PACE: PD-1 Antibody For dMMR/MSI-H Stage III Colorectal Cancer

NCT05236972 | Recruiting Phase 3

• 1 other identifier: B2021-361-01
• Study Type: interventional
• Target: 323
• Locations: 1 country
• Sites: 1

Brief Summary

In this open-label phase III study, patients with local advanced colon cancer (TanyN+ ,M0, dMMR/MSI-H, at least 10cm from the anus verge)will be scheduled to Group A: receive anti-PD-1 antibody alone (8 cycles, 200mg iv drip Q3W) and Group B (4 or 8 cycles of XELOX: oxaliplatin 130mg/m2 day 1, capecitabine 2000mg/m2 days 1-14, repeated every 21 days). The primary endpoint was 3 Disease-free survival; analyses were done based on all patients with post-randomization data.

Conditions

Colorectal Carcinoma

Keywords

dMMR/MSI-H

Outcome Measures

Primary Outcomes (1)

• Disease Free survival [ Time Frame: 3 years ]

  Disease-free survival (DFS) at 3 years. DFS is measured from the date of randomisation to the date of first relapse (radiological or clinical) or death from any cause.

  Up to 5 years

Secondary Outcomes (1)

• Overall Survival [ Time Frame: 5 years ]

  Up to 5 years

Study Arms (2)

Sintilimab

EXPERIMENTAL

Sintilimab 200mg iv drip Q3W for 8 courses

Drug: Sintilimab

XELOX

EXPERIMENTAL

Patients receive chemotherapy comprising oxaliplatin 130mg/m² ivdrip over 2 hours on day 1,capecitabine 2000 mg/m² on days 1-14, treatment repeats every 21 days for 4 or 8 courses

Drug: Oxaliplatin; Drug: capecitabine

Interventions

Sintilimab DRUG

Sintilimab 200mg iv drip Q3W

Sintilimab

Oxaliplatin DRUG

130 mg/m² iv drip over 2 hours on day 1, repeated every 21 days.

XELOX

capecitabine DRUG

1000 mg/m² po twice daily on days 1- 14 repeated every 21 days

XELOX

Eligibility Criteria

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

You may qualify if:

• Male or female subjects aged ≥18 years
• ECOG PS 0/1
• Histologically proven, stage III (i.e., any T, N1 or N2, M0) adenocarcinoma of the colon (as defined by the presence of the inferior pole of the tumour above the peritoneal reflection - that is, at least 10 cm from the anal margin).
• Fully surgically resected tumour with clear resection margins (i.e., \>1 mm)
• Locally confirmed defective mismatch repair (dMMR) tumour (as defined by the lack of staining on either the pre-operative biopsy samples or resection specimens of at least one of the following proteins: MLH1 (mutL homolog 1), MSH2 (mutS homologue 2), MSH6 (mutS homolog 6), PMS2
• Absence of metastases as shown by post-operative CT scan
• Absence of major post-operative complications or other clinical conditions that, in the opinion of the investigator, would contraindicate adjuvant chemotherapy

You may not qualify if:

• Rectal tumours (as defined by the presence of the inferior pole of the tumour below the peritoneal reflection - that is, \<15 cm from the anal margin).
• Inability to start adjuvant chemotherapy within 12 weeks after surgery
• Administration of neoadjuvant systemic chemotherapy or radiotherapy before surgical resection of colon cancer
• Prior organ transplantation, including allogeneic stem-cell transplantation
• Significant acute or chronic infections including, among others:
• known history of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) positive test for HBV (Hepatitis B) surface antigen or anti-HCV (Hepatitis C) antibody and confirmatory HCV RNA test
• Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent:
• Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible
• Subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses ≤10 mg/day of prednisone or equivalent
• Administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) are acceptable
• Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥3 NCI-CTCAE v4.0), any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma)
• Persisting toxicity related to prior therapy of Grade \>1 NCI-CTCAE v4.0; however, alopecia and sensory neuropathy Grade ≤2 is acceptable unless oxaliplatin administration is planned as part of the adjuvant treatment
• Pregnancy or lactation
• Known alcohol or drug abuse
• Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (\<6 months prior to enrollment), myocardial infarction (\<6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Second Affiliated Hospital, School of Medicine, Zhejiang University: collaborator
• West China Hospital: collaborator

Study Sites (1)

Sun Yat-sen University

Guangzhou, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

sintilimab; Oxaliplatin; Capecitabine

Condition Hierarchy (Ancestors)

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

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

Central Study Contacts

Peirong Ding, professor

CONTACT

+86-13543478645; dingpr@sysucc.org.cn

Zhenlin Hou

CONTACT

+86-17612057762; houzl@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 19, 2022
• First Posted: February 11, 2022
• Study Start: January 1, 2022
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 31, 2028
• Last Updated: December 30, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)