Capecitabine, Oxaliplatin, and Radiation Therapy in Treating Patients Who Are Undergoing Surgery for Stage I Rectal Cancer

• Sponsor: Alliance for Clinical Trials in Oncology (Other)
• Overall Status: Completed
• CT.gov ID: NCT00114231
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 90
• Locations: 67
• Arm: 1
• Duration (Months): 103
• Patients Per Site: 1.3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as capecitabine and oxaliplatin, 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. Oxaliplatin may make tumor cells more sensitive to radiation therapy. Giving capecitabine and oxaliplatin together with radiation therapy before surgery may shrink the tumor so it can be removed.

PURPOSE: This phase II trial is studying how well giving capecitabine and oxaliplatin together with radiation therapy works in treating patients who are undergoing surgery for stage I rectal cancer.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer	Drug: capecitabine; Drug: oxaliplatin; Procedure: neoadjuvant therapy; Radiation: radiation therapy	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Determine the 3-year disease-free survival rate in patients with stage I adenocarcinoma of the rectum treated with neoadjuvant chemoradiotherapy comprising capecitabine, oxaliplatin, and radiotherapy followed by local excision.

Secondary

• Determine the rate of resectability with negative resection margins in patients treated with this regimen.

• Determine the procedure-specific morbidity and mortality in patients treated with this regimen.

• Determine the rate of pathologic complete response of the primary tumor in patients treated with this regimen.

• Determine the impact of this regimen on anorectal function and quality of life in these patients.

• Determine the feasibility of using molecular studies to assess surgical resection margins and tumor response in patients treated with this regimen.

• Determine molecular markers associated with local tumor recurrence in patients treated with this regimen.

OUTLINE: This is a non-randomized, multicenter study.

Patients undergo high-dose external beam radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, and 29-33. Patients also receive oral capecitabine twice daily on days 1-14 and 22-35 and oxaliplatin IV over 2 hours on days 1, 8, 22, and 29. Approximately 4-8 weeks after completion of chemoradiotherapy, patients undergo local excision of the tumor. Patients with T3 disease or positive resection margins after local excision undergo radical resection of the rectum and receive additional chemotherapy and/or radiotherapy at the discretion of the physician.

Quality of life is assessed at baseline and then 1 year after surgery.

After completion of study treatment, patients are followed at 1 month, every 4 months for 3 years, and then every 6 months for 2 years.

PROJECTED ACCRUAL: A total of 102 patients will be accrued for this study within 2.8 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 90 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Chemoradiotherapy and Local Excision for uT2uN0 Rectal Cancer
• Study Start Date: May 1, 2006
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (capecitabine, oxaliplatin, radiotherapy, surgery) Patients undergo high-dose external beam radiotherapy once daily and receive capecitabine PO BID on days 1-5, 8-12, 15-19, 22-26, and 29-33. Patients also receive oxaliplatin IV over 2 hours on days 1, 8, 22, and 29. Approximately 4-8 weeks after completion of chemoradiotherapy, patients undergo local excision of the tumor. Patients with T3 disease or positive resection margins after local excision undergo radical resection of the rectum and receive additional chemotherapy and/or radiotherapy at the discretion of the physician.

Drug: capecitabine; Other Names: Given IV ; Drug: oxaliplatin; Given IV; Procedure: neoadjuvant therapy; Undergo surgery; Other Names: therapeutic conventional surgery ; Radiation: radiation therapy; Undergo radiotherapy; Other Names: irradiation, radiotherapy, therapy, radiation

Outcome Measures

Primary Outcome Measures

1. 3-Year Disease-free Survival [Up to 3 years]

   The primary endpoint was 3-year disease-free survival (DFS). Evidence of local recurrence, distant metastasis, or death from any cause within 3 years counted as events in the time-to-event Kaplan-Meier analysis of disease-free survival.

Secondary Outcome Measures

1. R0 Resection Rate (Negative Margin Rate) [At time of surgery]

   The rate (percentage) of patients with negative resection margins after undergoing local excision is reported below.

2. Morbidity and Mortality Rate [Up to 30 days]

   Morbidity and mortality after neoadjuvant cheoradiotherapy and local excision.

