New treatment approach for high-risk rectal cancer using capecitabine and XELOX

Effect of Concurrent Capecitabine-based Long-term Radiotherapy Followed by 4 Cycles XELOX Pre- a Delayed TME Compared With 6 Cycles XELOX post-a Regular Timing TME in Patients With High Risk Rectal Cancer: a Multi-centers, Randomized, Open-Label Trial

This study is testing a new treatment plan using a combination of radiation and chemotherapy for people with high-risk rectal cancer to see if it helps them do better before surgery compared to the usual treatment.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 244 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Peking University People's Hospital (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 2 sites (Beijing, Beijing and 1 other locations)
• Trial ID: NCT03038256 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of concurrent capecitabine-based long-term radiotherapy followed by 4 cycles of XELOX chemotherapy before a delayed total mesorectal excision (TME) surgery, compared to the standard approach of 6 cycles of XELOX after TME. The study aims to improve local control and metastases-free survival rates in patients with high-risk rectal cancer, characterized by specific MRI findings. Participants will be randomly assigned to either the intervention or control group to assess the pathological response and overall outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with histologically confirmed adenocarcinoma of the rectum located 0-12 cm from the anal margin and classified as high-risk based on MRI findings.

Not a fit: Patients with metastatic disease, prior preoperative chemoradiotherapy, or other malignancies will not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to improved survival rates and better treatment outcomes for patients with high-risk rectal cancer.

How similar studies have performed: Other studies have shown promise with similar neoadjuvant approaches, but this specific combination is being evaluated for the first time.

Eligibility criteria

Inclusion Criteria:

1. Age of 18-75 years;
2. Histologically confirmed adenocarcinoma;
3. The rectal adenocarcinoma 0-12cm from the anal margin on Magnetic resonance imaging (MRI) and/or rigid sigmoidoscopy;
4. High risk of rectal cancer defined by high-resolution MRI: tumor invasion 5mm beyond the muscularis propria, or extramural vascular invasion, or circumferential resection margin unsafe, or the lower rectal cancer invades intersphincteric space, or rectal cancer invades the adjacent structures.
5. Eastern Collaborative Oncology Group performance status score of 0 or 2
6. Able and willing to give informed consent to participate.

Exclusion Criteria:

1. Received preoperative chemoradiotherapy for rectal cancer before the recruitment of this study;
2. Have metastatic disease (including non-regional lymph nodes metastases or resectable liver metastases);
3. Other malignancies, non-adenocarcinoma rectal malignancies or rectal malignancies on the basis of inflammatory bowel disease;
4. Emergency surgery due to bowel obstruction, perforation, bleeding, etc.;
5. Abnormality of capecitabine absorption due to gastrointestinal disease e.g. short bowel syndrome, inflammation bowel disease, et al.;
6. Unresectable concurrent intestinal lesions;
7. Concurrent severe infection；
8. Cardiac Disease：uncontrolled or symptomatic cardiac angina，or uncontrolled arrhythmias and hypertension, or severe congestive heart failure grade II or more based on New York Heart Association (NYHA); myocardial infarction within the past 12 months
9. Peripheral neuropathy more than grade 1 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE; version 3·0)
10. Bone marrow, liver and kidney function are abnormal e.g., white blood cell ≤ 1.5 × 109 / L; platelet ≤ 100 × 109 / L; Haemoglobin ≤ 80 g/L; Bilirubin \> 1.5 times the upper limit; aspartate aminotransferase and alanine aminotransferase \> 2.5 times the upper limit; creatinine \> 1.5 times the upper limit;
11. Pregnant or lactating women;
12. Life prediction less than 3 months, other severe diseases;
13. Contraindication to MRI; e.g. non-MRI compatible hip prosthesis, cardiac pacemaker;
14. Contraindication to standard chemotherapy including drug interactions and glomerular filtration rate \<50 mL/min at baseline;
15. Participators who had been recruited by other clinical trial within three months.

Where this trial is running

Beijing, Beijing and 1 other locations

• Peking University People's Hospital — Beijing, Beijing, China (Recruiting)
• Beijing Friendship Hospital — Beijing, Beijing, China (Not_yet_recruiting)

Study contacts

• Study coordinator: Yi Wang, MD, PHD

Conditions Rectal Cancer; Pathological Complete Response; Disease Free Survival; High Risk Rectal Cancer; Total neoadjuvant chemoradiotherapy; Lengthening interval between radiotherapy and surgery