Trial Outcomes & Findings for Capecitabine, Oxaliplatin, and Radiation Therapy in Treating Patients Who Are Undergoing Surgery for Stage I Rectal Cancer (NCT NCT00114231)

Last Updated: 2018-03-29

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

90 participants

Primary outcome timeframe

Up to 3 years

Results posted on

2018-03-29

Participant Flow

Participant milestones

Participant milestones
Measure	Original Dose Group 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.	Revised Dose Group 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.
Overall Study STARTED	62	28
Overall Study COMPLETED	53	26
Overall Study NOT COMPLETED	9	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Original Dose Group 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.	Revised Dose Group 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.
Overall Study No consent	2	0
Overall Study QARC requirement not met	1	0
Overall Study Suspected metastatic disease	1	0
Overall Study No adenocarcinoma	1	0
Overall Study Low creatinine clearance	0	1
Overall Study Tumor size > 4cm	1	0
Overall Study Tumor fixed on digital exam	0	1
Overall Study No Absolute Neutrophil Count	2	0
Overall Study Biopsy done after registration	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Original Dose Group n=53 Participants 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.	Revised Dose Group n=26 Participants 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 n=79 Participants Total of all reporting groups
Age, Continuous	62 years n=5 Participants	63 years n=7 Participants	62 years n=5 Participants
Sex: Female, Male Female	20 Participants n=5 Participants	6 Participants n=7 Participants	26 Participants n=5 Participants
Sex: Female, Male Male	33 Participants n=5 Participants	20 Participants n=7 Participants	53 Participants n=5 Participants
Region of Enrollment United States	53 Participants n=5 Participants	26 Participants n=7 Participants	79 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 3 years

Outcome measures

Outcome measures
Measure	Treatment (Capecitabine, Oxaliplatin, Radiotherapy, Surgery) n=79 Participants 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.
3-Year Disease-free Survival	88.2 percentage of patients Interval 81.3 to 95.8

SECONDARY outcome

Timeframe: At time of surgery

Population: Patients who had local excision are included in this analysis.

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

Outcome measures

Outcome measures
Measure	Treatment (Capecitabine, Oxaliplatin, Radiotherapy, Surgery) n=77 Participants 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.
R0 Resection Rate (Negative Margin Rate)	98.7 percentage of patients

SECONDARY outcome

Timeframe: Up to 30 days

Morbidity and mortality after neoadjuvant cheoradiotherapy and local excision.

Outcome measures

Outcome measures
Measure	Treatment (Capecitabine, Oxaliplatin, Radiotherapy, Surgery) n=79 Participants 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.
Morbidity and Mortality Rate Mortality	6 percentage of patients
Morbidity and Mortality Rate Morbidity	10 percentage of patients

SECONDARY outcome

Timeframe: Up to 5 years

Population: Patients assessable for pathology results were included in this analysis.

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.

Outcome measures

Outcome measures
Measure	Treatment (Capecitabine, Oxaliplatin, Radiotherapy, Surgery) n=77 Participants 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.
Rate of Pathologic Complete Response of the Primary Tumor	44 percentage of patients Interval 32.0 to 55.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Treatment (Capecitabine, Oxaliplatin, Radiotherapy, Surgery) n=79 Participants 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.
Local Recurrence Rate	4 percentage of patients

Adverse Events

Original Dose Group

Serious events: 6 serious events

Other events: 32 other events

Deaths: 0 deaths

Revised Dose Group

Serious events: 2 serious events

Other events: 25 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Original Dose Group n=57 participants at risk 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.	Revised Dose Group n=27 participants at risk 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.
Blood and lymphatic system disorders Hemoglobin decreased	0.00% 0/57 • Up to 3 years. 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.	3.7% 1/27 • Number of events 1 • Up to 3 years. 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.
Cardiac disorders Myocardial ischemia	1.8% 1/57 • Number of events 1 • Up to 3 years. 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.	0.00% 0/27 • Up to 3 years. 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.
General disorders Pain	1.8% 1/57 • Number of events 1 • Up to 3 years. 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.	0.00% 0/27 • Up to 3 years. 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.
Infections and infestations Appendicitis	1.8% 1/57 • Number of events 1 • Up to 3 years. 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.	0.00% 0/27 • Up to 3 years. 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.
Investigations Lymphocyte count decreased	1.8% 1/57 • Number of events 1 • Up to 3 years. 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.	0.00% 0/27 • Up to 3 years. 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.
Metabolism and nutrition disorders Dehydration	1.8% 1/57 • Number of events 1 • Up to 3 years. 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.	0.00% 0/27 • Up to 3 years. 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.
Metabolism and nutrition disorders Serum phosphate decreased	0.00% 0/57 • Up to 3 years. 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.	3.7% 1/27 • Number of events 1 • Up to 3 years. 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.
Metabolism and nutrition disorders Serum potassium decreased	1.8% 1/57 • Number of events 1 • Up to 3 years. 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.	0.00% 0/27 • Up to 3 years. 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.
Vascular disorders Hematoma	1.8% 1/57 • Number of events 1 • Up to 3 years. 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.	0.00% 0/27 • Up to 3 years. 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.

Other adverse events

Additional Information

Julio Garcia-Aguilar, MD

Memorial Sloan Kettering Cancer Center

Phone: 212-639-5506

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place