Organ Preservation Following Enverolimab-based Total Neoadjuvant Therapy for Locally Advanced Very Low Rectal Cancer

Phase 2

Not yet recruiting

• Conditions: Rectal Cancer
• Interventions: Radiation: split-course hypofraction radiotherapy; Drug: CAPOX; Drug: Envafolimab; Procedure: Local excision

• Registration Number: NCT05969847
• Lead Sponsor: 池畔

Brief Summary

Patients diagnosed with locally advanced very low rectal cancer were chosen to participate in a comprehensive neoadjuvant therapy (TNT) protocol. This treatment regimen consisted of preoperative fractionated radiotherapy (5×7Gy) combined with 6 cycles of CAPOX chemotherapy and enverolimab. For patients who achieved clinical complete response (cCR) or near-cl...

Detailed Description

Locally advanced very low rectal cancer poses significant challenges in rectal cancer treatment. Presently, the prevailing approach in clinical practice involves neoadjuvant chemoradiotherapy in conjunction with total mesorectal excision (TME). Historically, abdominoperineal resection (APR) has been the conventional surgical procedure for managing locally ad...

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Status Verified: 2023-07
• Study First Submitted: 2023-07-23
• Study First Submitted QC: 2023-07-23
• Last Update Submitted: 2023-07-23
• Study First Posted: 2023-08-01
• Last Update Posted: 2023-08-01
• Study Start: 2023-08-15
• Primary Completion: 2027-12-31
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 72

Inclusion Criteria

1. Aged 18-75.

2. Histopathology confirmed the rectal adenocarcinoma,cT3-4N0 or cT1-4N1-2. The tumor's lower margin ≤ 2cm from the anorectal ring's upper edge (based on MRI measurement).

3. Eastern tumor cooperation group (ECOG) status:0-2.

4. American Association of Anesthesiologists (ASA) status: I-III.

5. No previous systemic therapy, including chemotherapy, immunotherapy, or radiotherapy for rectal cancer.

6. No previous history of pelvic radiotherapy.

7. Sufficient organ function based on the following parameters:

   An absolute neutrophil count≥ 1.5 × 109 / L, a thrombocyte count ≥ 100 × 109/ L, a glomerular filtration rate (calculated using the Cockcroft-Gault formula) with a creatinine level ≤ 1.5 × ULN or a creatinine clearance > 50ml/min, and AST and ALT levels ≤ 2.5 × ULN or a total bilirubin level ≤ 1.5 × ULN.

8. Effective contraception during the study.

9. Patients are willing and able to comply with the protocol during the study period.

10. Patients with written informed consent

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Exclusion Criteria

1. Poorly differentiated adenocarcinoma, mucinous adenocarcinoma, signet ring cell carcinoma, and adenocarcinoma developed from inflammatory bowel disease.
2. Metastasis to para-aortic, lateral, or inguinal lymph nodes has been identified.
3. Suspected distant metastasis in organs other than para-aortic, lateral, or inguinal lymph nodes is being considered.
4. Known hypersensitivity to platinum drugs or capecitabine.
5. Patients receiving concomitant treatment with drugs that interact with capecitabine or oxaliplatin (such as flucytosine, phenytoin, and warfarin).
6. According to the New York Heart Association (NYHA) classification, III or IV heart failure, and angina pectoris have occurred in the past six months.
7. Uncontrolled active infection or severe concomitant systemic disease.
8. Patients who need immunosuppressive therapy for organ transplantation.
9. Uncontrolled epilepsy or mental illness.
10. Pregnant or lactating female patients.
11. Non-compliance or researchers believe that the patient will not be able to complete the entire trial

