Phase III Study of Neoadjuvant Chemotherapy With Capecitabine and Oxaliplatin Versus Chemoradiation for Locally Advanced Rectal Cancer Patients
Overview
- Phase
- Phase 3
- Intervention
- Oxaliplatin
- Conditions
- Rectal Neoplasms
- Sponsor
- Sun Yat-sen University
- Enrollment
- 663
- Locations
- 1
- Primary Endpoint
- Local-regional failure-free survival
- Status
- Active, not recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
Although neoadjuvant radiotherapy greatly decreases local recurrence in locally advanced rectal cancer patients undergoing surgery, it inevitably results in short-term and long-term toxicities. More importantly, it has not been confirmed that neoadjuvant radiotherapy could improve overall survival. The purpose of this study is to compare the effects of chemotherapy alone using a combination regimen known as XELOX (capecitabine and oxaliplatin ) and selective use of the standard treatment to the standard treatment of chemotherapy and radiation.
Detailed Description
This randomised, open-label, multicentre,phase 3 trial began in August, 2014, as an adjuvant trial comparing capecitabine-based neoadjuvant chemoradiotherapy with chemotherapy alone,in patients aged 18 years to 75 with clinical stage II-III locally advanced rectal cancer from six Chinese institutions. Patients with local advanced rectal cancer (T2N+ or T3-4aNany,M0, CRM≥2mm, 12cm from the anus verge) were scheduled to Group A: receive neoadjuvant chemotherapy alone (4 cycles of XELOX: oxaliplatin 130mg/m2 day 1，capecitabine 2000mg/m2 days 1-14, repeated every 21 days) followed by radical surgery and 4 cycles of XELOX ( oxaliplatin 130mg/m2 day 1，capecitabine 2000mg/m2 days 1-14, repeated every 21 days) and Group B :chemoradiotherapy (50.4 Gy plus capecitabine 1650 mg/m² administered orally and concurrently with radiation therapy for 5 days per week.) followed by radical surgery and 6 cycles of XELOX ( oxaliplatin 130mg/m2 day 1，capecitabine 2000mg/m2 days 1-14, repeated every 21 days) The primary endpoint was 3-year local recurrence free survival; analyses were done based on all patients with post-randomization data.
Investigators
Pei-Rong Ding
Associate Professor
Sun Yat-sen University
Eligibility Criteria
Inclusion Criteria
- •DISEASE CHARACTERISTICS:
- •Diagnosis of rectal adenocarcinoma
- •Radiologically measurable or clinically evaluable disease
- •Tumor location within 12cm from anal verge
- •Clinical stage T2N+ or T3-4aNany,M0 Clinical staging should be estimated based on the combination of the following assessments: physical examination by the primary surgeon, CT scan of the chest/abdomen/pelvis, and a pelvic MRI with or without an endorectal ultrasound (ERUS)
- •No evidence that tumor is adjacent to (defined as within 2 mm of) the mesorectal fascia on pre-operative MRI
- •No tumor causing symptomatic bowel obstruction
- •No distant metastasis
- •PATIENT CHARACTERISTICS:
- •ECOG performance status 0, 1
Exclusion Criteria
- •Pregnant or nursing
- •Patient of child-bearing potential is not willing to employ adequate contraception
- •Not willing to return to enrolling medical site for all study assessments
- •With other invasive malignancy ≤ 5 years prior to registration; exceptions are colonic polyps, non-melanoma skin cancer, or carcinoma-in-situ of the cervix
- •Chemotherapy within 5 years prior to registration (hormonal therapy is allowable if the disease-free interval is ≥ 5 years)
- •Prior pelvic radiation
Arms & Interventions
Chemotherapy
Patients receive neoadjuvant chemotherapy comprising oxaliplatin 130mg/m² ivdrip over 2 hours on day 1,capecitabine 2000 mg/m² on days 1-14, treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.Patients without disease progression undergo low-anterior resection (LAR) with total mesorectal excision (TME) and 4 cycles of XELOX ( oxaliplatin 130mg/m² day 1，capecitabine 2000mg/m² days 1-14, repeated every 21 days). Patients with disease progression undergo chemoradiation as in group chemoradiotherapy before proceeding to LAR with TME.
Intervention: Oxaliplatin
Chemotherapy
Patients receive neoadjuvant chemotherapy comprising oxaliplatin 130mg/m² ivdrip over 2 hours on day 1,capecitabine 2000 mg/m² on days 1-14, treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.Patients without disease progression undergo low-anterior resection (LAR) with total mesorectal excision (TME) and 4 cycles of XELOX ( oxaliplatin 130mg/m² day 1，capecitabine 2000mg/m² days 1-14, repeated every 21 days). Patients with disease progression undergo chemoradiation as in group chemoradiotherapy before proceeding to LAR with TME.
Intervention: capecitabine
Chemoradiotherapy
Patients receive capecitabine 825 mg/m² twice daily concurrently with radiation therapy for 5 days per week. Patients also undergo intensity-modulated radiation therapy 5 days a week for approximately 5.5 weeks. Patients then undergo LAR with TME and 4 cycles of XELOX ( oxaliplatin 130mg/m² day 1，capecitabine 2000mg/m² days 1-14, repeated every 21 days) .
Intervention: capecitabine
Chemoradiotherapy
Patients receive capecitabine 825 mg/m² twice daily concurrently with radiation therapy for 5 days per week. Patients also undergo intensity-modulated radiation therapy 5 days a week for approximately 5.5 weeks. Patients then undergo LAR with TME and 4 cycles of XELOX ( oxaliplatin 130mg/m² day 1，capecitabine 2000mg/m² days 1-14, repeated every 21 days) .
Intervention: Radiation
Outcomes
Primary Outcomes
Local-regional failure-free survival
Time Frame: Up to 5 years
the time interval between the date of randomization and the date of local or regional progression/relapse, or death, whichever occurred first.regional progression/relapse, or death, whichever occurred first.
Secondary Outcomes
- Disease free survival(Up to 5 years)
- Pathologic complete response and tumor regression grade(Up to 18 weeks)
- Pelvic R0 resection rate(Up to 18 weeks)
- Overall survival(Up to 5 years)
- Adverse event (AE) profiles(Up to 5 years)
- Rate of receiving pre-operative or post-operative chemoradiation(Up to 30 weeks)