Trial of Capecitabine With or Without Irinotecan Driven by UGT1A1

Study Overview
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Brief Summary
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The study evaluate the addition of Irinotecan in neoadjuvant chemoradiation. Half of participants will receive capecitabine alone together with neoadjuvant CRT, followed by a cycle of XELOX, while the other will receive capecitabine and irinotecan during CRT, followed by a cycle of XELIRI. All participants will be scheduled to receive surgery 6-8 weeks after the completion of CRT, then 5 cycles of adjuvant chemotherapy of XELOX.

Official Title
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A Randomized Phase III Trial of Capecitabine With or Without Irinotecan Driven by UGT1A1 in Neoadjuvant Chemoradiation of Locally Advanced Rectal Cancer

Conditions
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Locally Advanced Rectal Cancer

Intervention / Treatment
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* Radiation: Radiation
* Drug: Capecitabine
* Drug: Irinotecan
* Drug: Oxaliplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: pathological confirmed adenocarcinoma clinical stage T3-4 and/or N+ the distance from anal verge less than 12 cm without distance metastases KPS >=70 UGT1A1*28 6/6 or 6/7 without previous anti-cancer therapy sign the inform consent Exclusion Criteria: pregnancy or breast-feeding women serious medical illness baseline blood and biochemical indicators do not meet the following criteria: neutrophils≥1.5×10^9/L, Hb≥90g/L, PLT≥100×10^9/L, ALT/AST ≤2.5 ULN, Cr≤ 1 ULN DPD deficiency UGT1A1*28 7/7

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Capecitabine Alone<br>Concurrent Chemoradiotherapy: Radiation: 50Gy/25Fx; Capecitabine: 825mg/m2 bid Monday-Friday per week Chemotherapy in Interval Between CRT and Surgery: Capecitabine: 1000mg/m2 bid d1-14; Oxaliplatin: 130mg/m2 d1 Surgery: Scheduled 6-8 weeks after the completion of CRT Adjuvant Chemotherapy: Capecitabine: 1000mg/m2 bid d1-14; Oxaliplatin: 130mg/m2 d1; q3w, 5cycles | Radiation: Radiation<br>* Pelvic Radiation: 50Gy/25Fx<br>Drug: Capecitabine<br> <br> * Other names: Xeloda;Drug: Oxaliplatin<br> <br> |
| Experimental: Capecitabine with Irinotecan<br>Concurrent Chemoradiotherapy: Radiation: 50Gy/25Fx; Capecitabine: 625mg/m2 bid Monday-Friday per week; Irinotecan: 80mg/m2 (UGT1A1*28 6/6) or 65mg/m2 (UGT1A1*28 6/7) Chemotherapy in Interval Between CRT and Surgery: Capecitabine: 1000mg/m2 bid d1-14; Irinotecan: 200mg/m2 d1 Surgery: Scheduled 6-8 weeks after the completion of CRT Adjuvant Chemotherapy: Capecitabine: 1000mg/m2 bid d1-14; Oxaliplatin: 130mg/m2 d1; q3w, 5cycles | Radiation: Radiation<br>* Pelvic Radiation: 50Gy/25Fx<br>Drug: Capecitabine<br> <br> * Other names: Xeloda;Drug: Irinotecan<br> <br> * Other names: CPT-11;Drug: Oxaliplatin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologic Complete Response |  | Surgery scheduled 6-8 weeks after the end of chemoradiation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival |  | From date of randomization until the date of death from any cause, assessed up to 10 years | 
| Disease-free Survival |  | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 10 years | 
| Local Control rate | Number of participants with pelvic failure after surgery, evaluated using Kaplan-Meier Curve | From date of randomization until the date of first documented pelvic failure, assessed up to 10 years | 
| Number of participants with chemoradiation-related adverse events as assessed by CTCAE v4.0 |  | Up to 2 years | 
| Surgical complications |  | Surgery scheduled 6-8 weeks after the end of chemotherapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neoadjuvant Chemoradiation, Irinotecan, UGT1A1