Radiation-protection Effect of Amifostine in Locally Advanced Rectal Cancer

Study Overview
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Brief Summary
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The study evaluates the addition of Amifostine to capecitabine and irinotecan in neoadjuvant chemoradiation(CRT) in locally advanced rectal cancer. Half of participants will receive capecitabine and along with neoadjuvant radiotherapy, followed by a cycle of XELIRI, while the others will receive capecitabine and irinotecan added by amifostine 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 it will depends which regimens the patient would receive according to his or her pathological results.

Official Title
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A Phase II Trial of Capecitabine and Irinotecan With or Without Amifostine in Neoadjuvant Chemoradiotherapy in 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: Amifostine


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 performance status score: 0 1 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Capecitabine and Irinotecan without Amifostine<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: depends on patients pathological review. | Radiation: Radiation<br>* Pelvic Radiation: 50Gy/25Fx<br>Drug: Capecitabine<br>* 625mg/m2 bid Monday-Friday per week<br>* Other names: Xeloda;Drug: Irinotecan<br>* 80mg/m2 (UGT1A1*28 6/6) or 65mg/m2 (UGT1A1*28 6/7)<br>|
| Experimental: Capecitabine and Irinotecan with Amifostine<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) Amifostine: 400mg/m2 per week 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: depends on patients pathological review. | Radiation: Radiation<br>* Pelvic Radiation: 50Gy/25Fx<br>Drug: Capecitabine<br>* 625mg/m2 bid Monday-Friday per week<br>* Other names: Xeloda;Drug: Irinotecan<br>* 80mg/m2 (UGT1A1*28 6/6) or 65mg/m2 (UGT1A1*28 6/7)<br>Drug: Amifostine<br>* 400mg/m2 per week<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the morbidity of hematological adverse events and diarrhea as assessed by CTCAE v4.0 |  | during neoadjuvant chemoradiation. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of participants' quality of life during treatment as assessed by EQ-5D questionnaire and EORTC-QLQ-C30 questionnaire |  | during neoadjuvant chemoradiation. | 
| pathological response rate |  | Surgery scheduled 6-8 weeks after the end of chemoradiation. | 
| the morbidity of late radiation proctitis |  | late radiation proctitis is measured 9 months after the end of chemoradiation. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neoadjuvant Chemoradiotherapy, amifostine, irinotecan, capecitabine