Clinical Effect of Neoadjuvant Hierarchical Treatment Based on Chemotherapy

Clinical Effect of Neoadjuvant Hierarchical Treatment Based on Chemotherapy for T3-4N0-2M0 Middle and Lower Rectal Cancer

Clinical effect of neoadjuvant hierarchical treatment based on chemotherapy for T3-4N0-2M0 middle and lower rectal cancer

Study Overview

• Status: Unknown
• Conditions: Rectum Cancer
• Intervention / Treatment: Procedure: TME; Drug: neoadjuvant CT; Drug: adjuvant CT; Radiation: Concurrent chemo-radiotherapy

Detailed Description

By setting 3-Year disease-free survival (DFS) as main objective, the treatment strategy will be optimizing as neoadjuvant chemotherapy alone and chemo-radio-chemo sequential treatment.

• Study Type: Interventional
• Enrollment (Anticipated): 1
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: binbin Cui, Doctor; Phone Number: +86-13351112888; Email: Cuibb2017@163.com
• Study Contact Backup: Name: yanlong Liu, Doctor; Phone Number: +86-13845082914; Email: liuyanlong1979@163.com

Study Locations

• China
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150000
      • Recruiting
      • Cancer Hospital Affiliated to Harbin Medical University
      • Contact: binbin cui

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

• Inclusion criteria
• Pathologically confirmed to be rectal adenocarcinoma.
• Distance < 10cm from the end of the tumor to the anal verge found on colonoscopy
• Tumor in stage T3-4N0-2 (pelvic MRI evaluation)
• Patients without distant metastases (such as liver and peritoneum, lungs, aortic lymph nodes)
• Patients with Karnofsky score greater ≥ 70
• WBC > 3.5 x 109/ml , PLT > 10 x 109/ml , TBIL<22.2 umol/l , BUN <7.14mmol/l , Cr<132umol/l or Ccr > 50ml/min (Evaluated using the Cockcroft-Gault formula: Creatinine clearance (male) = {(140 - age) x LBM (kg)} / {plasma creatinine (mg/dl) x 72} ; Creatinine clearance (female) = 0.85 x {(140 - age) x LBM(kg)}/ { plasma creatinine (mg/dl) x 72})
• Patients must sign the informed consent form
• Female subjects must be contraceptive during the trial
• Patients who did not receive any form of chemotherapy and radiotherapy
• No other important related diseases (such as other tumors, severe heart disease and central nervous system diseases, etc.)
• Age must be equal or more than 20 and must be equal or less than 70
• Exclusion criteria
• Previously received radiation therapy, chemotherapy or anti-tumor biological therapy
• Previously received immuno-suppressive therapy
• Participation in interventional clinical trial over the past time
• Suffering from malignant colonic neoplasms simultaneously
• With peripheral neuropathy(above WHO I level)
• Affected cognitive abilities because of neurological or psychiatric abnormalities Including central nervous system metastasis
• Medical history of severe allergies or allergic constitution
• Severe pulmonary or heart disease history
• Female patients who are in pregnancy or lactation and refuse contraception
• Previously with other malignant tumors
• Exit criteria
• Occurrence of bleeding, obstruction, perforation and other complications
• Occurrence of distant metastasis during the period of neoadjuvant therapy
• Adverse reactions, not be tolerated and do not want to continue to receive treatment
• Patients voluntarily quit
• Capecitabine-related Grade 4 Hand-Foot Syndrome

