Clinical trial NCT05236972: PACE: PD-1 Antibody For dMMR/MSI-H Stage III Colorectal Cancer
Official title: Study of Sintilimab vs Standard Therapy in Participants With Mismatch Repair Deficient (dMMR) or Microsatellite Instability-High (MSI-H) Stage III Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Colorectal Carcinoma
Keywords: dMMR/MSI-H
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: Second Affiliated Hospital, School of Medicine, Zhejiang University
name: West China Hospital
First posted: 2022-02-11
Enrollment: 323
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Male or female subjects aged ≥18 years
2. ECOG PS 0/1
3. 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).
4. Fully surgically resected tumour with clear resection margins (i.e., \>1 mm)
5. 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
6. Absence of metastases as shown by post-operative CT scan
7. Absence of major post-operative complications or other clinical conditions that, in the opinion of the investigator, would contraindicate adjuvant chemotherapy

Exclusion Criteria:

1. 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).
2. Inability to start adjuvant chemotherapy within 12 weeks after surgery
3. Administration of neoadjuvant systemic chemotherapy or radiotherapy before surgical resection of colon cancer
4. Prior organ transplantation, including allogeneic stem-cell transplantation
5. 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
6. Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent:
7. Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible
8. 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
9. Administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) are acceptable
10. 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)
11. 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
12. Pregnancy or lactation
13. Known alcohol or drug abuse
14. 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
15. Known history of colitis, pneumonitis and pulmonary fibrosis (for example, inflammatory bowel disease, uncontrolled asthma), which, in the opinion of the 16.Investigator, might impair the subject's tolerance of trial treatment.

Any psychiatric condition that would prohibit the understanding or rendering of informed consent 17.Other invasive malignancy within 2 years except for non-invasive malignancies such as cervical carcinoma in situ, non-melanomatous carcinoma of the skin or ductal carcinoma in situ of the breast that has/have been surgically cured.

Primary outcomes:
measure: Disease Free survival [ Time Frame: 3 years ]
timeFrame: Up to 5 years
Secondary outcomes:
measure: Overall Survival [ Time Frame: 5 years ]
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University
Study officials:
References: