Chemotherapy Combined With High-dose Radiotherapy for Low Rectal Cancer Using MR Guided Linear Accelerator

• Conditions: Rectal Cancer
• Interventions: Radiation: Magnetic resonance guided radiotherapy; Drug: Chemotherapy

• Registration Number: NCT05338866
• Lead Sponsor: Sun Yat-sen University

Brief Summary

The incidence rate of colorectal cancer is third in male tumors and second in female tumors. The newly diagnosed incidence of colorectal cancer is no less than 100 thousand in China, which poses a great threat to people's health and a heavy burden of public health. Preoperative neoadjuvant radiotherapy and chemotherapy combined with radical surgery is recommended for locally advanced rectal cancer. Low rectal cancer accounts for about one third of all rectal cancer cases. Due to the particularity of its location，surgical complications and postoperative patients need permanent colostomy (artificial anus) to solve the defecation problems, which has a serious impact on the patients' work and life. How to improve the quality of life of patients without reducing the survival rate has become an important topic in the treatment of low rectal cancer. Previous studies have shown that the prognosis of patients with pathological complete remission (pCR) after neoadjuvant chemoradiotherapy for rectal cancer is optimistic. The clinical efficacy of "observation and waiting" is good. The results of small sample exploratory clinical studies of radical radiotherapy and chemotherapy for low rectal cancer are satisfactory, and MR-linear accelerator can be used for precision radiotherapy for colorectal cancer.

This study is aimed to explore the efficacy and safety of radical radiotherapy boost for low rectal cancer by using magnetic resonance guided radiotherapy system, and further evaluate the impact of boost on the quality of life of patients.

Detailed Description

It is a prospective phase II, non-randomized controlled designed clinical study. For the optimal design, 58 cases of low rectal adenocarcinoma without metastasis were divided into queue 1 and queue 2 according to the start time of boost. MR-linear accelerator was used for dose boost of the local tumor region to make it reaching the radical radiotherapy dose. At the same time, fluorouracil based chemotherapy was given according to stages.

The primary endpoint was 3-year progression free survival rate. The secondary end points were 3-year stoma free survival rate, 3-year local regeneration rate, 3-year disease-free survival rate, 3-year distant metastasis rate, 3-year overall survival rate, short term and long-term toxic and side effects, and patients' quality of life scale 1-3 years after treatment.

Study Timeline

• Study Start: 2022-01-01
• Study First Submitted: 2022-04-05
• Study First Submitted QC: 2022-04-14
• Study First Posted: 2022-04-21
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-21
• Last Update Posted: 2023-11-22
• Primary Completion: 2030-12-31
• Study Completion: 2033-12-31

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 58

Inclusion Criteria

1. Histologically confirmed as rectal adenocarcinoma.
2. MRI and / or electronic colonoscopy confirmed that the lower edge of the tumor was ≤ 5cm from the anal edge.
3. The AJCC clinical stage was cT1-4NxM0, with or without MRF positive and EMVI positive.
4. MSI gene detection or MMR protein immunohistochemical detection was MSS / PMMR.
5. No obvious signs of intestinal obstruction or intestinal obstruction has been relieved after proximal colostomy.
6. Age: 18 ~ 80 years old.
7. ECOG score: 0-1.
8. Expected life: more than 3 years.
9. Hematology: WBC > 3 × 109/L; PLT>80 × 109/L; Hb>90g/L.
10. Liver function: ALT and AST were less than 2 times of normal value; Bilirubin is less than 1.5 times of normal value.
11. Renal function: creatinine is less than 1.5 times of normal value or creatinine clearance rate (CCR) ≥ 60ml / min.
12. Patient who has not received tumor resection, radiotherapy, chemotherapy, immunotherapy or other anti-tumor treatment.

Exclusion Criteria

1. There are any conditions that make MRI impossible.
2. There are serious medical complications.
3. Uncontrolled infectious diseases, autoimmune diseases and mental diseases.
4. Any unstable condition or situation that may endanger patient safety and compliance.
5. Pregnant or lactating women who are fertile and do not take adequate contraceptive measures.
6. Refuse to sign informed consent.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Cohort 1. Cohort 2	Magnetic resonance guided radiotherapy	A total of 6 courses of oxaliplatin plus capecitabine chemotherapy and 2 courses of capecitabine single drug chemotherapy were performed. Concurrent chemoradiotherapy starts at the second cycle. Cohort 1: For patients with low rectal cancer who refused surgery before the initial diagnosis and treatment, the first stage of radiotherapy used conventional linear accelerated radiotherapy, with doses of GTV 50Gy/25f and CTV 45Gy/25f for 5-6 weeks. Subsequently, the second stage of radiotherapy boost was continued with MR linear accelerator, and the dose was GTV 16\~20Gy/8\~10f for 2 weeks. Cohort 2: For locally advanced low rectal cancer patients who did not achieve clinical complete remission 6-8 weeks after neoadjuvant radiochemotherapy and refused surgery, radiotherapy was given in the first stage at the doses of GTV 50Gy/25f and CTV 45Gy/25f for 5-6 weeks. In the second stage, MR linear accelerator was used for radiotherapy boosting, and the dose was GTV 30Gy/15f for 3 weeks.
Cohort 1. Cohort 2	Chemotherapy	A total of 6 courses of oxaliplatin plus capecitabine chemotherapy and 2 courses of capecitabine single drug chemotherapy were performed. Concurrent chemoradiotherapy starts at the second cycle. Cohort 1: For patients with low rectal cancer who refused surgery before the initial diagnosis and treatment, the first stage of radiotherapy used conventional linear accelerated radiotherapy, with doses of GTV 50Gy/25f and CTV 45Gy/25f for 5-6 weeks. Subsequently, the second stage of radiotherapy boost was continued with MR linear accelerator, and the dose was GTV 16\~20Gy/8\~10f for 2 weeks. Cohort 2: For locally advanced low rectal cancer patients who did not achieve clinical complete remission 6-8 weeks after neoadjuvant radiochemotherapy and refused surgery, radiotherapy was given in the first stage at the doses of GTV 50Gy/25f and CTV 45Gy/25f for 5-6 weeks. In the second stage, MR linear accelerator was used for radiotherapy boosting, and the dose was GTV 30Gy/15f for 3 weeks.

Primary Outcome Measures

Name	Time	Method
3-year progression free survival rate	3-year after enrollment	Percentage of survive patients with no disease progression or death after 3 years from enrollment.

Secondary Outcome Measures

Name	Time	Method
3-year distant metastasis rate	3-year after enrollment	The percentage of patients with distant metastasis.
3-year overall survival rate	3-year after enrollment	The percentage of patients survive 3 years after enrollment
3-year stoma free survival rate	3-year after enrollment	Percentage of patients survive with no enterostomy after 3 years from enrollment.
3-year local regeneration rate	3-year after enrollment	Percentage of patients with no local tumor regeneration after 3 years from enrollment.
3-year disease-free survival rate	3-year after enrollment	The percentage of patients survive with no disease after 3 years from enrollment
Patients' quality of life scale	Before and during treatment. 3-month, 6-month, 1-year, 3-year after enrollment.	Patients' quality of life scale
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	During treatment. 3-month, 6-month, 1-year, 3-year after treatment.	Acute and chronic toxic and side effects

Trial Locations

Locations (1)

Sun Yat-sen University Cancer Center; 🇨🇳 Guangzhou, Guangdong, China