64, 71, 78, 85, 92, and 99 and undergo radiotherapy once daily 5 days a week for 5 weeks, beginning on day 57.

• Arm II (open to accrual on 8/18/2009): Patients receive cetuximab IV over 120 minutes on day 1 and then IV over 60 minutes on days 8, 15, 22, 29, 36, 43, and 50. Patients also receive cisplatin IV over 60 minutes on days 8 and 36, fluorouracil IV continuously over 96 hours on days 8-11 and 36-39, and undergo radiotherapy once daily 5 days a week for 5 weeks beginning on day 8.

After completion of study treatment, patients are followed periodically for up to 10 years.

PROJECTED ACCRUAL: A total of 62 patients will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 63 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Cetuximab Plus Cisplatin, 5- Fluorouracil and Radiation in Immunocompetent Patients With Anal Carcinoma
• Actual Study Start Date: Jan 1, 2007
• Actual Primary Completion Date: Nov 1, 2015
• Actual Study Completion Date: Aug 17, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (closed to accrual as of 11/3/2008) Patients receive cisplatin IV over 60 minutes on days 1, 29, 57, and 85 and fluorouracil IV continuously over 96 hours on days 1-4, 29-32, 57-60, and 85-88. Patients also receive cetuximab IV over 120 minutes on day 50 and then IV over 60 minutes on days 57, 64, 71, 78, 85, 92, and 99 and undergo radiotherapy once daily 5 days a week for 5 weeks, beginning on day 57. Treatment continues in the absence of disease progression or unacceptable toxicity.	Biological: cetuximab; Given IV; Other Names: Erbitux ; Drug: cisplatin; Given IV; Other Names: Cis-diaminedichloroplatinum Cis-diaminedichloroplatinum (II) Platinol Platinol-AQ cis-platinum diaminedichloroplatinum DDP ; Drug: fluorouracil; Given IV; Other Names: 5-Fluorouracil 5-FU Adrucil Efudex ; Radiation: radiotherapy; Given once daily 5 days a week for 5 weeks; Other Names: radiation therapy
Experimental: Arm II (open to accrual on 8/18/2009) Patients receive cetuximab IV over 120 minutes on day 1 and then IV over 60 minutes on days 8, 15, 22, 29, 36, 43, and 50. Patients also receive cisplatin IV over 60 minutes on days 1 and 36, fluorouracil IV continuously over 96 hours on days 8-11 and 36-39, and undergo radiotherapy once daily 5 days a week for 5 weeks beginning on day 8. Treatment continues in the absence of disease progression or unacceptable toxicity.	Biological: cetuximab; Given IV; Other Names: Erbitux ; Drug: cisplatin; Given IV; Other Names: Cis-diaminedichloroplatinum Cis-diaminedichloroplatinum (II) Platinol Platinol-AQ cis-platinum diaminedichloroplatinum DDP ; Drug: fluorouracil; Given IV; Other Names: 5-Fluorouracil 5-FU Adrucil Efudex ; Radiation: radiotherapy; Given once daily 5 days a week for 5 weeks; Other Names: radiation therapy

Outcome Measures

Primary Outcome Measures

1. Local Failure Rate at 3 Years [assessed every 3 months for patients within 2 years of registration, then every 6 months for patients in year 3]

   Local failure was defined as progression/relapse of disease in the anal canal and/or regional organs and/or regional lymph nodes after completion of protocol therapy, or progression during protocol therapy. Lost to follow-up and death (regardless of cause of death) prior to 3 years were also considered as local failures. For the calculation of local failure rate at 3 years, patients were classified into two groups (ie, coded as binary variable): failure (patients with local failure events prior to 3 years) vs. no failure (patients who still alive and had no local failure at 3 years). The binomial proportion and its exact two-sided 80% confidence interval (CI) were used to estimate it.

Secondary Outcome Measures

1. 3-year Overall Survival Rate [assessed every 3 months for patients within 2 years of registration, then every 6 months for patients in year 3]

   Overall survival (OS) is defined as time from registration to death from any cause. Patients alive are censored at the last contact date. Kaplan-Meier method was used to estimate the 3-year OS rate.

2. 3-year Progression-free Survival Rate [assessed every 3 months for patients within 2 years of registration, then every 6 months for patients in year 3]

   Progression-free survival (PFS) was defined as time from registration to disease progression, relapse or death (whichever occurred first), censoring cases without PFS events at the date of last disease assessment documenting the patient was free of progression/relapse. Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Kaplan-Meier method was used to estimate the 3-year PFS rate.

3. Objective Response Rate [Tumor assessments were made at baseline, within 4 weeks of the completion of protocol treatment, then every 6 months if patient was 1-4 years from registration, yearly if patient was 5-10 years from registration until progression/relapse using the RECIST]

   Objective response rate is defined as number of patients with complete response (CR) or partial response (PR) divided by all eligible and treated patients. Responses are evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline. CR is defined as disappearance of all target and non-target lesions. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameters), and/or persistence of one or more non-target lesion(s).

4. 3-year Colostomy-free Survival Rate [assessed every 3 months for patients within 2 years of registration, then every 6 months for patients in year 3]

   Colostomy-free survival was defined as time from registration until time of colostomy or death without colostomy, censoring cases without colostomy at the data of last disease assessment documenting the patient was free of colostomy. Kaplan-Meier method was used to estimate the 3-year colostomy-free survival rate.