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Preoperative neoadjuvant CT; Give neoadjuvant chemotherapy for four cycle ,if achieve cCR or cPR after four cycles neoadjuvant chemotherapy , receive Total Mesorectal Excision(TME) ,then received the complete adjuvant therapy	Procedure: TME; Find the hypogastric nerve trunk in front of sacral promontory and protect it,be careful to use electrocautery hemostasis biased toward the side of rectal when handle lateral ligament of rectum and middle rectal artery and avoid to damage the pelvic plexus.; At least a 2-cm margin to the lower edge of the tumor is adequate for distal bowel resection. Resect 5cm length distal rectal or all of the mesorectum.Check the integrity of the mesorectum in postoperative routine examination. Double stapling method is used for all low anastomosis operations.; Drug: neoadjuvant CT; CAPEOX protocol:Oxaliplatin 130mg/m2 ivgtt 2-6h dl;(Capecitabine 1000mg/m2 2 times a day lasts for 14 days Repeat every 3 weeks; Other Names: neoadjuvant chemotherapy; Drug: adjuvant CT; CAPEOX protocol:Oxaliplatin 130mg/m2 ivgtt 2-6h dl;(Capecitabine 1000mg/m2 2 times a day lasts for 14 days Repeat every 3 weeks; Other Names: adjuvant chemotherapy
Experimental: Preoperative neoadjuvant CT-RCT; Give neoadjuvant chemotherapy for four cycle ,if not achieve cCR or cPR after four cycle neoadjuvant chemotherapy ,give concurrent chemo-radiotherapy,then additional neoadjuvant chemotherapy for 2 cycles ,then receive Total Mesorectal Excision(TME) ,then received the complete adjuvant therapy	Procedure: TME; Find the hypogastric nerve trunk in front of sacral promontory and protect it,be careful to use electrocautery hemostasis biased toward the side of rectal when handle lateral ligament of rectum and middle rectal artery and avoid to damage the pelvic plexus.; At least a 2-cm margin to the lower edge of the tumor is adequate for distal bowel resection. Resect 5cm length distal rectal or all of the mesorectum.Check the integrity of the mesorectum in postoperative routine examination. Double stapling method is used for all low anastomosis operations.; Drug: neoadjuvant CT; CAPEOX protocol:Oxaliplatin 130mg/m2 ivgtt 2-6h dl;(Capecitabine 1000mg/m2 2 times a day lasts for 14 days Repeat every 3 weeks; Other Names: neoadjuvant chemotherapy; Drug: adjuvant CT; CAPEOX protocol:Oxaliplatin 130mg/m2 ivgtt 2-6h dl;(Capecitabine 1000mg/m2 2 times a day lasts for 14 days Repeat every 3 weeks; Other Names: adjuvant chemotherapy; Radiation: Concurrent chemo-radiotherapy; Three-dimensional conformal radiotherapy as following: CTV 44Gy/22 times＋GTV1 6Gy/3 times(2Gy/time/day，5 days a week，totally 5 weeks),if rectal tumors do not regress obviously, additional GTV2 is necessary, 5.4Gy/3 times (1.8Gy/time/day). At the same time, Capecitabine (850mg/m2, two times every day) will be taken on radiotherapy day; Other Names: neoadjuvant RCT
Active Comparator: Concurrent chemo-radiotherapy; Give concurrent chemo-radiotherapy ,then receive Total Mesorectal Excision(TME) ,then received the complete adjuvant therapy	Procedure: TME; Find the hypogastric nerve trunk in front of sacral promontory and protect it,be careful to use electrocautery hemostasis biased toward the side of rectal when handle lateral ligament of rectum and middle rectal artery and avoid to damage the pelvic plexus.; At least a 2-cm margin to the lower edge of the tumor is adequate for distal bowel resection. Resect 5cm length distal rectal or all of the mesorectum.Check the integrity of the mesorectum in postoperative routine examination. Double stapling method is used for all low anastomosis operations.; Drug: adjuvant CT; CAPEOX protocol:Oxaliplatin 130mg/m2 ivgtt 2-6h dl;(Capecitabine 1000mg/m2 2 times a day lasts for 14 days Repeat every 3 weeks; Other Names: adjuvant chemotherapy; Radiation: Concurrent chemo-radiotherapy; Three-dimensional conformal radiotherapy as following: CTV 44Gy/22 times＋GTV1 6Gy/3 times(2Gy/time/day，5 days a week，totally 5 weeks),if rectal tumors do not regress obviously, additional GTV2 is necessary, 5.4Gy/3 times (1.8Gy/time/day). At the same time, Capecitabine (850mg/m2, two times every day) will be taken on radiotherapy day; Other Names: neoadjuvant RCT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Free Survival (DFS)	the treatment strategy will be optimizing as neoadjuvant chemotherapy alone and chemo-radio-chemo sequential treatment.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Surgery related mortality and complication	Surgery related mortality and complication	3 years
Resection rate of R0	Resection rate of R0	3 years
Pathologic complete remission (pCR) rate	Pathologic complete remission (pCR) rate	3 years
Tolerance after neoadjuvant treatment	Tolerance after neoadjuvant treatment	3 years
Predictor efficacy of neoadjuvant chemotherapy for DFS	Predictor efficacy of neoadjuvant chemotherapy for DFS	3 years

Collaborators and Investigators

• Sponsor: Harbin Medical University
• Investigators: Principal Investigator: binbin cui, Harbin Medical University

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2017
• Primary Completion (Anticipated): September 30, 2018
• Study Completion (Anticipated): September 30, 2021

Study Registration Dates

• First Submitted: February 26, 2017
• First Submitted That Met QC Criteria: March 3, 2017
• First Posted (Actual): March 6, 2017

Study Record Updates

• Last Update Posted (Actual): March 7, 2017
• Last Update Submitted That Met QC Criteria: March 6, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Neoadjuvant Chemotherapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms
• Other Study ID Numbers: 201702230001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No