Comparing two chemotherapy approaches for advanced rectal cancer before surgery

Prospectively Randomized Control Clinical Trial of FOLFOXIRI Preoperative Chemotherapy Alone on Rectal Cancer in Local Advance Comparing to Oral Capecitabine Combined With Long-term Radiation

This study is testing whether a new three-drug chemotherapy treatment can help people with advanced rectal cancer do better before surgery compared to the standard treatment.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 776 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Sun Yat-sen University (other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 2 sites (Guangzhou, Guangdong and 1 other locations)
• Trial ID: NCT03671252 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effectiveness and safety of a three-drug chemotherapy regimen known as FOLFOXIRI compared to standard treatment with capecitabine combined with radiotherapy for patients with locally advanced rectal cancer. It is a multicenter, randomized phase III study where patients will be stratified based on the distance of their tumor from the anal margin and will receive either treatment while receiving full supportive care. The primary objective is to assess the three-year disease-free survival rate, while secondary objectives include evaluating local recurrence rates, overall survival, surgical complications, and long-term quality of life.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 to 75 with a histological diagnosis of rectal adenocarcinoma and specific tumor characteristics that allow for R0 resection.

Not a fit: Patients with distant metastasis or those whose tumors do not meet the specified criteria for R0 resection may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a more effective preoperative treatment option for patients with locally advanced rectal cancer, potentially improving survival rates and quality of life.

How similar studies have performed: Other studies have explored similar chemotherapy regimens, but the specific combination of FOLFOXIRI in this context is relatively novel.

Eligibility criteria

Inclusion Criteria:

* 1）Age: 18 to 75 years old;
* 2）Histological diagnosis of rectal adenocarcinoma;
* 3）Distance form anal margin ≤ 5cm: cT3-4aN + M0, there is no distant metastasis, lymph node positive, or the tumor breaking through the muscular layer, no invasion of the adjacent organs , positive MRF, it is estimated that R0 resection can be performed;
* 4）From the anal margin\>5cm: cT3c-4aN+M0, there is no distant metastasis, lymph node positive, or the tumor breaking through the muscular layer with invading the mesorectum more than 5mm, no invasion of the adjacent organs, positive MRF, it is estimated that R0 resection can be performed;
* 5）Preoperative staging method: All patients undergoing anal examination, high-resolution MRI and/or EUS for preoperative staging. The diameter of parenteral lymph node ≥10mm, lymph node shape or the MRI characteristics is consistent with typical lymph node metastasis. If combined with EUS, the material should be submitted to the central assessment team for judgment when there is a contradiction in the staging method. Preoperative chest and abdomen CT, pelvic MRI are used for excluding distant metastasis;
* 6）Confirmed as the lower edge of tumor is located within 12 cm from the anal margin by MRI examination
* 7）There is no signs of intestinal obstruction, or obstruction of intestinal after treating with proximal colostomy has been relieved;
* 8）Patients did not previously receive rectal surgery, chemotherapy or radiation therapy , biological treatment , except for endocrine therapy;
* 9）ECOG Performance Status :0-1
* 10）Life expectancy: more than 2 years;
* 11）Laboratory values：Hematology: white blood cell count\>4000/mm3; Platelet count\>100000/mm3; Hemoglobin \>10g/dL; Liver function: SGOT and SGPT \< 1.5 upper limit of normal(ULN); Bilirubin\< 1.5mg/dL; Renal function :Creatinine \<1.8mg/dL.

Exclusion Criteria:

* 1）Tumor invasion of surrounding tissue organs (T4b) by preoperative staging assessment;
* 2）Obturator lymph node metastasis;
* 3）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;
* 4）Severe hypertension with poor control;
* 5）History of HIV infection or active phase of chronic hepatitis B or C infection with high copy viral DNA;
* 6）Other active serious infections according to NCI-CTC version 4.0;
* 7）There is preoperative evidence for distant metastasis outside pelvis;
* 8）Cachexia and organ function decompensation
* 9）History of pelvic or abdominal radiotherapy;
* 10）Multiple primary cancer;
* 11）Patients with epilepcy requiring treatment ( steroids or antiepileptic treatment);
* 12）History of other malignant tumors within 5 years, except for cured cervical carcinoma in situ or skin basal cell carcinoma;
* 13）Drug abuse and medical, psychological or social conditions interfering patient participation in research or the evaluation of research results;
* 14）Any allergy to clinical research drugs or any drugs associated with this study;
* 15）Any unstable condition or condition that may endanger safety and compliance of patients;
* 16）Pregnancy or the lactating female without adequate contraception.

Where this trial is running

Guangzhou, Guangdong and 1 other locations

• Cancer center of Sun Yat-sen University — Guangzhou, Guangdong, China (RECRUITING)
• Medical Oncology,Sun Yat-sen University Cancer Center — Guangzhou, Guangdong, China (NOT_YET_RECRUITING)

Study contacts

• Principal investigator: Rui-hua Xu — Sun Yat-sen University
• Study coordinator: ZhiZhong Pan

Conditions: Rectal Cancer