Eligibility Criteria

Criteria

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

INCLUSION CRITERIA:

• Histologically confirmed anal canal or perianal (anal margin) squamous cell carcinoma

• Stage I-IIIB (closed to accrual as of 11/3/2008)

• Stage II (T3, N0 only), IIIA, or IIIB

• Tumors of nonkeratinizing histology, such as basaloid, transitional cell, or cloacogenic histology, allowed

• No well-differentiated stage I anal margin cancer

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

• Hemoglobin ≥ 10 g/dL

• Platelet count ≥ 100,000/mm^3

• Absolute neutrophil count > 1,500/mm^3

• Creatinine ≤ 1.5 times upper limit of normal (ULN) OR creatinine clearance > 60 mL/min

• Bilirubin ≤ 2 times ULN

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 times ULN

• Negative pregnancy test

• Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment

• No other malignancies except nonmelanomatous skin cancer

• Prior malignancies must be in remission for ≥ 5 years

• Patients with a known risk factor for human immunodeficiency virus (HIV) infection must undergo HIV testing within 90 days before study entry AND must be HIV negative by antibody detection, culture, or quantitative assay of plasma HIV ribonucleic acid (RNA)

EXCLUSION CRITERIA:

• Presence of the following conditions within the past 6 months:

• Active infection

• Uncontrolled diabetes

• New York Heart Association class II-IV congestive heart failure

• Cerebrovascular accident

• Transient ischemic attack

• Uncontrolled hypertension

• Unstable angina

• Myocardial infarction

• History of rheumatic disorders, irritable bowel syndrome, or inflammatory bowel disease

• Known HIV positivity

• Known risk factors for HIV infection

• Prior radiotherapy or chemotherapy for this malignancy

• Prior pelvic radiotherapy

• Prior potentially curative surgery (i.e., abdominal or peritoneal resection) for anal cancer

