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

NCT ID: NCT03975049

Last Updated: 2019-06-05

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 933 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-31
• Study Completion Date: 2029-07-31

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.

Conditions

Rectal Cancer; Chemotherapy Effect

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

5-Fu + RT

5Fu + RT for five weeks --- 6-8 weeks of interval --- TME --- mFOLFOX \* 6-8

Group Type: ACTIVE_COMPARATOR

Chemoradiation

Intervention Type: RADIATION

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

mFOLFOXIRI

mFOLFOXIRI \* 4 --- TME --- mFOLFOXIRI \* 4

Group Type: EXPERIMENTAL

FOLFOXIRI Protocol

Intervention Type: DRUG

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.

mFOLFOX

mFOLFOX \* 9 --- TME --- mFOLFOX \* 3

Group Type: EXPERIMENTAL

Folfox Protocol

Intervention Type: DRUG

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.

Interventions

Chemoradiation

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

Intervention Type: RADIATION

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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sixth Affiliated Hospital, Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ping Lan, MD

Role: PRINCIPAL_INVESTIGATOR

Sixth Affiliated Hospital, Sun Yat-sen University

Central Contacts

Ping Lan, MD

Role: CONTACT

lanping@mail.sysu.edu.cn

86-20-38285497

Jian Xiao, MD

Role: CONTACT

xiaoj26@mail.sysu.edu.cn

86-20-38285497

Other Identifiers

SAHMO201

Identifier Type: -

Identifier Source: org_study_id