PD-1 Antibody Following Preoperative Chemoradiotherapy for Locally Advanced pMMR/MSS Rectal Cancer

PD-1 Antibody as a Sequential Therapy Following Preoperative Chemoradiotherapy for Locally Advanced pMMR/MSS Rectal Cancer: an Open, Multi-center, Phase II Clinical Trial

In this open-label phase II study, patients will be scheduled for neoadjuvant treatment with PD-1 antibody following preoperative Chemoradiotherapy with capecitabine for pMMR/MSS rectal cancer staged as locally advanced (cT3-T4N+/-M0 for rectal cancer). This treatment will be given during the window period until surgical resection of the tumor.

Study Overview

• Status: Active, not recruiting
• Conditions: Colorectal Carcinoma
• Intervention / Treatment: Drug: PD-1 antibody

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • 651 Dongfeng Road East

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients who personally provided written consent for participation in the study
• Treatment-naive patients with rectal cancer, in whom the inferior margin of the tumor was at a distance of 12 cm or less from the AV before CRT
• Primary rectal cancer histopathologically confirmed to be adenocarcinoma
• Clinical stage of T3,and T4 ,N any,M0,before CRT
• Macroscopic radical resection could be feasible, based on diagnostic imaging before CRT
• Patients with the ECOG performance status of 0 or 1 at the time of enrollment
• Patients without distant metastasis on the imaging test before CRT
• Preoperative biopsy of tumor immunohistochemistry TPS>1% or CPS>1
• Life expectancy of greater than 2 years
• No signs of intestinal obstruction; or the obstruction has been relieved after the proximal colostomy operation
• Hematology: WBC>4000/mm3; PLT>100000/mm3; Hb>10g/dL
• Liver function: SGOT and SGPT are less than 1.5 times the normal value; bilirubin is less than 1.5mg/dL
• Renal function: creatinine <1.8mg/dL Others: non-pregnant or breast-feeding women; no other malignant diseases (except for non-melanoma or cervical carcinoma in situ) within 5 years or during the same period; no mental illness that causes the inability to obtain informed consent; no other serious diseases that can shorten the survival time disease.
• Have not received rectal surgery in the past;
• Have not received chemotherapy or radiotherapy in the past;
• Have not received biological treatment in the past;
• Past endocrine therapy: unlimited.

Exclusion Criteria:

• Rectal cancer with unstable microsatellite (MSI or dMMR);
• Preoperative biopsy of tumor immunohistochemistry TPS≤1% or CPS≤1
• Known history of human immunodeficiency virus (HIV) or chronic hepatitis B or C (high copy viral DNA);
• Autoimmune diseases;
• Other active clinical serious infections (>NCI-CTC version 3.0);
• Patients in clinical phase I;
• There is evidence that there is distant metastasis before surgery;
• Cachexia, decompensation of organ function;
• Have a history of pelvic or abdominal radiotherapy;
• Multiple primary cancers;
• Patients who need treatment for seizures (such as steroids or anti-epileptic treatment);
• Have a known additional malignant tumors within 5 years. Exceptions include basal cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer;
• Chronic inflammatory bowel disease, intestinal obstruction;
• Drug abuse and medical, psychological or social conditions may interfere with patients' participation in research or have an impact on the evaluation of research results;
• Known or suspected to be allergic to the study drug or to any drug given in connection with this test;
• Any unstable conditions or situations that may endanger patient safety and compliance

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PD-1 antibody + capecitabine + radiation	Drug: PD-1 antibody; Capecitabine:Dose of 1650mg/m2,14days; Radiation:50Gy/25 fractions;IBI308: 200mg on day1 of each cycle, 3 cycles; Surgical therapy:The resection (LAR), intersphincteric resection (ISR), or abdominoperineal resection (APR)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological complete response	Pathological complete response will be evaluated with American Joint Committee on Cancer (AJCC) Cancer Staging	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival (OS)	3 years
Relapse-free survival (RFS)	3 years
Clinical complete response (CCR)	1 year

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: Fudan University; Liaoning Tumor Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Anticipated): December 31, 2024
• Study Completion (Anticipated): December 31, 2026

Study Registration Dates

• First Submitted: April 4, 2021
• First Submitted That Met QC Criteria: April 4, 2021
• First Posted (Actual): April 6, 2021

Study Record Updates

• Last Update Posted (Estimate): January 11, 2023
• Last Update Submitted That Met QC Criteria: January 9, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Antibodies
• Other Study ID Numbers: B2019-092

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No