• Pregnant or nursing

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford Cancer Center	Stanford	California	United States	94305-5824
2	Poudre Valley Hospital	Fort Collins	Colorado	United States	80524
3	Front Range Cancer Specialists	Fort Collins	Colorado	United States	80528
4	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois	United States	60611-3013
5	Hematology and Oncology Associates	Chicago	Illinois	United States	60611
6	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois	United States	62526
7	Kellogg Cancer Care Center	Highland Park	Illinois	United States	60035
8	Provena St. Mary's Regional Cancer Center - Kankakee	Kankakee	Illinois	United States	60901
9	North Shore Oncology and Hematology Associates, Limited - Libertyville	Libertyville	Illinois	United States	60048
10	Cancer Care and Hematology Specialists of Chicagoland - Niles	Niles	Illinois	United States	60714
11	Swedish-American Regional Cancer Center	Rockford	Illinois	United States	61104-2315
12	Hematology Oncology Associates - Skokie	Skokie	Illinois	United States	60076
13	CCOP - Carle Cancer Center	Urbana	Illinois	United States	61801
14	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana	United States	46202-5289
15	William N. Wishard Memorial Hospital	Indianapolis	Indiana	United States	46202
16	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa	United States	52403
17	Mercy Regional Cancer Center at Mercy Medical Center	Cedar Rapids	Iowa	United States	52403
18	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa	United States	51101
19	Mercy Medical Center - Sioux City	Sioux City	Iowa	United States	51102
20	St. Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
21	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas	United States	66720
22	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas	United States	67801
23	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas	United States	67042
24	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas	United States	66701
25	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
26	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas	United States	67068
27	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
28	Cancer Center of Kansas, PA - Liberal	Liberal	Kansas	United States	67901
29	Cancer Center of Kansas, PA - Newton	Newton	Kansas	United States	67114
30	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas	United States	67357
31	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas	United States	67124
32	Cancer Center of Kansas, PA - Salina	Salina	Kansas	United States	67401
33	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas	United States	67152
34	Associates in Womens Health, PA - North Review	Wichita	Kansas	United States	67208
35	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas	United States	67208
36	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas	United States	67214
37	CCOP - Wichita	Wichita	Kansas	United States	67214
38	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
39	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas	United States	67156
40	Mary Bird Perkins Cancer Center - Baton Rouge	Baton Rouge	Louisiana	United States	70809
41	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana	United States	70112
42	Medical Center of Louisiana - New Orleans	New Orleans	Louisiana	United States	70112
43	Greater Baltimore Medical Center Cancer Center	Baltimore	Maryland	United States	21204
44	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan	United States	49221
45	Borgess Medical Center	Kalamazoo	Michigan	United States	49001
46	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007-3731
47	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
48	Community Cancer Center of Monroe	Monroe	Michigan	United States	48162
49	Mercy Memorial Hospital - Monroe	Monroe	Michigan	United States	48162
50	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
51	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota	United States	55433
52	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
53	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota	United States	55432
54	Hutchinson Area Health Care	Hutchinson	Minnesota	United States	55350
55	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota	United States	55109
56	Minnesota Oncology - Maplewood	Maplewood	Minnesota	United States	55109
57	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota	United States	55407
58	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota	United States	55415
59	Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota	United States	55422-2900
60	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
61	Park Nicollet Cancer Center	Saint Louis Park	Minnesota	United States	55416
62	Regions Hospital Cancer Care Center	Saint Paul	Minnesota	United States	55101
63	United Hospital	Saint Paul	Minnesota	United States	55102
64	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota	United States	55379
65	Lakeview Hospital	Stillwater	Minnesota	United States	55082
66	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
67	Willmar Cancer Center at Rice Memorial Hospital	Willmar	Minnesota	United States	56201
68	Minnesota Oncology - Woodbury	Woodbury	Minnesota	United States	55125
69	Cancer Resource Center - Lincoln	Lincoln	Nebraska	United States	68510
70	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska	United States	68106
71	Immanuel Medical Center	Omaha	Nebraska	United States	68122
72	Alegant Health Cancer Center at Bergan Mercy Medical Center	Omaha	Nebraska	United States	68124
73	Lakeside Hospital	Omaha	Nebraska	United States	68130
74	Creighton University Medical Center	Omaha	Nebraska	United States	68131-2197
75	Carol G. Simon Cancer Center at Morristown Memorial Hospital	Morristown	New Jersey	United States	07962
76	Overlook Hospital	Summit	New Jersey	United States	07902
77	Albert Einstein Cancer Center at Albert Einstein College of Medicine	Bronx	New York	United States	10461
78	NYU Cancer Institute at New York University Medical Center	New York	New York	United States	10016
79	Wood County Oncology Center	Bowling Green	Ohio	United States	43402
80	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
81	Riverside Methodist Hospital Cancer Care	Columbus	Ohio	United States	43214-3998
82	CCOP - Columbus	Columbus	Ohio	United States	43215
83	Grant Medical Center Cancer Care	Columbus	Ohio	United States	43215
84	Mount Carmel Health - West Hospital	Columbus	Ohio	United States	43222
85	Doctors Hospital at Ohio Health	Columbus	Ohio	United States	43228
86	Grady Memorial Hospital	Delaware	Ohio	United States	43015
87	Community Cancer Center	Elyria	Ohio	United States	44035
88	Hematology Oncology Center	Elyria	Ohio	United States	44035
89	Fairfield Medical Center	Lancaster	Ohio	United States	43130
90	Lima Memorial Hospital	Lima	Ohio	United States	45804
91	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio	United States	45750
92	Northwest Ohio Oncology Center	Maumee	Ohio	United States	43537-1839
93	Knox Community Hospital	Mount Vernon	Ohio	United States	43050
94	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio	United States	43055
95	St. Charles Mercy Hospital	Oregon	Ohio	United States	43616
96	Toledo Clinic - Oregon	Oregon	Ohio	United States	43616
97	Southern Ohio Medical Center Cancer Center	Portsmouth	Ohio	United States	45662
98	Community Hospital of Springfield and Clark County	Springfield	Ohio	United States	45505
99	Flower Hospital Cancer Center	Sylvania	Ohio	United States	43560
100	Mercy Hospital of Tiffin	Tiffin	Ohio	United States	44883
101	Toledo Hospital	Toledo	Ohio	United States	43606
102	St. Vincent Mercy Medical Center	Toledo	Ohio	United States	43608
103	Medical University of Ohio Cancer Center	Toledo	Ohio	United States	43614
104	CCOP - Toledo Community Hospital	Toledo	Ohio	United States	43617
105	St. Anne Mercy Hospital	Toledo	Ohio	United States	43623
106	Toledo Clinic, Incorporated - Main Clinic	Toledo	Ohio	United States	43623
107	Fulton County Health Center	Wauseon	Ohio	United States	43567
108	Genesis - Good Samaritan Hospital	Zanesville	Ohio	United States	43701
109	Joan Karnell Cancer Center at Pennsylvania Hospital	Philadelphia	Pennsylvania	United States	19107
110	Fox Chase Cancer Center - Philadelphia	Philadelphia	Pennsylvania	United States	19111-2497
111	Hematology and Oncology Associates of Northeastern Pennsylvania	Scranton	Pennsylvania	United States	18510
112	University of Virginia Cancer Center	Charlottesville	Virginia	United States	22908
113	Fredericksburg Oncology, Incorporated	Fredericksburg	Virginia	United States	22401
114	Marshfield Clinic - Chippewa Center	Chippewa Falls	Wisconsin	United States	54729
115	Marshfield Clinic Cancer Care at Regional Cancer Center	Eau Claire	Wisconsin	United States	54701
116	UW Cancer Center Johnson Creek	Johnson Creek	Wisconsin	United States	53038
117	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Madison	Wisconsin	United States	53792-6164
118	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin	United States	54449
119	Marshfield Clinic - Lakeland Center	Minocqua	Wisconsin	United States	54548
120	Ministry Medical Group at Saint Mary's Hospital	Rhinelander	Wisconsin	United States	54501
121	Marshfield Clinic - Indianhead Center	Rice Lake	Wisconsin	United States	54868
122	Marshfield Clinic at Saint Michael's Hospital	Stevens Point	Wisconsin	United States	54481
123	Marshfield Clinic - Wausau Center	Wausau	Wisconsin	United States	54401
124	Marshfield Clinic - Weston Center	Weston	Wisconsin	United States	54476
125	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin	United States	54494

Sponsors and Collaborators

• ECOG-ACRIN Cancer Research Group
• National Cancer Institute (NCI)

Investigators

• Study Chair: Madhur K. Garg, MD, Montefiore Medical Center
• Study Chair: Joseph A. Sparano, MD, Montefiore Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

• Garg M, Lee JY, Kachnic LA, et al.: Phase II trials of cetuximab (CX) plus cisplatin (CDDP), 5-fluorouracil (5-FU) and radiation (RT) in immunocompetent (ECOG 3205) and HIV-positive (AMC045) patients with squamous cell carcinoma of the anal canal (SCAC): safety and preliminary efficacy results. [Abstract] J Clin Oncol 30 (Suppl 15): A-4030, 2012.