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
split-course hypofraction radiotherapy plus CAPOX and Envafolimab followed by local excision	CAPOX	Patients diagnosed with locally advanced very low rectal cancer were chosen to undergo a total neoadjuvant therapy (TNT) regimen. This regimen consisted of preoperative fractionated radiotherapy (5×7Gy) combined with 6 cycles of CAPOX chemotherapy and enverolimab. For patients who achieved clinical complete response (cCR) or near-clinical complete response (ncCR) after TNT, an organ-preserving strategy involving local full-thickness resection was implemented. Patients who achieve non-clinical complete response are subjected to traditional TME surgery.
split-course hypofraction radiotherapy plus CAPOX and Envafolimab followed by local excision	Local excision	Patients diagnosed with locally advanced very low rectal cancer were chosen to undergo a total neoadjuvant therapy (TNT) regimen. This regimen consisted of preoperative fractionated radiotherapy (5×7Gy) combined with 6 cycles of CAPOX chemotherapy and enverolimab. For patients who achieved clinical complete response (cCR) or near-clinical complete response (ncCR) after TNT, an organ-preserving strategy involving local full-thickness resection was implemented. Patients who achieve non-clinical complete response are subjected to traditional TME surgery.
split-course hypofraction radiotherapy plus CAPOX and Envafolimab followed by local excision	split-course hypofraction radiotherapy	Patients diagnosed with locally advanced very low rectal cancer were chosen to undergo a total neoadjuvant therapy (TNT) regimen. This regimen consisted of preoperative fractionated radiotherapy (5×7Gy) combined with 6 cycles of CAPOX chemotherapy and enverolimab. For patients who achieved clinical complete response (cCR) or near-clinical complete response (ncCR) after TNT, an organ-preserving strategy involving local full-thickness resection was implemented. Patients who achieve non-clinical complete response are subjected to traditional TME surgery.
split-course hypofraction radiotherapy plus CAPOX and Envafolimab followed by local excision	Envafolimab	Patients diagnosed with locally advanced very low rectal cancer were chosen to undergo a total neoadjuvant therapy (TNT) regimen. This regimen consisted of preoperative fractionated radiotherapy (5×7Gy) combined with 6 cycles of CAPOX chemotherapy and enverolimab. For patients who achieved clinical complete response (cCR) or near-clinical complete response (ncCR) after TNT, an organ-preserving strategy involving local full-thickness resection was implemented. Patients who achieve non-clinical complete response are subjected to traditional TME surgery.

Primary Outcome Measures

Name	Time	Method
Organ preservation	36 months	The rectum is intact, owing to no radical total mesorectal excision (TME), curative (R0) salvage surgery by local excision (LE), and no permanent stoma (including a never reversed protective stoma or a stoma owing to toxicities and/or poor functional outcomes).

Secondary Outcome Measures

Name	Time	Method
Local recurrence rate	36months	The proportion of patients in all subjects within 3 years from the start of the surgery to detection of a tumor involving the bowel wall only that occurs after LE or TME
Local regional recurrence rate	36 months	The proportion of patients in all subjects within 3 years from the start of the surgery to detection of a tumor involving either the bowel wall, mesorectum, and/or pelvic organs that occurs after LE or TME
Disease-free survival	36 months	The proportion of patients in all subjects within 3 years from the start of the surgery to recurrence, distant metastsis, or death from any cause (whichever occurs first)
ypT0-1 rate	36 months	The proportion of subjects with primary rectal cancer assessed by hematoxylin and eosin staining including no evidence of primary tumor (T0) or carcinoma in situ: intramucosal carcinoma (invading lamina propria, not infiltrating muscularis mucosa) (Tis) or tumor invading submucosa (T1) (ypT0-1 based on the latest UICC/AJCC staging system)
Acute and late toxicity	36 months	Acute and late toxicity, Incidence of Treatment-Emergent Adverse Events assessment according to NCICTCAE V.5.0
Pathological complete response (pCR) rate	36 months	Proportion of subjects with primary rectal cancer and all sampled lymph nodes who did not find any invasive carcinoma and high-grade intraepithelial neoplasia/severe dysplasia after assessment by hematoxylin and eosin staining (Judged as ypT0N0 stage according to the latest UICC/AJCC staging system)
Quality of life-based on EORTC QLQ-C30 and EORTC QLQ-CR29	baseline, 3 months, 12 months, 24 months, and 36 months after LE or TME	Quality of life measured using EORTC QLQ-C30 and EORTC QLQ-CR29
Anorectal function	baseline, 3 months, 12 months, 24 months, and 36 months after LE or TME	Anorectal function based on LARS score

Trial Locations

Locations (1)

Pan Chi; 🇨🇳 Fuzhou, Fujian, China