NCT04405206

Total Neoadjuvant Therapy Followed by 'Watch and Wait' Approach or Organ Preservation for Low-risk Rectal Cancer

Total Neoadjuvant Therapy Followed by 'Watch and Wait' Approach or Organ Preservation for MRI Stratified Low-risk Rectal Cancer: a Multi-center, Prospective, Single-arm Phase II Trial.

• Status: Unknown
• Phase: —
• Study type: Observational
• Enrollment: 54 (estimated)
• Sponsor: Peking University Cancer Hospital & Institute · Academic / Other
• Sex: All
• Age: 18 Years – 85 Years
• Healthy volunteers: Not accepted

Summary

Aim: To investigate the safety and efficacy of organ preservation (OP) with watch-and-wait strategy (W\&W) or local excision (LE) in MRI stratified low-risk rectal cancer treated by total neoadjuvant treatment. Meanwhile we will look into the role of ctDNA in the prediction of regrowth and metastasis in the wait and wait process. Methods: Low-risk rectal cancer with following MRI features are recruited: mid-low tumor, mrT2-3b, MRF(-), EMVI(-), differentiation grade 1-3. Patients will receive IMRT 50.6Gy/22f with concurrent capecitabine and 4 cycles of consolidation CAPEOX. Patients with cCR/near-cCR were recommended for 'watch \& wait' approach or local excision (LE). The OPR and sphincter preservation rate (SPR) at 2 years will be analyzed. As the extension of PKUCH-R01, BJCC-R01 trial will upgrade to a multi-center research enrolled 3 other colorectal center in Beijing.

Detailed description

Neoadjuvant chemoradiotherapy (nCRT), total mesorectal excision and adjuvant chemotherapy comprise the standard treatment for locally advanced rectal cancer, following which 15-30% patients achieved pathological complete response need to receive the removal of rectum without residual tumor and suffer significant functional impairment even after sphincter preservation. Adjuvant chemotherapy is also questioned for its benefit for prolonged survival through the data from various studies. More evidence demonstrated that organ-preservation (e.g. non-operative management or local excision) for patients with clinical complete response (cCR) or near-cCR following nCRT had similar survival when compared with those received standard care. This study is designed to investigate the efficacy of neoadjuvant intensity modulated nCRT with concurrent capecitabine plus consolidation CapeOX for T2/DWI/Enhanced MRI defined cT2-T3b mid-low rectal cancer without threatening mesorectal fascia or extramural vascular invasion (EMVI) or mrN2 disease. According to the response to treatment evaluated by multi-modal assessment including digital exam, T2/DWI/Enhanced MRI, endoscopy and serum CEA test, patients will receive tailored operative management like local excision or total mesorectal excision, or non-operative management. Intention to treatment was also allowed in this study. Firstly, the investigators will observe the organ preservation rate at 2 years. Endpoints for organ-preservation like non-regrowth DFS, stoma-free survival and other conventional survival outcomes (DFS, OS) would be further collected. The short-term and long-term QoL will be measured in all patients. . Our baseline data showed the 48% of locally advanced rectal cancers could be downstaged to stage ypT0-2N0 following IMRT with concurrent capecitabine. We hypothesize that at least 24% of rectal cancers could be candidates for LE or NOM after IMRT and the rectum preservation rate will increase to 40% in low-risk rectal cancers by LE or NOM following IMRT plus consolidation CapeOX at 2 years. As a superiority design, this study need to recruit 64 patients to test this hypothesis, with 85% power (exact binomial test for proportions, alpha = 5 %, one-sided), If the number of responses is 22 or more, the hypothesis that P \<= 0.240 is rejected. We anticipate about 10 % loss to follow-up, so we will recruit an additional 8 patients and the study will recruit 72 patients in all.

Conditions

• Rectum Cancer

Interventions

Type	Name	Description
DRUG	Oxaliplatin	OXA 130mg/m2
DRUG	Capecitabine	Cape 1000mg/m2
RADIATION	intensity modulated radiotherapy	IMRT 50.4Gy/22f
PROCEDURE	DRE-Endoscopy-MRI-CEA	examination process in follow up
PROCEDURE	Nonoperative Management	Watch and Wait
PROCEDURE	Local excision	For ymriT1N0 and near-cCR patients，LE is optional.
PROCEDURE	Total Mesorectal Excision	Standard TME surgery openly or laporoscopically
BEHAVIORAL	Quality of Life Questionnaires	QLQ C30 and QLQ CR29

Timeline

• Start date: 2020-05-25
• Primary completion: 2023-12-30
• Completion: 2023-12-30
• First posted: 2020-05-28
• Last updated: 2020-10-14

Locations

1 site across 1 country: China