• Responsible Party: ECOG-ACRIN Cancer Research Group
• ClinicalTrials.gov Identifier: NCT00316888
• Other Study ID Numbers: E3205; E3205; U10CA023318; CDR0000470269
• First Posted: Apr 21, 2006
• Last Update Posted: Jun 29, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by ECOG-ACRIN Cancer Research Group: squamous cell carcinoma of the anus; stage I anal cancer; stage II anal cancer; stage IIIA anal cancer; stage IIIB anal cancer; basaloid carcinoma of the anus; cloacogenic carcinoma of the anus
• Additional relevant MeSH terms: Anus Neoplasms; Cisplatin; Fluorouracil; Cetuximab

Study Results

Participant Flow

Recruitment Details	This study was activated on January 19, 2007, 28 patients were enrolled to arm I (closed to accrual on 11/3/2008) and 35 patients were enrolled to arm II (open to accrual on 8/18/2009).

Arm/Group Title	Arm I (Closed to Accrual as of 11/3/2008)	Arm II (Open to Accrual on 8/18/2009)
Arm/Group Description	Patients receive cisplatin IV over 60 minutes on days 1, 29, 57, and 85 and fluorouracil IV continuously over 96 hours on days 1-4, 29-32, 57-60, and 85-88. Patients also receive cetuximab IV over 120 minutes on day 50 and then IV over 60 minutes on days 57, 64, 71, 78, 85, 92, and 99 and undergo radiotherapy once daily 5 days a week for 5 weeks, beginning on day 57. Treatment continues in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV cisplatin: Given IV fluorouracil: Given IV radiation therapy: Given once daily 5 days a week for 5 weeks	Patients receive cetuximab IV over 120 minutes on day 1 and then IV over 60 minutes on days 8, 15, 22, 29, 36, 43, and 50. Patients also receive cisplatin IV over 60 minutes on days 1 and 36, fluorouracil IV continuously over 96 hours on days 8-11 and 36-39, and undergo radiotherapy once daily 5 days a week for 5 weeks beginning on day 8. Treatment continues in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV cisplatin: Given IV fluorouracil: Given IV radiation therapy: Given once daily 5 days a week for 5 weeks
Period Title: Overall Study
STARTED	28	35
Eligible	28	35
Treated	28	34
Started Induction Chemotherapy	28	0
Started Chemo+Radiation+Cetuximab	27	34
COMPLETED	22	27
NOT COMPLETED	6	8

Baseline Characteristics

Arm/Group Title	Arm I (Closed to Accrual as of 11/3/2008)	Arm II (Open to Accrual on 8/18/2009)	Total
Arm/Group Description	Patients receive cisplatin IV over 60 minutes on days 1, 29, 57, and 85 and fluorouracil IV continuously over 96 hours on days 1-4, 29-32, 57-60, and 85-88. Patients also receive cetuximab IV over 120 minutes on day 50 and then IV over 60 minutes on days 57, 64, 71, 78, 85, 92, and 99 and undergo radiotherapy once daily 5 days a week for 5 weeks, beginning on day 57. Treatment continues in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV cisplatin: Given IV fluorouracil: Given IV radiation therapy: Given once daily 5 days a week for 5 weeks	Patients receive cetuximab IV over 120 minutes on day 1 and then IV over 60 minutes on days 8, 15, 22, 29, 36, 43, and 50. Patients also receive cisplatin IV over 60 minutes on days 1 and 36, fluorouracil IV continuously over 96 hours on days 8-11 and 36-39, and undergo radiotherapy once daily 5 days a week for 5 weeks beginning on day 8. Treatment continues in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV cisplatin: Given IV fluorouracil: Given IV radiation therapy: Given once daily 5 days a week for 5 weeks	Total of all reporting groups
Overall Participants	27	34	61
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	56	56	56
Sex: Female, Male (Count of Participants)
Female	21 77.8%	28 82.4%	49 80.3%
Male	6 22.2%	6 17.6%	12 19.7%

Outcome Measures

1. Primary Outcome

Title	Local Failure Rate at 3 Years
Description	Local failure was defined as progression/relapse of disease in the anal canal and/or regional organs and/or regional lymph nodes after completion of protocol therapy, or progression during protocol therapy. Lost to follow-up and death (regardless of cause of death) prior to 3 years were also considered as local failures. For the calculation of local failure rate at 3 years, patients were classified into two groups (ie, coded as binary variable): failure (patients with local failure events prior to 3 years) vs. no failure (patients who still alive and had no local failure at 3 years). The binomial proportion and its exact two-sided 80% confidence interval (CI) were used to estimate it.
Time Frame	assessed every 3 months for patients within 2 years of registration, then every 6 months for patients in year 3

