Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Triplet Combination or Doublet Regimen Versus Chemoradiation as Neoadjuvant Therapy for Locally Advanced Rectal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03975049
Recruitment Status : Not yet recruiting
First Posted : June 5, 2019
Last Update Posted : June 5, 2019
Sponsor:
Information provided by (Responsible Party):
Sixth Affiliated Hospital, Sun Yat-sen University

Tracking Information
First Submitted Date  ICMJE May 22, 2019
First Posted Date  ICMJE June 5, 2019
Last Update Posted Date June 5, 2019
Estimated Study Start Date  ICMJE August 2019
Estimated Primary Completion Date July 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 2, 2019)
Disease-free survival [ Time Frame: 3 years ]
The interval from randomization to local recurrence, distant metastasis, death or the last follow-up.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: June 2, 2019)
  • Recurrence-free survival [ Time Frame: 3 years ]
    The interval from randomization to local recurrence, death or the last follow-up.
  • Metastasis-free survival [ Time Frame: 3 years ]
    The interval from randomization to distant metastasis, death or the last follow-up.
  • Surgical complication [ Time Frame: 3 years ]
    Surgical complication including anastomotic leakage, anastomotic stricture, intestinal obstruction, postoperative pelvic bleeding and poor wound healing.
  • Treatment related quality of life [ Time Frame: up to 3 years ]
    EORTC QOL questionaire
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: June 2, 2019)
Tumor regression grade after neoadjuvant therapy [ Time Frame: 3 months ]
According to pathological slides
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Triplet Combination or Doublet Regimen Versus Chemoradiation as Neoadjuvant Therapy for Locally Advanced Rectal Cancer
Official Title  ICMJE A Prospectively Randomized Phase III Trial Comparing Short-term mFOLFOXIRI, Long-term mFOLFOX6 and Traditional Chemoradiation as Preoperative Neoadjuvant Therapy for Locally Advanced Rectal Cancer
Brief Summary

Preoperative radiation with single agent chemotherapy as sensitizer is the standard care of locally advanced rectal cancer.

Local irradiation significantly increases surgical complications and impairs quality of life.

Combination chemotherapy alone seems promising and provides similar benefit to chemoradiation as neoadjuvant therapy.

Early administration of systemic therapy is also proved beneficial for long-term survival.

The purpose of this study is to compare the efficacy of chemotherapy alone with short-term modified FOLFOXIRI or long-term mFOLFOX with standard chemoradiation as neoadjuvant therapy for locally advanced rectal cancer.

Detailed Description

Patients with cT3-4 or cN+ and cM0 by pelvic MR and chest + abdominal CT scan will be randomized to the following three groups:

Group A: Traditional chemoradiation.

Fluorouracil 225 mg/m2/day continuous intravenous infusion on weekdays for five weeks; local irradiation 2GY/day on weekdays, totally 50GY.

At the end of chemoradiation, patients will receive an evaluation with MR and CT scan.

If the efficacy is defined as CR, PR or SD, the TME will be performed in 6-8 weeks since the last irradiation.

If the disease progress with the possibility of R0 resection, the operation will be given soon.

If the tumor progress to impossible for R0 resection, the salvage chemotherapy will be given accordingly.

Adjuvant chemotherapy of 6-8 cycles of mFOLFOX will be administered 3-4 weeks after R0 resection.

Group B: Short-term mFOLFOXIRI.

Oxaliplatin 85 mg/m2 on day 1; irinotecan 150 mg/m2 on day 1; leucovorin 400 mg/m2 on day 1; fluorouracil 2400 mg/m2 civ over 46h; treatment will be repeated every 14 days; prophylactic G-CSF support is recommended.

Patients are planned to receive 4 cycles of mFOLFOXIRI regimen preoperatively and postoperatively, respectively.

Before operation, efficacy evaluations will be performed every two cycles by CT and MR scan.

If the evaluation is defined as no progression without severe toxicity, the next 2 cycles will be given.

If the primary lesion progress without distant metastasis, patients will be assigned to group A.

If distant metastasis occurr during chemotherapy, patients will withdraw from the trial and be treated further at the discretion of attending physicians.

Postoperative chemotherapy will initiate 3-4 weeks after R0 resection.

Group C: Long-term mFOLFOX.

Oxaliplatin 85 mg/m2 on day 1; leucovorin 400 mg/m2 on day 1; fluorouracil 400 mg/m2 bolus and 2400 mg/m2 civ over 46h; treatment will be repeated every 14 days.

Patients are planned to receive 8-9 cycles of mFOLFOX regimen preoperatively and 3-4 cycles postoperatively.

