Preoperative Short-course Radiation Followed by Envafolimab Plus CAPEOX for MSS Locally Advanced Rectal Adenocarcinoma (PRECAM)

NCT05216653 | Completed Phase 2

• 1 other identifier: 20220111-8
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

Short-course radiotherapy combined with immunotherapy may bring revolutionary changes to the preoperative neoadjuvant treatment mode for locally advanced rectal cancer. According to the existing theory, the use of PD-L1 monoclonal antibody after short-course radiotherapy may be the best solution. In this study, the investigators will perform single-cell sequencing of participants tissue samples, fully explore the multi-dimensional omics information of tumors and microenvironments, explore the characteristics of the treatment benefit population, and try to construct an efficacy prediction model to screen the treatment benefit population early and implement precise treatment.

Conditions

MSS Locally Advanced Rectal Adenocarcinoma

Keywords

Radiation; Envafolimab

Outcome Measures

Primary Outcomes (1)

• The primary objective of the study is to evaluate the pathologic complete response (pCR) rate following short-course radiation then Envafolimab Plus CAPEOX

  pCR was defined as the absence of viable tumour cells in the resected primary tumour specimen and all sampled regional lymph nodes (ypT0N0).

  Up to 10 weeks (once surgery is done)

Secondary Outcomes (6)

• Tumor regression grade following short-course radiation then Envafolimab Plus CAPEOX as assessed by AJCC/CAP TRG system

  Up to 10 weeks (once surgery is done)

• The proportion of participants who remain survival at 3 years

  Up to 3 years

• The proportion of participants who remain progression free at 3 years

  Up to 3 years

• Number of participants with treatment-related adverse events as assessed by NCI-CTCAE v5.0

  Up to 3 years

• Surgical Complications of total mesorectal resection procedure for patients after short-course radiation then Envafolimab Plus CAPEOX as assessed by Clavien-Dindo classification

  Up to 24 weeks

Study Arms (1)

Preoperative Short-course Radiation followed by Envafolimab plus CAPEOX

EXPERIMENTAL

The enrolled patients with MSS-type advanced middle-low rectal cancer will receive a combined regimen of neoadjuvant chemoradiotherapy combined with immunotherapy and total mesorectal excision (TME surgery). 1. Radiotherapy uses a short-range mode, irradiating the primary tumor and high-risk areas with dose of 25 Gy. 2. After radiotherapy, PD-L1 antibody (150mg/week, subcutaneous injection × 6 weeks) immunotherapy combined with two courses of CAPEOX chemotherapy was performed. 3. Two weeks after the end of the combined treatment plan in step 2), TME surgery is performed.

Drug: Envafolimab; Drug: Oxaliplatin; Drug: Capecitabine; Radiation: Short-course Radiation; Procedure: TME surgery, total mesorectal excision

Interventions

Envafolimab DRUG

This product is administered by subcutaneous injection. The recommended dose of subcutaneous injection is 150 mg, administered weekly (QW).

Also known as: KN053

Preoperative Short-course Radiation followed by Envafolimab plus CAPEOX

Oxaliplatin DRUG

130mg/m2，ivgtt，d1

Preoperative Short-course Radiation followed by Envafolimab plus CAPEOX

Capecitabine DRUG

1000mg/m2，po，bid，d1-14

Preoperative Short-course Radiation followed by Envafolimab plus CAPEOX

Short-course Radiation RADIATION

Short-course radiotherapy, using three-dimensional conformal or intensity-modulated radiotherapy, the dose is divided into 5Gy/f, the total dose is 25Gy/5f, 1f/d, and the irradiation is completed within 7 days.

Preoperative Short-course Radiation followed by Envafolimab plus CAPEOX

TME surgery, total mesorectal excision PROCEDURE

The surgical method can choose open, laparoscopic or robotic according to the specific condition of the patient.

Preoperative Short-course Radiation followed by Envafolimab plus CAPEOX

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who are willing to receive neoadjuvant therapy.
• ≧18 years old.
• Diagnosed by digital rectal examination, colonoscopy, and high-resolution MRI of the pelvis, the tumor is less than or equal to 12 cm from the anus.
• Histologically diagnosed as rectal adenocarcinoma.
• The clinical staging by pelvic contrast-enhanced CT and pelvic high-resolution MRI were cT2-4a N+, cT3/T4a N0.
• MMR protein detection or MSI gene detection of rectal cancer specimens confirmed pMMR or MSS before treatment .
• The patient has good compliance and can come to the hospital for re-examination as required.
• ECOG Scale of Performance Status score 0-1 point.
• Have not received anti-tumor and immunotherapy before enrollment.
• Laboratory inspections must meet the following standards:
• White blood cell count\>3.5×109/L, absolute value of neutrophils\>1.8×109/L, platelet count ≥75×109/L, hemoglobin ≥100g/L;
• INR≤1.5, and APTT≤1.5 times the upper limit of normal or partial prothrombin time (PT) ≤1.5 times the upper limit of normal;
• Total bilirubin ≤ 1.25 times the upper limit of normal; ALT and AST \< 5 times the upper limit of normal;
• h creatinine clearance \>50mL/min or serum creatinine \<1.5 times the upper limit of normal.
• Voluntarily participate in this study and sign the informed consent.

You may not qualify if:

• History of other malignant diseases in the past 5 years.
• Patients with metastases from other sites (stage IV patients).
• Patients with clinical staging of T1-2N0 or T4b, or positive lateral lymph nodes by pelvic contrast-enhanced CT and pelvic high-resolution MRI.
• Patients with intestinal obstruction, intestinal perforation, intestinal bleeding, etc. requiring emergency surgery.
• Known allergic to oxaliplatin, capecitabine, PD-L1 monoclonal antibody and other drugs.
• Pathologically suggested signet ring cell carcinoma and mucinous adenocarcinoma.
• dMMR or MSI-H patients.
• The patient is accompanied by any unstable systemic disease, including but not limited to: severe infection, uncontrolled diabetes, hypertension uncontrolled by medication, unstable angina, cerebrovascular accident or transient cerebral ischemia, myocardial Infarction, congestive heart failure, severe cardiac arrhythmia requiring medication, hepatic, renal or metabolic disease; disease affecting the patient's life.
• The disease (such as mental illness, etc.) or condition (such as alcoholism or drug abuse, etc.) associated with the patient will increase the risk of the patient receiving the trial drug treatment or affect the patient's compliance with the trial requirements, or may confuse the research results.
• Active autoimmune disease that may worsen while receiving immunostimulants.
• Known history of positive HIV test or known acquired immunodeficiency syndrome.
• Patients who are using immunosuppressive agents, except for the following conditions:
• Intranasal, inhaled, topical steroids, or topical steroid injections (eg, intra-articular injections);
• Physiological doses of systemic corticosteroids ≤10 mg/day prednisone or equivalent;
• Steroids used to prevent allergic reactions (eg, before CT scan).

Sponsors & Collaborators

• Sir Run Run Shaw Hospital: lead

Study Sites (1)

Sir Run Run Shaw Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310016, China

Location

MeSH Terms

Interventions

envafolimab; Oxaliplatin; Capecitabine

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Sheng Dai, MD&PhD

  Sir Run Run Shaw Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice director, Colorectal Surgery

Study Record Dates

• First Submitted: January 14, 2022
• First Posted: January 31, 2022
• Study Start: April 7, 2022
• Primary Completion: March 31, 2023
• Study Completion: March 5, 2025
• Last Updated: March 13, 2025

Record last verified: 2025-03

Locations

CN (1)