3. Rate of Pathologic Complete Response of the Primary Tumor [Up to 5 years]

   The rate (percentage) of patients with pathologic complete response (pCR) is reported below. Pathologic response will be determined by comparing tumor width and stage in the surgical specimen with the same parameters as determined by pre-CRT ERUS: PATHOLOGIC COMPLETE RESPONSE (pCR): no residual tumor.

4. Local Recurrence Rate [Up to 5 years]

   The local recurrence rate (percentage) is defined as the percentage of patients who had local recurrence as initial sites of failure at the end of follow-up.

Eligibility Criteria

Criteria

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

• Patient must have an Eastern Cooperative Oncology Group (ECOG)/Zubrod status of =< 2

• Patient must have histologically confirmed invasive adenocarcinoma of the rectum; Note: patients with rectal tumors suspicious for invasion also are eligible

• Distal border of the patient's tumor must be within 8 cm from the anal verge as measured on endoscopic exam

• Patients with tumors fixed to adjacent structures on digital exam are NOT eligible

• Patient must have an uT2uN0 tumor, as confirmed by endorectal ultrasound (ERUS) or endorectal coil magnetic resonance imaging (MRI) scan; patients with uT1, uT3, or uT4 tumors are NOT eligible; greatest diameter of tumor cannot exceed 4 cm

• Patients with positive perirectal nodes on ERUS examination are NOT eligible

• Patients with histologic evidence of metastatic invasion of inguinal lymph nodes are NOT eligible

• Patients with the following conditions are NOT allowed on study:

• Metastatic disease or other primaries (patient must have had chest X-ray/computed tomography [CT] and abdominal & pelvic CT/MRI with IV contrast, as well as a colonoscopy)

• Previously documented history of familial adenomatous polyposis

• Previously documented history of hereditary non-polyposis colorectal cancer diagnosed clinically (Amsterdam II criteria) or by genetic testing

• History of inflammatory bowel disease

• History of prior radiation treatments to pelvis

• Clinically significant peripheral sensory or motor neuropathy (defined as symptomatic weakness, paresthesia or sensory alteration described to be interfering with function, interfering with activities of daily living, disabling or life-threatening)

• History of any clinically significant cardiac disease (i.e., class 3-4 congestive heart failure, symptomatic coronary artery disease, uncontrolled arrhythmia, and/or myocardial infarction within the last 6 months)

• History of uncontrolled seizures or clinically significant central nervous system disorders

• History of psychiatric conditions or diminished mental capacity that could compromise the giving of informed consent, or interfere with study compliance

• History of allergy and/or hypersensitivity to capecitabine and/or oxaliplatin

• History of difficulty or inability to take or absorb oral medications

• White blood cells (WBC) >= 3000/mm^3

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

• Hemoglobin > 9.5 mg/dl

• Platelet count >= 100,000/mm^3

• Total bilirubin =< 3 mg/dl

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.0 times institutional upper limit of normal (ULN)

• Alkaline phosphatase =< 2.0 times ULN

• Creatinine clearance (CLcr) >= 50 ml/min by Cockroft-Gault equation

• Patients who have experienced a prior malignancy must have received potentially curative therapy for that malignancy, and must be cancer-free for at least five years from the date of initial diagnosis (exceptions: patients treated for non-melanoma skin carcinoma, or in-situ carcinomas)

• Patients of reproductive potential must agree to use an effective method of birth control when undergoing treatments with known or possible mutagenic or teratogenic effects; all female participants of childbearing potential must have a negative urine or serum pregnancy test within two weeks prior to study registration

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Scottsdale	Scottsdale	Arizona	United States	85259-5499
2	Cancer Care Center at John Muir Health - Concord Campus	Concord	California	United States	94524-4110
3	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010-3000
4	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California	United States	90089-9181
5	Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center	Orange	California	United States	92868
6	John Muir/Mt. Diablo Comprehensive Cancer Center	Walnut Creek	California	United States	94598
7	St. Vincent's Medical Center	Bridgeport	Connecticut	United States	06606
8	Praxair Cancer Center at Danbury Hospital	Danbury	Connecticut	United States	06810
9	Mayo Clinic - Jacksonville	Jacksonville	Florida	United States	32224
10	Tampa General Hospital	Tampa	Florida	United States	33606
11	Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center	Savannah	Georgia	United States	31403-3089
12	Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler	Savannah	Georgia	United States	31405
13	University of Chicago Cancer Research Center	Chicago	Illinois	United States	60637-1470
14	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana	United States	46107
15	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana	United States	46202-5289
16	William N. Wishard Memorial Hospital	Indianapolis	Indiana	United States	46202
17	Reid Hospital & Health Care Services	Richmond	Indiana	United States	47374
18	Ochsner Cancer Institute at Ochsner Clinic Foundation	New Orleans	Louisiana	United States	70121
19	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
20	Altru Cancer Center at Altru Hospital	Grand Forks	North Dakota	United States	58201
21	Grandview Hospital	Dayton	Ohio	United States	45405
22	Good Samaritan Hospital	Dayton	Ohio	United States	45406
23	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio	United States	45409
24	Samaritan North Cancer Care Center	Dayton	Ohio	United States	45415
25	Veterans Affairs Medical Center - Dayton	Dayton	Ohio	United States	45428
26	CCOP - Dayton	Dayton	Ohio	United States	45429
27	Blanchard Valley Medical Associates	Findlay	Ohio	United States	45840
28	Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
29	Wayne Hospital	Greenville	Ohio	United States	45331
30	Charles F. Kettering Memorial Hospital	Kettering	Ohio	United States	45429
31	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio	United States	45373-1300
32	Clinton Memorial Hospital	Wilmington	Ohio	United States	45177
33	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio	United States	45385
34	Integris Oncology Services	Oklahoma City	Oklahoma	United States	73112
35	Natalie Warren Bryant Cancer Center at St. Francis Hospital	Tulsa	Oklahoma	United States	74136
36	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon	United States	97213-2967
37	Knight Cancer Institute at Oregon Health and Science University	Portland	Oregon	United States	97239-3098
38	Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest	Allentown	Pennsylvania	United States	18105
39	UPMC Cancer Center at Beaver Medical Center	Beaver	Pennsylvania	United States	15009
40	UPMC Cancer Center at Jefferson Regional Medical Center	Clairton	Pennsylvania	United States	15025
41	UPMC Cancer Center - Arnold Palmer Pavilion	Greensburg	Pennsylvania	United States	15601
42	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033-0850
43	UPMC Cancer Center at the John P. Murtha Pavilion	Johnstown	Pennsylvania	United States	15901
44	UPMC - Moon	Moon	Pennsylvania	United States	15108
45	UPMC Cancer Center - Natrona Heights	Natrona Heights	Pennsylvania	United States	15065
46	Jameson Memorial Hospital - North Campus	New Castle	Pennsylvania	United States	16105
47	Fox Chase Cancer Center - Philadelphia	Philadelphia	Pennsylvania	United States	19111-2497
48	Allegheny Cancer Center at Allegheny General Hospital	Pittsburgh	Pennsylvania	United States	15212
49	UPMC - Shadyside	Pittsburgh	Pennsylvania	United States	15213-2582
50	UPMC Cancer Center at Magee-Womens Hospital	Pittsburgh	Pennsylvania	United States	15213
51	UPMC Cancer Center at UPMC Presbyterian	Pittsburgh	Pennsylvania	United States	15213
52	UPMC Cancer Center at UPMC St. Margaret	Pittsburgh	Pennsylvania	United States	15215
53	Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital	Pittsburgh	Pennsylvania	United States	15224-1791
54	UPMC Cancer Centers	Pittsburgh	Pennsylvania	United States	15232
55	UPMC Cancer Center at UPMC Passavant	Pittsburgh	Pennsylvania	United States	15237
56	St. Clair Memorial Hospital Cancer Center	Pittsburgh	Pennsylvania	United States	15243
57	UPMC Cancer Center at UPMC Northwest	Seneca	Pennsylvania	United States	16346
58	Washington Hospital Cancer Center	Washington	Pennsylvania	United States	15301
59	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee	United States	37232-6838
60	M. D. Anderson Cancer Center at University of Texas	Houston	Texas	United States	77030-4009
61	Methodist Hospital	Houston	Texas	United States	77030
62	Surgical Oncology Associates	Newport News	Virginia	United States	23606
63	Providence Cancer Center at Sacred Heart Medical Center	Spokane	Washington	United States	99204
64	Providence Cancer Center at Holy Family Hospital	Spokane	Washington	United States	99207
65	United Hospital Center	Clarksburg	West Virginia	United States	26301
66	Edwards Comprehensive Cancer Center at Cabell Huntington Hospital	Huntington	West Virginia	United States	25701
67	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Madison	Wisconsin	United States	53792-6164

Sponsors and Collaborators

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

Investigators

• Study Chair: Julio Garcia-Aguilar, MD, PhD, City of Hope Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

• Ota DM, Nelson H; ACOSOG Group Co-Chairs. Local excision of rectal cancer revisited: ACOSOG protocol Z6041. Ann Surg Oncol. 2007 Feb;14(2):271. Epub 2006 Nov 14.

• Responsible Party: Alliance for Clinical Trials in Oncology
• ClinicalTrials.gov Identifier: NCT00114231
• Other Study ID Numbers: ACOSOG-Z6041; ACOSOG-Z6041; U10CA180821; U10CA076001; CDR0000433145
• First Posted: Jun 14, 2005
• Last Update Posted: Mar 29, 2018
• Last Verified: Feb 1, 2018

• Keywords provided by Alliance for Clinical Trials in Oncology: adenocarcinoma of the rectum; stage I rectal cancer
• Additional relevant MeSH terms: Rectal Neoplasms; Capecitabine; Oxaliplatin

Study Results

Participant Flow

Arm/Group Title	Original Dose Group	Revised Dose Group
Arm/Group Description	External beam radiotherapy with megavoltage linear accelerators (≥ 6 MV) was delivered to a 3-4 field pelvis arrangement after CT-based simulation and computer-assisted treatment planning. Intensity-modulated radiotherapy was allowed. The original dose of radiotherapy was 1·8 Gy per day, 5 days a week for 5 weeks to a dose of 45 Gy to planning target volume 1, then a boost of 9 Gy to planning target volume 2 (defi ned as the gross tumour volume plus 2 cm) for a total dose of 54 Gy. This was accompanied by capecitabine (825 mg/m², twice daily, on days 1-14 and 22-35) and oxaliplatin (50 mg/m² on weeks 1, 2, 4, and 5). Surgery was done 4-8 weeks after completion of neoadjuvant chemoradiotherapy. Local excision was done using conventional transanal excision or transanal endoscopic microsurgery. Full-thickness excision of the tumour with a 1 cm surrounding margin of normal rectal wall was needed.	The radiotherapy was reduced to a total of 50·4 Gy by reducing the 9 Gy boost to 5·4 Gy, and capecitabine was reduced to 725 mg/m², twice daily, 5 days a week for 5 weeks. The dose of oxaliplatin was not changed. Surgery was done 4-8 weeks after completion of neoadjuvant chemoradiotherapy. Local excision was done using conventional transanal excision or transanal endoscopic microsurgery. Full-thickness excision of the tumour with a 1 cm surrounding margin of normal rectal wall was needed.
Period Title: Overall Study
STARTED	62	28
COMPLETED	53	26
NOT COMPLETED	9	2

Baseline Characteristics

Arm/Group Title	Original Dose Group	Revised Dose Group	Total
Arm/Group Description	External beam radiotherapy with megavoltage linear accelerators (≥ 6 MV) was delivered to a 3-4 field pelvis arrangement after CT-based simulation and computer-assisted treatment planning. Intensity-modulated radiotherapy was allowed. The original dose of radiotherapy was 1·8 Gy per day, 5 days a week for 5 weeks to a dose of 45 Gy to planning target volume 1, then a boost of 9 Gy to planning target volume 2 (defi ned as the gross tumour volume plus 2 cm) for a total dose of 54 Gy. This was accompanied by capecitabine (825 mg/m², twice daily, on days 1-14 and 22-35) and oxaliplatin (50 mg/m² on weeks 1, 2, 4, and 5). Surgery was done 4-8 weeks after completion of neoadjuvant chemoradiotherapy. Local excision was done using conventional transanal excision or transanal endoscopic microsurgery. Full-thickness excision of the tumour with a 1 cm surrounding margin of normal rectal wall was needed.	The radiotherapy was reduced to a total of 50·4 Gy by reducing the 9 Gy boost to 5·4 Gy, and capecitabine was reduced to 725 mg/m², twice daily, 5 days a week for 5 weeks. The dose of oxaliplatin was not changed. Surgery was done 4-8 weeks after completion of neoadjuvant chemoradiotherapy. Local excision was done using conventional transanal excision or transanal endoscopic microsurgery. Full-thickness excision of the tumour with a 1 cm surrounding margin of normal rectal wall was needed.	Total of all reporting groups
Overall Participants	53	26	79
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	62	63	62
Sex: Female, Male (Count of Participants)
Female	20 37.7%	6 23.1%	26 32.9%
Male	33 62.3%	20 76.9%	53 67.1%
Region of Enrollment (Count of Participants)
United States	53 100%	26 100%	79 100%

Outcome Measures

1. Primary Outcome

Title	3-Year Disease-free Survival
Description	The primary endpoint was 3-year disease-free survival (DFS). Evidence of local recurrence, distant metastasis, or death from any cause within 3 years counted as events in the time-to-event Kaplan-Meier analysis of disease-free survival.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Capecitabine, Oxaliplatin, Radiotherapy, Surgery)
Arm/Group Description	Patients undergo high-dose external beam radiotherapy once daily and receive capecitabine PO BID on days 1-5, 8-12, 15-19, 22-26, and 29-33. Patients also receive oxaliplatin IV over 2 hours on days 1, 8, 22, and 29. Approximately 4-8 weeks after completion of chemoradiotherapy, patients undergo local excision of the tumor. Patients with T3 disease or positive resection margins after local excision undergo radical resection of the rectum and receive additional chemotherapy and/or radiotherapy at the discretion of the physician.
Measure Participants	79
Number (95% Confidence Interval) [percentage of patients]	88.2

2. Secondary Outcome

Title	R0 Resection Rate (Negative Margin Rate)
Description	The rate (percentage) of patients with negative resection margins after undergoing local excision is reported below.
Time Frame	At time of surgery

Outcome Measure Data

Analysis Population Description

Patients who had local excision are included in this analysis.

Arm/Group Title	Treatment (Capecitabine, Oxaliplatin, Radiotherapy, Surgery)
Arm/Group Description	Patients undergo high-dose external beam radiotherapy once daily and receive capecitabine PO BID on days 1-5, 8-12, 15-19, 22-26, and 29-33. Patients also receive oxaliplatin IV over 2 hours on days 1, 8, 22, and 29. Approximately 4-8 weeks after completion of chemoradiotherapy, patients undergo local excision of the tumor. Patients with T3 disease or positive resection margins after local excision undergo radical resection of the rectum and receive additional chemotherapy and/or radiotherapy at the discretion of the physician.
Measure Participants	77
Number [percentage of patients]	98.7

3. Secondary Outcome

Title	Morbidity and Mortality Rate
Description	Morbidity and mortality after neoadjuvant cheoradiotherapy and local excision.
Time Frame	Up to 30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Capecitabine, Oxaliplatin, Radiotherapy, Surgery)
Arm/Group Description	Patients undergo high-dose external beam radiotherapy once daily and receive capecitabine PO BID on days 1-5, 8-12, 15-19, 22-26, and 29-33. Patients also receive oxaliplatin IV over 2 hours on days 1, 8, 22, and 29. Approximately 4-8 weeks after completion of chemoradiotherapy, patients undergo local excision of the tumor. Patients with T3 disease or positive resection margins after local excision undergo radical resection of the rectum and receive additional chemotherapy and/or radiotherapy at the discretion of the physician.
Measure Participants	79
Mortality	6
Morbidity	10

4. Secondary Outcome

Title	Rate of Pathologic Complete Response of the Primary Tumor
Description	The rate (percentage) of patients with pathologic complete response (pCR) is reported below. Pathologic response will be determined by comparing tumor width and stage in the surgical specimen with the same parameters as determined by pre-CRT ERUS: PATHOLOGIC COMPLETE RESPONSE (pCR): no residual tumor.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Patients assessable for pathology results were included in this analysis.

Arm/Group Title	Treatment (Capecitabine, Oxaliplatin, Radiotherapy, Surgery)
Arm/Group Description	Patients undergo high-dose external beam radiotherapy once daily and receive capecitabine PO BID on days 1-5, 8-12, 15-19, 22-26, and 29-33. Patients also receive oxaliplatin IV over 2 hours on days 1, 8, 22, and 29. Approximately 4-8 weeks after completion of chemoradiotherapy, patients undergo local excision of the tumor. Patients with T3 disease or positive resection margins after local excision undergo radical resection of the rectum and receive additional chemotherapy and/or radiotherapy at the discretion of the physician.
Measure Participants	77
Number (95% Confidence Interval) [percentage of patients]	44

5. Secondary Outcome

Title	Local Recurrence Rate
Description	The local recurrence rate (percentage) is defined as the percentage of patients who had local recurrence as initial sites of failure at the end of follow-up.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Capecitabine, Oxaliplatin, Radiotherapy, Surgery)
Arm/Group Description	Patients undergo high-dose external beam radiotherapy once daily and receive capecitabine PO BID on days 1-5, 8-12, 15-19, 22-26, and 29-33. Patients also receive oxaliplatin IV over 2 hours on days 1, 8, 22, and 29. Approximately 4-8 weeks after completion of chemoradiotherapy, patients undergo local excision of the tumor. Patients with T3 disease or positive resection margins after local excision undergo radical resection of the rectum and receive additional chemotherapy and/or radiotherapy at the discretion of the physician.
Measure Participants	79
Number [percentage of patients]	4

Adverse Events

Time Frame	Up to 3 years.
Adverse Event Reporting Description	Each CTCAE term is a unique representation of a specific event used for medical documentation and scientific analysis and is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for those who received at least one dose of CRT. Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, and appear in the SAE table.
Arm/Group Title	Original Dose Group		Revised Dose Group
Arm/Group Description	External beam radiotherapy with megavoltage linear accelerators (≥ 6 MV) was delivered to a 3-4 field pelvis arrangement after CT-based simulation and computer-assisted treatment planning. Intensity-modulated radiotherapy was allowed. The original dose of radiotherapy was 1·8 Gy per day, 5 days a week for 5 weeks to a dose of 45 Gy to planning target volume 1, then a boost of 9 Gy to planning target volume 2 (defi ned as the gross tumour volume plus 2 cm) for a total dose of 54 Gy. This was accompanied by capecitabine (825 mg/m², twice daily, on days 1-14 and 22-35) and oxaliplatin (50 mg/m² on weeks 1, 2, 4, and 5). Surgery was done 4-8 weeks after completion of neoadjuvant chemoradiotherapy. Local excision was done using conventional transanal excision or transanal endoscopic microsurgery. Full-thickness excision of the tumour with a 1 cm surrounding margin of normal rectal wall was needed.		The radiotherapy was reduced to a total of 50·4 Gy by reducing the 9 Gy boost to 5·4 Gy, and capecitabine was reduced to 725 mg/m², twice daily, 5 days a week for 5 weeks. The dose of oxaliplatin was not changed. Surgery was done 4-8 weeks after completion of neoadjuvant chemoradiotherapy. Local excision was done using conventional transanal excision or transanal endoscopic microsurgery. Full-thickness excision of the tumour with a 1 cm surrounding margin of normal rectal wall was needed.
All Cause Mortality
	Original Dose Group		Revised Dose Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/57 (0%)		0/27 (0%)
Serious Adverse Events