Outcome Measure Data

Analysis Population Description

eligible and treated patients

Arm/Group Title	Arm I (Closed to Accrual as of 11/3/2008)	Arm II (Open to Accrual on 8/18/2009)
Arm/Group Description	Patients receive cisplatin IV over 60 minutes on days 1, 29, 57, and 85 and fluorouracil IV continuously over 96 hours on days 1-4, 29-32, 57-60, and 85-88. Patients also receive cetuximab IV over 120 minutes on day 50 and then IV over 60 minutes on days 57, 64, 71, 78, 85, 92, and 99 and undergo radiotherapy once daily 5 days a week for 5 weeks, beginning on day 57. Treatment continues in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV cisplatin: Given IV fluorouracil: Given IV radiation therapy: Given once daily 5 days a week for 5 weeks	Patients receive cetuximab IV over 120 minutes on day 1 and then IV over 60 minutes on days 8, 15, 22, 29, 36, 43, and 50. Patients also receive cisplatin IV over 60 minutes on days 1 and 36, fluorouracil IV continuously over 96 hours on days 8-11 and 36-39, and undergo radiotherapy once daily 5 days a week for 5 weeks beginning on day 8. Treatment continues in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV cisplatin: Given IV fluorouracil: Given IV radiation therapy: Given once daily 5 days a week for 5 weeks
Measure Participants	27	34
Number (80% Confidence Interval) [proportion of participants]	0.259 1%	0.353 1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Closed to Accrual as of 11/3/2008)
	Comments	Null hypothesis is that the local failure rate at 3 years is no more than 35%.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.218
	Comments
	Method	one sample binomial test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm II (Open to Accrual on 8/18/2009)
	Comments	The null hypothesis is that the local failure rate at 3 years is no more than 35%.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.592
	Comments
	Method	one sample binomial test
	Comments

2. Secondary Outcome

Title	3-year Overall Survival Rate
Description	Overall survival (OS) is defined as time from registration to death from any cause. Patients alive are censored at the last contact date. Kaplan-Meier method was used to estimate the 3-year OS rate.
Time Frame	assessed every 3 months for patients within 2 years of registration, then every 6 months for patients in year 3

Outcome Measure Data

Analysis Population Description

eligible and treated patients

Arm/Group Title	Arm I (Closed to Accrual as of 11/3/2008)	Arm II (Open to Accrual on 8/18/2009)
Arm/Group Description	Patients receive cisplatin IV over 60 minutes on days 1, 29, 57, and 85 and fluorouracil IV continuously over 96 hours on days 1-4, 29-32, 57-60, and 85-88. Patients also receive cetuximab IV over 120 minutes on day 50 and then IV over 60 minutes on days 57, 64, 71, 78, 85, 92, and 99 and undergo radiotherapy once daily 5 days a week for 5 weeks, beginning on day 57. Treatment continues in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV cisplatin: Given IV fluorouracil: Given IV radiation therapy: Given once daily 5 days a week for 5 weeks	Patients receive cetuximab IV over 120 minutes on day 1 and then IV over 60 minutes on days 8, 15, 22, 29, 36, 43, and 50. Patients also receive cisplatin IV over 60 minutes on days 1 and 36, fluorouracil IV continuously over 96 hours on days 8-11 and 36-39, and undergo radiotherapy once daily 5 days a week for 5 weeks beginning on day 8. Treatment continues in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV cisplatin: Given IV fluorouracil: Given IV radiation therapy: Given once daily 5 days a week for 5 weeks
Measure Participants	27	34
Number (95% Confidence Interval) [proportion of participants]	0.887 3.3%	0.789 2.3%

3. Secondary Outcome

Title	3-year Progression-free Survival Rate
Description	Progression-free survival (PFS) was defined as time from registration to disease progression, relapse or death (whichever occurred first), censoring cases without PFS events at the date of last disease assessment documenting the patient was free of progression/relapse. Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Kaplan-Meier method was used to estimate the 3-year PFS rate.
Time Frame	assessed every 3 months for patients within 2 years of registration, then every 6 months for patients in year 3

Outcome Measure Data

Analysis Population Description

eligible and treated patients

Arm/Group Title	Arm I (Closed to Accrual as of 11/3/2008)	Arm II (Open to Accrual on 8/18/2009)
Arm/Group Description	Patients receive cisplatin IV over 60 minutes on days 1, 29, 57, and 85 and fluorouracil IV continuously over 96 hours on days 1-4, 29-32, 57-60, and 85-88. Patients also receive cetuximab IV over 120 minutes on day 50 and then IV over 60 minutes on days 57, 64, 71, 78, 85, 92, and 99 and undergo radiotherapy once daily 5 days a week for 5 weeks, beginning on day 57. Treatment continues in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV cisplatin: Given IV fluorouracil: Given IV radiation therapy: Given once daily 5 days a week for 5 weeks	Patients receive cetuximab IV over 120 minutes on day 1 and then IV over 60 minutes on days 8, 15, 22, 29, 36, 43, and 50. Patients also receive cisplatin IV over 60 minutes on days 1 and 36, fluorouracil IV continuously over 96 hours on days 8-11 and 36-39, and undergo radiotherapy once daily 5 days a week for 5 weeks beginning on day 8. Treatment continues in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV cisplatin: Given IV fluorouracil: Given IV radiation therapy: Given once daily 5 days a week for 5 weeks
Measure Participants	27	34
Number (95% Confidence Interval) [proportion of participants]	0.809 3%	0.616 1.8%

4. Secondary Outcome

Title	Objective Response Rate
Description	Objective response rate is defined as number of patients with complete response (CR) or partial response (PR) divided by all eligible and treated patients. Responses are evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline. CR is defined as disappearance of all target and non-target lesions. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameters), and/or persistence of one or more non-target lesion(s).
Time Frame	Tumor assessments were made at baseline, within 4 weeks of the completion of protocol treatment, then every 6 months if patient was 1-4 years from registration, yearly if patient was 5-10 years from registration until progression/relapse using the RECIST

Outcome Measure Data

Analysis Population Description

eligible and treated patients

Arm/Group Title	Arm I (Closed to Accrual as of 11/3/2008)	Arm II (Open to Accrual on 8/18/2009)
Arm/Group Description	Patients receive cisplatin IV over 60 minutes on days 1, 29, 57, and 85 and fluorouracil IV continuously over 96 hours on days 1-4, 29-32, 57-60, and 85-88. Patients also receive cetuximab IV over 120 minutes on day 50 and then IV over 60 minutes on days 57, 64, 71, 78, 85, 92, and 99 and undergo radiotherapy once daily 5 days a week for 5 weeks, beginning on day 57. Treatment continues in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV cisplatin: Given IV fluorouracil: Given IV radiation therapy: Given once daily 5 days a week for 5 weeks	Patients receive cetuximab IV over 120 minutes on day 1 and then IV over 60 minutes on days 8, 15, 22, 29, 36, 43, and 50. Patients also receive cisplatin IV over 60 minutes on days 1 and 36, fluorouracil IV continuously over 96 hours on days 8-11 and 36-39, and undergo radiotherapy once daily 5 days a week for 5 weeks beginning on day 8. Treatment continues in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV cisplatin: Given IV fluorouracil: Given IV radiation therapy: Given once daily 5 days a week for 5 weeks
Measure Participants	27	34
Number (95% Confidence Interval) [proportion of participants]	0.630 2.3%	0.647 1.9%

5. Secondary Outcome

Title	3-year Colostomy-free Survival Rate
Description	Colostomy-free survival was defined as time from registration until time of colostomy or death without colostomy, censoring cases without colostomy at the data of last disease assessment documenting the patient was free of colostomy. Kaplan-Meier method was used to estimate the 3-year colostomy-free survival rate.
Time Frame	assessed every 3 months for patients within 2 years of registration, then every 6 months for patients in year 3

Outcome Measure Data

Analysis Population Description

eligible and treated patients who did not have permanent colostomy at study entry

Arm/Group Title	Arm I (Closed to Accrual as of 11/3/2008)	Arm II (Open to Accrual on 8/18/2009)
Arm/Group Description	Patients receive cisplatin IV over 60 minutes on days 1, 29, 57, and 85 and fluorouracil IV continuously over 96 hours on days 1-4, 29-32, 57-60, and 85-88. Patients also receive cetuximab IV over 120 minutes on day 50 and then IV over 60 minutes on days 57, 64, 71, 78, 85, 92, and 99 and undergo radiotherapy once daily 5 days a week for 5 weeks, beginning on day 57. Treatment continues in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV cisplatin: Given IV fluorouracil: Given IV radiation therapy: Given once daily 5 days a week for 5 weeks	Patients receive cetuximab IV over 120 minutes on day 1 and then IV over 60 minutes on days 8, 15, 22, 29, 36, 43, and 50. Patients also receive cisplatin IV over 60 minutes on days 1 and 36, fluorouracil IV continuously over 96 hours on days 8-11 and 36-39, and undergo radiotherapy once daily 5 days a week for 5 weeks beginning on day 8. Treatment continues in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV cisplatin: Given IV fluorouracil: Given IV radiation therapy: Given once daily 5 days a week for 5 weeks
Measure Participants	27	34
Number (95% Confidence Interval) [proportion of participants]	0.849 3.1%	0.657 1.9%

Adverse Events

Time Frame	Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Arm/Group Title	Arm I (Closed to Accrual as of 11/3/2008)		Arm II (Open to Accrual on 8/18/2009)
Arm/Group Description	Patients receive cisplatin IV over 60 minutes on days 1, 29, 57, and 85 and fluorouracil IV continuously over 96 hours on days 1-4, 29-32, 57-60, and 85-88. Patients also receive cetuximab IV over 120 minutes on day 50 and then IV over 60 minutes on days 57, 64, 71, 78, 85, 92, and 99 and undergo radiotherapy once daily 5 days a week for 5 weeks, beginning on day 57. Treatment continues in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV cisplatin: Given IV fluorouracil: Given IV radiation therapy: Given once daily 5 days a week for 5 weeks		Patients receive cetuximab IV over 120 minutes on day 1 and then IV over 60 minutes on days 8, 15, 22, 29, 36, 43, and 50. Patients also receive cisplatin IV over 60 minutes on days 1 and 36, fluorouracil IV continuously over 96 hours on days 8-11 and 36-39, and undergo radiotherapy once daily 5 days a week for 5 weeks beginning on day 8. Treatment continues in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV cisplatin: Given IV fluorouracil: Given IV radiation therapy: Given once daily 5 days a week for 5 weeks
All Cause Mortality
	Arm I (Closed to Accrual as of 11/3/2008)		Arm II (Open to Accrual on 8/18/2009)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I (Closed to Accrual as of 11/3/2008)		Arm II (Open to Accrual on 8/18/2009)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/28 (92.9%)		29/34 (85.3%)
Blood and lymphatic system disorders
Anemia	2/28 (7.1%)		5/34 (14.7%)
Febrile neutropenia	0/28 (0%)		1/34 (2.9%)
Cardiac disorders
Left ventricular systolic dysfunction	0/28 (0%)		1/34 (2.9%)
Ear and labyrinth disorders
Tinnitus	1/28 (3.6%)		0/34 (0%)
Gastrointestinal disorders
Diarrhea w/o prior colostomy	15/28 (53.6%)		23/34 (67.6%)
Dry mouth	1/28 (3.6%)		0/34 (0%)
Malabsorption	1/28 (3.6%)		0/34 (0%)
Muco/stomatitis by exam, oral cavity	1/28 (3.6%)		3/34 (8.8%)
Muco/stomatitis (symptom) esophagus	0/28 (0%)		1/34 (2.9%)
Muco/stomatitis (symptom) oral cavity	2/28 (7.1%)		1/34 (2.9%)
Muco/stomatitis (symptom) rectum	1/28 (3.6%)		0/34 (0%)
Nausea	7/28 (25%)		11/34 (32.4%)
Vomiting	2/28 (7.1%)		5/34 (14.7%)
Rectum, hemorrhage	1/28 (3.6%)		0/34 (0%)
Abdomen, pain	1/28 (3.6%)		3/34 (8.8%)
Anus, pain	1/28 (3.6%)		2/34 (5.9%)
Rectum, pain	2/28 (7.1%)		1/34 (2.9%)
General disorders
Fatigue	6/28 (21.4%)		7/34 (20.6%)
Immune system disorders
Allergic reaction	0/28 (0%)		1/34 (2.9%)
Infections and infestations
Infection w/ gr3-4 neut, lung	0/28 (0%)		1/34 (2.9%)
Infection Gr0-2 neut, bladder	1/28 (3.6%)		2/34 (5.9%)
Infection Gr0-2 neut, rectum	1/28 (3.6%)		0/34 (0%)
Infection Gr0-2 neut, blood	0/28 (0%)		1/34 (2.9%)
Infection w/ unk ANC blood	1/28 (3.6%)		1/34 (2.9%)
Injury, poisoning and procedural complications
Chemoradiation dermatitis	4/28 (14.3%)		0/34 (0%)
Radiation dermatitis	3/28 (10.7%)		1/34 (2.9%)
Investigations
Leukocytes decreased	7/28 (25%)		14/34 (41.2%)
Lymphopenia	3/28 (10.7%)		6/34 (17.6%)
Neutrophils decreased	6/28 (21.4%)		17/34 (50%)
Platelets decreased	2/28 (7.1%)		4/34 (11.8%)
Weight loss	1/28 (3.6%)		1/34 (2.9%)
INR increased	1/28 (3.6%)		0/34 (0%)
Activated partial thromboplastin time prolonged	1/28 (3.6%)		0/34 (0%)
Creatinine increased	0/28 (0%)		1/34 (2.9%)
Metabolism and nutrition disorders
Anorexia	3/28 (10.7%)		7/34 (20.6%)
Dehydration	9/28 (32.1%)		11/34 (32.4%)
Acidosis	1/28 (3.6%)		1/34 (2.9%)
Hypoalbuminemia	1/28 (3.6%)		3/34 (8.8%)
Hypocalcemia	0/28 (0%)		2/34 (5.9%)
Hyperglycemia	0/28 (0%)		1/34 (2.9%)
Hypomagnesemia	2/28 (7.1%)		1/34 (2.9%)
Hypophosphatemia	1/28 (3.6%)		3/34 (8.8%)
Hypokalemia	4/28 (14.3%)		8/34 (23.5%)
Hyponatremia	0/28 (0%)		2/34 (5.9%)
Musculoskeletal and connective tissue disorders
Nonneuropathic generalized weakness	1/28 (3.6%)		0/34 (0%)
Osteoporosis	1/28 (3.6%)		0/34 (0%)
Back, pain	1/28 (3.6%)		0/34 (0%)
Nervous system disorders
Ataxia	0/28 (0%)		1/34 (2.9%)
Dizziness	1/28 (3.6%)		0/34 (0%)
Head/headache	1/28 (3.6%)		1/34 (2.9%)
Renal and urinary disorders
