Clinical trial NCT05338866: Chemotherapy Combined With High-dose Radiotherapy for Low Rectal Cancer Using MR Guided Linear Accelerator
Official title: Chemotherapy Combined With High-dose Radiotherapy for Low Rectal Cancer Using Magnetic Resonance Guided Radiotherapy Linear Accelerator：A Prospective Phase 2 Trial
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Rectal Cancer
Keywords: Lower rectal cancer
Magnetic resonance imaging guided radiation therapy
High-dose radiotherapy
Toxic and side effects
Quality of life score
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2022-04-21
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with lower rectal cancer who refuse surgery for various reasons or are not suitable for surgery due to systemic diseases.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 3-year progression free survival rate
timeFrame: 3-year after enrollment
Secondary outcomes:
measure: 3-year stoma free survival rate
timeFrame: 3-year after enrollment
measure: 3-year local regeneration rate
timeFrame: 3-year after enrollment
measure: 3-year disease-free survival rate
timeFrame: 3-year after enrollment
measure: 3-year distant metastasis rate
timeFrame: 3-year after enrollment
measure: 3-year overall survival rate
timeFrame: 3-year after enrollment
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
timeFrame: During treatment. 3-month, 6-month, 1-year, 3-year after treatment.
measure: Patients' quality of life scale
timeFrame: Before and during treatment. 3-month, 6-month, 1-year, 3-year after enrollment.
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Yuanhong Gao, PhD
role: PRINCIPAL_INVESTIGATOR
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