	Original Dose Group		Revised Dose Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/57 (10.5%)		2/27 (7.4%)
Blood and lymphatic system disorders
Hemoglobin decreased	0/57 (0%)	0	1/27 (3.7%)	1
Cardiac disorders
Myocardial ischemia	1/57 (1.8%)	1	0/27 (0%)	0
General disorders
Pain	1/57 (1.8%)	1	0/27 (0%)	0
Infections and infestations
Appendicitis	1/57 (1.8%)	1	0/27 (0%)	0
Investigations
Lymphocyte count decreased	1/57 (1.8%)	1	0/27 (0%)	0
Metabolism and nutrition disorders
Dehydration	1/57 (1.8%)	1	0/27 (0%)	0
Serum phosphate decreased	0/57 (0%)	0	1/27 (3.7%)	1
Serum potassium decreased	1/57 (1.8%)	1	0/27 (0%)	0
Vascular disorders
Hematoma	1/57 (1.8%)	1	0/27 (0%)	0
Other (Not Including Serious) Adverse Events
	Original Dose Group		Revised Dose Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	32/57 (56.1%)		25/27 (92.6%)
Blood and lymphatic system disorders
Blood disorder	0/57 (0%)	0	1/27 (3.7%)	1
Hemoglobin decreased	3/57 (5.3%)	8	13/27 (48.1%)	40
Lymphatic disorder	1/57 (1.8%)	1	0/27 (0%)	0
Cardiac disorders
Myocardial ischemia	1/57 (1.8%)	2	0/27 (0%)	0
Sinus tachycardia	0/57 (0%)	0	1/27 (3.7%)	1
Eye disorders
Diplopia	0/57 (0%)	0	1/27 (3.7%)	3
Vision blurred	0/57 (0%)	0	4/27 (14.8%)	8
Gastrointestinal disorders
Abdominal distension	0/57 (0%)	0	1/27 (3.7%)	1
Abdominal pain	1/57 (1.8%)	1	7/27 (25.9%)	10
Anal exam abnormal	0/57 (0%)	0	1/27 (3.7%)	1
Anal hemorrhage	0/57 (0%)	0	1/27 (3.7%)	1
Anal pain	0/57 (0%)	0	3/27 (11.1%)	3
Anal ulcer	1/57 (1.8%)	2	0/27 (0%)	0
Constipation	0/57 (0%)	0	9/27 (33.3%)	15
Diarrhea	20/57 (35.1%)	35	21/27 (77.8%)	73
Dyspepsia	0/57 (0%)	0	1/27 (3.7%)	1
Ear, nose and throat examination abnormal	0/57 (0%)	0	1/27 (3.7%)	1
Endoscopy small intestine abnormal	0/57 (0%)	0	1/27 (3.7%)	1
Enteritis	0/57 (0%)	0	2/27 (7.4%)	5
Fecal incontinence	0/57 (0%)	0	3/27 (11.1%)	5
Flatulence	1/57 (1.8%)	1	0/27 (0%)	0
Hemorrhoids	0/57 (0%)	0	4/27 (14.8%)	7
Ileus	0/57 (0%)	0	1/27 (3.7%)	1
Nausea	8/57 (14%)	10	15/27 (55.6%)	30
Proctitis	0/57 (0%)	0	2/27 (7.4%)	5
Rectal hemorrhage	0/57 (0%)	0	2/27 (7.4%)	3
Rectal pain	6/57 (10.5%)	9	13/27 (48.1%)	39
Rectal ulcer	1/57 (1.8%)	1	0/27 (0%)	0
Stomach pain	0/57 (0%)	0	1/27 (3.7%)	1
Vomiting	4/57 (7%)	5	4/27 (14.8%)	6
General disorders
Chills	0/57 (0%)	0	3/27 (11.1%)	3
Edema limbs	0/57 (0%)	0	1/27 (3.7%)	1
Fatigue	7/57 (12.3%)	14	18/27 (66.7%)	60
Fever	1/57 (1.8%)	1	3/27 (11.1%)	3
Flu-like symptoms	0/57 (0%)	0	1/27 (3.7%)	1
Localized edema	0/57 (0%)	0	1/27 (3.7%)	1
Pain	4/57 (7%)	7	5/27 (18.5%)	6
Infections and infestations
Infection	2/57 (3.5%)	2	1/27 (3.7%)	1
Urinary tract infection	0/57 (0%)	0	1/27 (3.7%)	1
Injury, poisoning and procedural complications
Radiation recall reaction (dermatologic)	6/57 (10.5%)	8	7/27 (25.9%)	16
Rectal anastomotic leak	1/57 (1.8%)	1	0/27 (0%)	0
Wound dehiscence	1/57 (1.8%)	1	1/27 (3.7%)	1
Investigations
Aspartate aminotransferase increased	0/57 (0%)	0	4/27 (14.8%)	4
Bilirubin increased	0/57 (0%)	0	3/27 (11.1%)	5
Creatinine increased	0/57 (0%)	0	1/27 (3.7%)	2
INR increased	0/57 (0%)	0	2/27 (7.4%)	3