Bladder, pain	0/28 (0%)		1/34 (2.9%)
Cystitis	0/28 (0%)		1/34 (2.9%)
Renal failure	1/28 (3.6%)		1/34 (2.9%)
Renal/GU-other	0/28 (0%)		1/34 (2.9%)
Reproductive system and breast disorders
Scrotum, pain	0/28 (0%)		1/34 (2.9%)
Vaginal mucositis	0/28 (0%)		1/34 (2.9%)
Respiratory, thoracic and mediastinal disorders
Muco/stomatitis (symptom) pharynx	1/28 (3.6%)		0/34 (0%)
Dyspnea	0/28 (0%)		1/34 (2.9%)
Pneumonitis/pulmonary infiltrates	0/28 (0%)		1/34 (2.9%)
Pulmonary/Upper Respiratory-other	1/28 (3.6%)		0/34 (0%)
Skin and subcutaneous tissue disorders
Rash/desquamation	0/28 (0%)		1/34 (2.9%)
Rash: acne/acneiform	0/28 (0%)		2/34 (5.9%)
Ulceration	1/28 (3.6%)		1/34 (2.9%)
Skin, pain	2/28 (7.1%)		0/34 (0%)
Vascular disorders
Thrombosis/thrombus/embolism	1/28 (3.6%)		2/34 (5.9%)
Other (Not Including Serious) Adverse Events
	Arm I (Closed to Accrual as of 11/3/2008)		Arm II (Open to Accrual on 8/18/2009)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	28/28 (100%)		34/34 (100%)
Blood and lymphatic system disorders
Anemia	11/28 (39.3%)		12/34 (35.3%)
Cardiac disorders
Sinus tachycardia	0/28 (0%)		2/34 (5.9%)
Ear and labyrinth disorders
Tinnitus	3/28 (10.7%)		1/34 (2.9%)
Eye disorders
Vision-blurred	2/28 (7.1%)		0/34 (0%)
Tearing	2/28 (7.1%)		0/34 (0%)
Gastrointestinal disorders
Constipation	7/28 (25%)		7/34 (20.6%)
Diarrhea w/o prior colostomy	15/28 (53.6%)		9/34 (26.5%)
Dysphagia	2/28 (7.1%)		0/34 (0%)
Dyspepsia	5/28 (17.9%)		0/34 (0%)
Muco/stomatitis by exam, oral cavity	12/28 (42.9%)		9/34 (26.5%)
Muco/stomatitis (symptom) oral cavity	9/28 (32.1%)		10/34 (29.4%)
Nausea	23/28 (82.1%)		19/34 (55.9%)
Proctitis	0/28 (0%)		2/34 (5.9%)
Vomiting	17/28 (60.7%)		13/34 (38.2%)
Rectum, hemorrhage	2/28 (7.1%)		2/34 (5.9%)
Abdomen, pain	3/28 (10.7%)		4/34 (11.8%)
Anus, pain	1/28 (3.6%)		2/34 (5.9%)
Rectum, pain	7/28 (25%)		4/34 (11.8%)
General disorders
Fatigue	23/28 (82.1%)		23/34 (67.6%)
Fever w/o neutropenia	4/28 (14.3%)		6/34 (17.6%)
Edema limb	2/28 (7.1%)		0/34 (0%)
Injury, poisoning and procedural complications
Burn	4/28 (14.3%)		5/34 (14.7%)
Chemoradiation dermatitis	2/28 (7.1%)		1/34 (2.9%)
Radiation dermatitis	1/28 (3.6%)		4/34 (11.8%)
Investigations
Leukocytes decreased	15/28 (53.6%)		11/34 (32.4%)
Lymphopenia	2/28 (7.1%)		1/34 (2.9%)
Neutrophils decreased	11/28 (39.3%)		7/34 (20.6%)
Platelets decreased	11/28 (39.3%)		14/34 (41.2%)
Weight loss	11/28 (39.3%)		25/34 (73.5%)
Alkaline phosphatase increased	1/28 (3.6%)		4/34 (11.8%)
Alanine aminotransferase increased	1/28 (3.6%)		2/34 (5.9%)
Aspartate aminotransferase increased	1/28 (3.6%)		2/34 (5.9%)
Creatinine increased	4/28 (14.3%)		3/34 (8.8%)
Metabolism and nutrition disorders
Anorexia	15/28 (53.6%)		13/34 (38.2%)
Dehydration	2/28 (7.1%)		5/34 (14.7%)
Hypoalbuminemia	4/28 (14.3%)		9/34 (26.5%)
Hypocalcemia	4/28 (14.3%)		8/34 (23.5%)
Hyperglycemia	2/28 (7.1%)		3/34 (8.8%)
Hypomagnesemia	17/28 (60.7%)		21/34 (61.8%)
Hypokalemia	4/28 (14.3%)		5/34 (14.7%)
Hyponatremia	3/28 (10.7%)		7/34 (20.6%)
Musculoskeletal and connective tissue disorders
Nonneuropathic generalized weakness	1/28 (3.6%)		2/34 (5.9%)
Nervous system disorders
Taste disturbance	8/28 (28.6%)		5/34 (14.7%)
Dizziness	3/28 (10.7%)		1/34 (2.9%)
Neuropathy-sensory	5/28 (17.9%)		3/34 (8.8%)
Head/headache	7/28 (25%)		2/34 (5.9%)
Psychiatric disorders
Insomnia	1/28 (3.6%)		4/34 (11.8%)
Anxiety	0/28 (0%)		2/34 (5.9%)
Renal and urinary disorders
Urethra, pain	2/28 (7.1%)		0/34 (0%)
Reproductive system and breast disorders
Vaginitis (not due to infection)	0/28 (0%)		2/34 (5.9%)
Respiratory, thoracic and mediastinal disorders
Muco/stomatitis by exam, pharynx	1/28 (3.6%)		2/34 (5.9%)
Skin and subcutaneous tissue disorders
Dry skin	9/28 (32.1%)		7/34 (20.6%)
Alopecia	9/28 (32.1%)		5/34 (14.7%)
Pruritus/itching	3/28 (10.7%)		2/34 (5.9%)
Rash/desquamation	2/28 (7.1%)		2/34 (5.9%)
Rash: acne/acneiform	15/28 (53.6%)		19/34 (55.9%)
Hand-foot reaction	2/28 (7.1%)		0/34 (0%)
Ulceration	4/28 (14.3%)		2/34 (5.9%)
Vascular disorders
Hypertension	0/28 (0%)		3/34 (8.8%)
Hypotension	2/28 (7.1%)		2/34 (5.9%)

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.