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

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

NCT ID: NCT05969847

Condition: Rectal Cancer

Conditions: Official terms:
Rectal Neoplasms
Capecitabine
Oxaliplatin

Conditions: Keywords:
Locally advanced very low rectal cancer
Total neoadjuvant therapy
Hypofraction radiotherapy
CAPOX
Envafolimab
Local excision

Study type: Interventional

Study phase: Phase 2

Overall status: Not yet recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Radiation
Intervention name: split-course hypofraction radiotherapy
Description: After reaching a cumulative radiotherapy dose of 25Gy in the entire pelvic cavity (PTV1), the treatment field was subsequently narrowed to solely focus on the primary tumor (PTV2), with a total dose of 35Gy administered. All patients will undergo fractionated radiotherapy, following a regimen of 7Gy per fraction, delivered every 3 weeks for five cycles.
Arm group label: split-course hypofraction radiotherapy plus CAPOX and Envafolimab followed by local excision

Other name: hypofraction radiotherapy

Intervention type: Drug
Intervention name: CAPOX
Description: Drug: Oxaliplatin,130mg/m2，ivgtt，d1,for 6 cycles. Drug: Capecitabine,1000mg/m2，po，bid，d1-14, for 6 cycles.
Arm group label: split-course hypofraction radiotherapy plus CAPOX and Envafolimab followed by local excision

Other name: Capecitabine+Oxaliplatin

Intervention type: Drug
Intervention name: Envafolimab
Description: Envafolimab is administered by subcutaneous injection. The recommended dose is 300 mg per 3 weeks (Q3W) for 6 cycles.
Arm group label: split-course hypofraction radiotherapy plus CAPOX and Envafolimab followed by local excision

Other name: KN035

Intervention type: Procedure
Intervention name: Local excision
Description: Local full-thickness resection is employed for patients with clinical complete response (cCR) or near-clinical complete response (ncCR) following TNT.
Arm group label: split-course hypofraction radiotherapy plus CAPOX and Envafolimab followed by local excision

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-clinical complete response (ncCR) after undergoing TNT, an organ-preserving strategy involving local full-thickness resection was implemented.

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 advanced very low rectal cancer. However, the long-term presence of a colostomy following an abdominoperineal resection (APR) significantly impacts the quality of life for patients. Additionally, studies have revealed that 11.8-22% of rectal cancer patients who underwent APR after neoadjuvant chemoradiotherapy (nCRT) achieved a pathological complete response (pCR). Conversely, 11-52% of patients with pCR after nCRT for rectal cancer ultimately underwent APR surgery. Intersphincter resection (ISR) offers a highly beneficial surgical approach that preserves the anal sphincter, particularly for individuals with locally advanced very low rectal cancer. The patient's postoperative quality of life was significantly affected by severe low anterior resection syndrome (LARS), sexual dysfunction, and voiding dysfunction. This study represents an exploratory phase II clinical trial in which 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 undergoing 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. This study aims to investigate the effectiveness and safety of organ preservation using the local resection approach in patients with locally advanced very low rectal cancer. By implementing this approach, the study aims to improve the quality of life for patients who achieve pathological complete response (pCR), thereby avoiding the need for conventional abdominoperineal resection (APR) and intersphincteric resection (ISR) procedures. Additionally, this study aims to address the issue of local regrowth associated with the "watch & wait" strategy and propose a novel treatment strategy for rectal-sparing surgery in patients with locally advanced very low rectal cancer.

Criteria for eligibility:
Criteria:
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 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

Gender: All

Minimum age: 18 Years

Maximum age: 75 Years

Healthy volunteers: No

Locations:

Facility:
Name: Pan Chi

Address:
City: Fuzhou
Zip: 350001
Country: China

Contact:
Last name: Pan Chi, MD

Phone: +8613675089677
Email: cp3169@163.com

Contact backup:
Last name: Jiabin Zheng

Phone: +8613365910080
Email: xhyykjk@163.com

Start date: August 15, 2023

Completion date: December 31, 2027

Lead sponsor:
Agency: 池畔
Agency class: Other

Source: Fujian Medical University Union Hospital

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05969847