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

Overview

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.

Interventions

• Radiation Magnetic resonance guided radiotherapy
  Radical radiotherapy boosting for low rectal cancer through magnetic resonance guided radiotherapy linear accelerator.
• Drug Chemotherapy
  For patients with AJCC stage II and III and age \< 72 years old, Capox ×6→capecitabine×2. Detailed usage: Oxaliplatin 130mg/m2 (reduced to 100mg/m2 during concurrent chemoradiotherapy), intravenous administration, d1. Capecitabine 1000mg / m2, twice a day, d1-14. Repeated every 3 weeks. For patients aged ≥ 72 years, or the competent physician judges that the patients cannot tolerate dual drug combined chemotherapy, capecitabine ×8 courses. For patients with AJCC stage I, capecitabine ×4 cours

Primary outcome measures

• 3-year progression free survival rate [Time frame: 3-year after enrollment]

Secondary outcome measures (7)

• 3-year stoma free survival rate [Time frame: 3-year after enrollment]
• 3-year local regeneration rate [Time frame: 3-year after enrollment]
• 3-year disease-free survival rate [Time frame: 3-year after enrollment]
• 3-year distant metastasis rate [Time frame: 3-year after enrollment]
• 3-year overall survival rate [Time frame: 3-year after enrollment]
• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [Time frame: During treatment. 3-month, 6-month, 1-year, 3-year after treatment.]
• Patients' quality of life scale [Time frame: Before and during treatment. 3-month, 6-month, 1-year, 3-year after enrollment.]

Eligibility criteria

Inclusion criteria

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

Exclusion criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

China · 1 center

• Sun Yat-sen University Cancer Center — Guangzhou

Publications

• Wang Q, Zhang S, Zhou C, et al. Efficacy and safety of high dose radiotherapy for the treatment of locally advanced rectal cancer. International Journal of Radiation Oncology Biology Physics. 2020. 108(3): e644-e645
• Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015 Mar;65(2):87-108. doi: 10.3322/caac.21262. Epub 2015 Feb 4. PMID 25651787
• Glimelius B, Tiret E, Cervantes A, Arnold D; ESMO Guidelines Working Group. Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013 Oct;24 Suppl 6:vi81-8. doi: 10.1093/annonc/mdt240. No abstract available. PMID 24078665
• Galandiuk S, Wieand HS, Moertel CG, Cha SS, Fitzgibbons RJ Jr, Pemberton JH, Wolff BG. Patterns of recurrence after curative resection of carcinoma of the colon and rectum. Surg Gynecol Obstet. 1992 Jan;174(1):27-32. PMID 1729745
• Sebag-Montefiore D, Stephens RJ, Steele R, Monson J, Grieve R, Khanna S, Quirke P, Couture J, de Metz C, Myint AS, Bessell E, Griffiths G, Thompson LC, Parmar M. Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet. 2009 Mar 7;373(9666):811-20. doi: 10.1016/S0140-6736(09)60484 PMID 19269519
• Heald RJ, Ryall R. Recurrent cancer after restorative resection of the rectum. Br Med J (Clin Res Ed). 1982 Mar 13;284(6318):826-7. doi: 10.1136/bmj.284.6318.826-e. No abstract available. PMID 6802248
• Sauer R, Becker H, Hohenberger W, Rodel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R; German Rectal Cancer Study Group. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004 Oct 21;351(17):1731-40. doi: 10.1056/NEJMoa040694. PMID 15496622
• Sauer R, Liersch T, Merkel S, Fietkau R, Hohenberger W, Hess C, Becker H, Raab HR, Villanueva MT, Witzigmann H, Wittekind C, Beissbarth T, Rodel C. Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol. 2012 Jun 1;30(16):1926-33. doi: 10.1200/JCO.2011 PMID 22529255

Identifiers

NCT: NCT05338866 · 2021-FXY-489

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