Laboratory test abnormal	0/57 (0%)	0	1/27 (3.7%)	1
Leukocyte count decreased	1/57 (1.8%)	1	8/27 (29.6%)	30
Lymphocyte count decreased	2/57 (3.5%)	4	9/27 (33.3%)	29
Neutrophil count decreased	0/57 (0%)	0	5/27 (18.5%)	13
Platelet count decreased	1/57 (1.8%)	2	5/27 (18.5%)	20
Serum cholesterol increased	0/57 (0%)	0	1/27 (3.7%)	1
Weight loss	1/57 (1.8%)	2	5/27 (18.5%)	11
Metabolism and nutrition disorders
Anorexia	3/57 (5.3%)	4	10/27 (37%)	20
Blood glucose increased	3/57 (5.3%)	9	9/27 (33.3%)	28
Blood uric acid increased	0/57 (0%)	0	1/27 (3.7%)	2
Dehydration	3/57 (5.3%)	5	4/27 (14.8%)	4
Serum albumin decreased	0/57 (0%)	0	5/27 (18.5%)	11
Serum calcium decreased	0/57 (0%)	0	4/27 (14.8%)	5
Serum calcium increased	1/57 (1.8%)	1	0/27 (0%)	0
Serum potassium decreased	1/57 (1.8%)	2	3/27 (11.1%)	6
Serum potassium increased	1/57 (1.8%)	1	1/27 (3.7%)	1
Serum sodium decreased	1/57 (1.8%)	1	6/27 (22.2%)	8
Serum sodium increased	1/57 (1.8%)	3	2/27 (7.4%)	2
Musculoskeletal and connective tissue disorders
Bone pain	0/57 (0%)	0	1/27 (3.7%)	1
Muscle weakness	0/57 (0%)	0	1/27 (3.7%)	1
Musculoskeletal disorder	1/57 (1.8%)	1	0/27 (0%)	0
Myalgia	0/57 (0%)	0	2/27 (7.4%)	3
Pain in extremity	2/57 (3.5%)	2	0/27 (0%)	0
Nervous system disorders
Dizziness	1/57 (1.8%)	1	2/27 (7.4%)	2
Headache	0/57 (0%)	0	2/27 (7.4%)	3
Neurological disorder NOS	1/57 (1.8%)	3	2/27 (7.4%)	6
Peripheral motor neuropathy	0/57 (0%)	0	2/27 (7.4%)	4
Peripheral sensory neuropathy	2/57 (3.5%)	3	7/27 (25.9%)	13
Syncope	1/57 (1.8%)	1	0/27 (0%)	0
Taste alteration	0/57 (0%)	0	4/27 (14.8%)	9
Psychiatric disorders
Anxiety	0/57 (0%)	0	2/27 (7.4%)	2
Depression	1/57 (1.8%)	1	1/27 (3.7%)	1
Insomnia	1/57 (1.8%)	1	2/27 (7.4%)	9
Libido decreased	0/57 (0%)	0	1/27 (3.7%)	1
Renal and urinary disorders
Bladder spasm	0/57 (0%)	0	1/27 (3.7%)	1
Cystitis	0/57 (0%)	0	1/27 (3.7%)	1
Glomerular filtration rate decreased	0/57 (0%)	0	1/27 (3.7%)	6
Urethral pain	0/57 (0%)	0	3/27 (11.1%)	7
Urinary frequency	0/57 (0%)	0	9/27 (33.3%)	20
Urinary incontinence	0/57 (0%)	0	1/27 (3.7%)	1
Urinary retention	0/57 (0%)	0	1/27 (3.7%)	1
Urogenital disorder	1/57 (1.8%)	2	1/27 (3.7%)	2
Reproductive system and breast disorders
Erectile dysfunction	0/57 (0%)	0	3/27 (11.1%)	3
Perineal pain	0/57 (0%)	0	2/27 (7.4%)	3
Testicular pain	0/57 (0%)	0	1/27 (3.7%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/57 (1.8%)	2	1/27 (3.7%)	1
Hemorrhage nasal	0/57 (0%)	0	1/27 (3.7%)	1
Pharyngolaryngeal pain	0/57 (0%)	0	1/27 (3.7%)	1
Voice alteration	1/57 (1.8%)	1	0/27 (0%)	0
Skin and subcutaneous tissue disorders
Hand-and-foot syndrome	1/57 (1.8%)	1	2/27 (7.4%)	2
Nail disorder	0/57 (0%)	0	2/27 (7.4%)	4
Rash desquamating	1/57 (1.8%)	1	1/27 (3.7%)	3
Sweating	0/57 (0%)	0	2/27 (7.4%)	2
Urticaria	1/57 (1.8%)	1	0/27 (0%)	0
Vascular disorders
Hemorrhage	0/57 (0%)	0	1/27 (3.7%)	1
Hot flashes	0/57 (0%)	0	1/27 (3.7%)	1
Hypertension	0/57 (0%)	0	3/27 (11.1%)	4
Hypotension	1/57 (1.8%)	1	1/27 (3.7%)	1
Thrombosis	0/57 (0%)	0	1/27 (3.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.