Single-arm, Single-center, Exploratory Phase II Clinical Study of Envafolimab Combined With Chemoradiotherapy in the Treatment of Locally Advanced pMMR/MSS Rectal Cancer

NCT06239870 | Unknown Phase 2 DMC

• 2 other identifiers: SLKYLX2023-006STLKY0036
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

Preoperative radiotherapy combined with 5-fluorouracil/capecitabine is currently the standard treatment for locally advanced rectal cancer. Although this strategy effectively reduces the risk of local recurrence, it fails to effectively improve the overall survival rate of patients . The root cause is that 5-fluorouracil/capecitabine based local radiotherapy is not effective in controlling potential micrometastases. Therefore, many studies try to combine preoperative radiotherapy with more intense chemotherapy and targeted drugs at the same time, as well as induction chemotherapy before preoperative radiotherapy and consolidation chemotherapy after, in order to obtain better efficacy. However, a number of studies have shown that increasing cytotoxic drugs fail to effectively improve pathologic complete response rate (pCR) and long-term survival rate, and significantly increase therapeutic toxicity . Therefore, the idea of trying to increase the efficacy of cytotoxic drugs by accumulating them does not work.Based on the use of PD-1/PD-L1 antibody in colorectal cancer and other solid tumors, and referring to the scheme of PD-1/PD-L1 antibody combined with radiotherapy in other solid tumors, we added envafolimab to local radiotherapy for advanced rectal cancer for exploration, with a view to further improving the pCR rate and long-term survival of patients.

Conditions

Envafolimab Combined With Chemoradiotherapy in the Treatment of Locally Advanced pMMR/MSS Rectal Cancer

Keywords

Local progressive stage; Rectal cancer; Full neoadjuvant therapy; pMMR/MSS; Envafolimab

Outcome Measures

Primary Outcomes (1)

• pCR

  Pathological complete response

  3 months

Secondary Outcomes (1)

• TRG

  3 months

Study Arms (1)

neoadjuvant therapy

EXPERIMENTAL

1. Induction therapy stage: chemotherapy combined with immunotherapy for 2 cycles: Envafolimab: 200mg, subcutaneous injection, Q2W, 2 cycles; mFOLFOX6: Q2W, 2 cycles (concurrent administration of envollizumab on the first day of chemotherapy). 2. Concurrent chemoradiotherapy: long-term chemoradiotherapy combined with immunotherapy for 3 cycles: radiation therapy: 50Gy/25f, 2Gy every day, 5 days a week for 5 weeks; Capecitabine: 825mg/m2 orally (1650mg/m2/d) twice a day in the morning and evening, 5 days a week, simultaneous with radiation therapy, for a total of 25 days; Envafolimab: 200mg, subcutaneous injection, Q2W, 3 cycles (Envafolimab was administered on day 1, day 15, and day 29 of radiotherapy). Iii. Consolidation treatment stage: chemotherapy combined with immunotherapy for 2 cycles: Envafolimab: 200mg, subcutaneous injection, Q2W, 2 cycles; mFOLFOX6: Q2W, 2 cycles. (Concurrent administration of envafolimab on the first day of chemotherapy).

Drug: Envafolimab combined with chemoradiotherapy in the whole course of neoadjuvant therapy

Interventions

Envafolimab combined with chemoradiotherapy in the whole course of neoadjuvant therapy DRUG

Each enrolled patient was given 2 cycles of induction chemotherapy combined with immunization, followed by immunization combined with chemoradiotherapy, and finally 2 cycles of consolidation chemotherapy combined immunization

neoadjuvant therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \) Disease characteristics
• Histologically confirmed rectal adenocarcinoma; Immunohistochemical confirmation as pMMR or/and pCR or/and NGS test as MSS;
• Tumor location within 12cm from anal margin;
• Locally advanced rectal cancer (stage II-III, i.e. cT3-4 and/or N+) as assessed by the UICC/AJCC TNM staging system (8th edition, 2017);
• \* Preoperative staging method: pelvic MRI/ transrectal ultrasound combined with preoperative staging.
• No signs of intestinal obstruction; Or intestinal obstruction has been relieved after proximal colostomy surgery;
• Preoperative chest, abdominal and pelvic CT to exclude distant metastasis. 2) Patient characteristics
• Age: 18 \~75 years old;
• Activity status score: ECOG 0-1;
• Life expectancy: more than 2 years;
• Hematology: WBC\>3500×106/L; PLT\>100000×106/L; Hb\>10g/dL;
• Liver function: SGOT and SGPT are less than 1.5 times of normal value; Bilirubin less than 1.5mg/dL;
• Kidney function: creatinine \<1.8mg/dL;
• Other: non-pregnant or breastfeeding women; No other malignant disease (other than non-melanoma or carcinoma in situ of the cervix) within 5 years or during the same period; Does not have a mental illness that prevents informed consent; There were no other serious diseases associated with shorter survival.
• Patients or family members can understand the study protocol and are willing to participate in the study, and sign a written informed consent;

You may not qualify if:

• CRC for microsatellite highly unstable (MSI-H) or mismatch repair protein expression deficiency (dMMR); Chronic hepatitis B or C with a history or active HIV infection (high copy of viral DNA);
• Autoimmune diseases;
• Other active clinical serious infections (\>NCI-CTC version 3.0);
• Stage I patients;
• Preoperative evidence of distant metastasis;
• Dysfluid, organ function decompensation;
• A history of pelvic or abdominal radiotherapy;
• Multiple primary cancers;
• Patients whose seizures require management (such as steroid or antiepileptic therapy);
• A history of other malignancies within 5 years, except for cured cervical carcinoma in situ or skin basal cell carcinoma;
• Chronic inflammatory bowel disease, intestinal obstruction; Substance abuse and medical, psychological or social conditions that may interfere with the patient's participation in the study or the evaluation of the findings;
• A known or suspected allergy to the study drug or to any drug administered in connection with this trial;
• Any unstable conditions or conditions that may compromise patient safety and compliance

Sponsors & Collaborators

• Yunnan Cancer Hospital: lead
• Beijing Bethune Charitable Foundation: collaborator

Study Sites (1)

Envafolimab

Kunming, Yunnan, 650000, China

RECRUITING

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Chemoradiotherapy

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Drug Therapy; Radiotherapy

Central Study Contacts

Yunfeng Li, master

CONTACT

13330445776; 13330445776@qq.com

Xuan Zhang, doctoral candidate

CONTACT

17387911546; 1025415085@qq.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2024
• First Posted: February 2, 2024
• Study Start: April 1, 2023
• Primary Completion: September 30, 2025
• Study Completion: September 30, 2025
• Last Updated: February 2, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)