A Study of Chinese Herbal Compound Dendrobium Huoshanense Granules in NCRT for Patients With Locally Advanced Rectal Cancer

Study Overview
=================
Brief Summary
-----------------
The study evaluates the addition of Chinese Herbal Compound Dendrobium Huoshanense Granules to capecitabine and irinotecan in neoadjuvant chemoradiation(CRT) in locally advanced rectal cancer. Half of participants will receive CRT with Dendrobium Huoshanense Granules, while the others will receive CRT with placebo. We will evaluate whether Dendrobium Huoshanense Granules can enhance the immune function and alleviate symptoms caused by the tumor and CRT .

Official Title
-----------------
A Phase II Randomized Study of the Protection Effect of Chinese Herbal Compound Dendrobium Huoshanense Granules in NCRT for Patients With Locally Advanced Rectal Cancer

Conditions
-----------------
Locally Advanced Rectal Cancer

Intervention / Treatment
-----------------
* Drug: Dendrobium Huoshanense Granules
* Radiation: Pelvic Radiation
* Drug: Capecitabine
* Drug: Irinotecan
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: pathological confirmed rectum adenocarcinoma clinical stage T3-4 and/or N+ the distance from anal verge less than 10 cm without distance metastases performance status score: 0 1 UGT1A1*28 6/6 or 6/7 without previous anti-cancer therapy able to follow the protocol during the study period sign the inform consent Exclusion Criteria: Pregnant or breastfeeding women Those with other history of malignant disease in the past 5 years, except for cured skin cancer and cervical carcinoma in situ If there is an uncontrolled history of epilepsy, central nervous system disease or mental disorder, the investigator may determine that the clinical severity may hinder the signing of informed consent or affect the patient's oral medication compliance. Clinically severe (ie, active) heart disease, such as symptomatic coronary heart disease, New York Heart Association (NYHA) class II or more severe congestive heart failure or severe arrhythmia requiring medication intervention (see appendix 12), or a history of myocardial infarction in the last 12 months Organ transplantation requires immunosuppressive therapy Severe uncontrolled recurrent infections, or other serious uncontrolled concomitant diseases Subject blood routine and biochemical indicators do not meet the following criteria: hemoglobin ≥ 90g / L; absolute neutrophil count (ANC) ≥ 1.5 × 109 / L; Alanine transaminase (ALT), aspartate aminotransferase (AST) ≤ 2.5 times the upper limit of normal; alkaline phosphatase (ALP) ≤2.5 times the normal upper limit; serum total bilirubin <1.5 times the normal upper limit; serum creatinine <1 times the normal upper limit; serum albumin ≥ 30g / L Anyone who is allergic to any research medication DPD deficiency UGT1A1*28 7/7

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CRT with Dendrobium Huoshanense<br>Dendrobium Huoshanense Granules: 3g tid per day for 5weeks 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. | Drug: Dendrobium Huoshanense Granules<br>* 3g tid per day for 5weeks<br>Radiation: Pelvic Radiation<br>* 50Gy/25Fx<br>Drug: Capecitabine<br>* 625mg/m2 bid Monday-Friday per week<br>Drug: Irinotecan<br>* 80mg/m2 (UGT1A1*28 6/6) or 65mg/m2 (UGT1A1*28 6/7)<br>|
| Placebo Comparator: CRT with Placebo<br>Placebo: 3g tid per day for 5weeks 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: Pelvic Radiation<br>* 50Gy/25Fx<br>Drug: Capecitabine<br>* 625mg/m2 bid Monday-Friday per week<br>Drug: Irinotecan<br>* 80mg/m2 (UGT1A1*28 6/6) or 65mg/m2 (UGT1A1*28 6/7)<br>Other: Placebo<br>* 3g tid per day for 5weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the morbidity of hematological adverse events and diarrhea as assessed by CTCAE v4.0 |  | twice weekly during the neoadjuvant chemotherapy (5 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of participants' quality of life during treatment as assessed by EQ-5D questionnaire |  | once weekly during the neoadjuvant chemotherapy (5 weeks) | 
| Impact of participants' quality of life during treatment as assessed by EORTC-QLQ-C30 questionnaire |  | once weekly during the neoadjuvant chemotherapy (5 weeks) | 
| ORR(objective response rate) includes CR(complete rate) and PR(partial rate) |  | Surgery scheduled 6-8 weeks after the end of chemoradiation | 
| Number of the concurrent chemotherapy cycles that patients can receive during radiotherapy |  | once weekly during neoadjuvant chemoradiation(5 weeks,each cycle is one week) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Neoadjuvant Chemoradiotherapy, Dendrobium Huoshanense, irinotecan, capecitabine