Efficacy evaluations will be performed every three cycles by CT and MR scan before TME.

If the evaluation is defined as no progression without severe toxicity, the next 3 cycles of mFOLFOX will be given with the maximum of 9 cyces.

If the primary lesion progress without distant metastasis, patients will be assigned to group A.

If distant metastasis occurr during chemotherapy, patients will withdraw from the trial and be treated further at the discretion of attending physicians.

Postoperative chemotherapy will initiate 3-4 weeks after R0 resection.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Rectal Cancer
  • Chemotherapy Effect
Intervention  ICMJE
  • Radiation: Chemoradiation
    Fluorouracil 225 mg/m2/day continuous intravenous infusion on weekdays for five weeks; local irradiation 2GY/day on weekdays, totally 50GY.
  • Drug: FOLFOXIRI Protocol
    Oxaliplatin 85 mg/m2 on day 1; irinotecan 150 mg/m2 on day 1; leucovorin 400 mg/m2 on day 1; fluorouracil 2400 mg/m2 civ over 46h; treatment will be repeated every 14 days; prophylactic G-CSF support is recommended.
  • Drug: Folfox Protocol
    Oxaliplatin 85 mg/m2 on day 1; leucovorin 400 mg/m2 on day 1; fluorouracil 400 mg/m2 bolus and 2400 mg/m2 civ over 46h; treatment will be repeated every 14 days.
Study Arms  ICMJE
  • Active Comparator: 5-Fu + RT
    5Fu + RT for five weeks --- 6-8 weeks of interval --- TME --- mFOLFOX * 6-8
    Intervention: Radiation: Chemoradiation
  • Experimental: mFOLFOXIRI
    mFOLFOXIRI * 4 --- TME --- mFOLFOXIRI * 4
    Intervention: Drug: FOLFOXIRI Protocol
  • Experimental: mFOLFOX
    mFOLFOX * 9 --- TME --- mFOLFOX * 3
    Intervention: Drug: Folfox Protocol
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: June 2, 2019)
933
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2029
Estimated Primary Completion Date July 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 1)Age: 18 to 75 years old;
  • 2)Histological diagnosis of rectal adenocarcinoma;
  • 3)Distance form anal margin ≤ 12cm: cT3-4 or cN+ and cM0 by pelvic MR and chest + abdominal CT, estimated possible for R0 resection;
  • 4)There is no signs of intestinal obstruction, or obstruction of intestinal after treating with proximal colostomy has been relieved;
  • 5)Patients did not previously receive rectal surgery, chemotherapy or radiation therapy , biological treatment , except for endocrine therapy;
  • 6)ECOG Performance Status :0-1
  • 7)Life expectancy: more than 3 years;
  • 8)sufficient bone marrow, liver and kidney function.

Exclusion Criteria:

  • 1)Arrhythmia requires treatment with antiarrhythmia (except for beta-blockers or digoxin), symptomatic coronary artery disease, myocardial ischemia (myocardial infarction within the last 6 months) or congestive heart failure exceeding NYHA class II;
  • 2)Severe hypertension with poor control;
  • 3)History of HIV infection or active phase of chronic hepatitis B or C infection with high copy viral DNA;
  • 4)Other active serious infections according to NCI-CTC version 4.0;
  • 5)There is preoperative evidence for distant metastasis outside pelvis;
  • 6)Cachexia and organ function decompensation
  • 7)History of pelvic or abdominal radiotherapy;
  • 8)Multiple primary cancer;
  • 9)Patients with epilepcy requiring treatment ( steroids or antiepileptic treatment);
  • 10)History of other malignant tumors within 5 years, except for cured cervical carcinoma in situ or skin basal cell carcinoma;
  • 11)Drug abuse and medical, psychological or social conditions interfering patient participation in research or the evaluation of research results;
  • 12)Any allergy to clinical research drugs or any drugs associated with this study;
  • 13)Any unstable condition or condition that may endanger safety and compliance of patients;
  • 14)Pregnancy or the lactating female without adequate contraception.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Ping Lan, MD 86-20-38285497 lanping@mail.sysu.edu.cn
Contact: Jian Xiao, MD 86-20-38285497 xiaoj26@mail.sysu.edu.cn
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03975049
Other Study ID Numbers  ICMJE SAHMO201
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Sixth Affiliated Hospital, Sun Yat-sen University
Study Sponsor  ICMJE Sixth Affiliated Hospital, Sun Yat-sen University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Ping Lan, MD Sixth Affiliated Hospital, Sun Yat-sen University
PRS Account Sixth Affiliated Hospital, Sun Yat-sen University
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP