PD-1 Antibody Combined With COX Inhibitor in MSI-H/dMMR or High TMB Colorectal Cancer

Colorectal Cancer Clinical Trial

— PCOX  

Official title:

PD-1 Antibody Combined With COX Inhibitor in MSI-H/dMMR or High TMB Colorectal Cancer: a Single Arm Phase II Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03638297
• Other study ID #: GIHSYSU13
• Status: Recruiting
• Phase: Phase 2
• Start date: August 23, 2018
• Est. completion date: August 31, 2025

Study information

• Verified date: October 2023
• Source: Sun Yat-sen University
• Contact: Yanhong Deng, M.D.
• Phone: 008613925106525
• Email: dengyanh[@]mail.sysu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

PD-1(programmed death protein 1)antibody has been to approved in patients with MSI-H/dMMR advanced cancer and has achieved significant efficacy. It is reported that the objective response rate of Pembrolizumab and Nivolumab are 40% and 31.1% in MSI-H/dMMR (microsatellite instability-high/deficiency mismatch repair )colorectal cancer. What's more, most of the patients who had response for PD-1 antibody achieved a long duration of disease control. However, not all patients with MSI-H/dMMR was sensitive to PD-1 antibody despite it is a biomarker for PD-1 antibody treatment. There were about 50-60% of patients with MSI-H/dMMR were insensitive and we don't know why. What's more, it's reported that tumor mutation burden (TMB) may be another biomarker of response to PD-1 therapy. COX (cyclooxygenase)inhibitor has been proved to prevent adenomas in colorectal and it is safe for most of the patients. Preclinical models also showed that COX inhibitor could act with PD-1 antibody in mice and control disease progress. So, this study aims to evaluated efficacy and safety of combination of PD-1 antibody and COX inhibitor in patients with MSI-H/dMMR or high tumor mutation burden colorectal cancer.

Description:

This is a single arm, phase two study. Eligible patients with advanced MSI-H/dMMR colorectal cancer were assigned to receive BAT1306 plus COX inhibitor. All patients will receive the study regimen every 3 weeks. Chest/abdomen/pelvic CT with IV contrast will be performed to assess clinical response.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 29
• Est. completion date: August 31, 2025
• Est. primary completion date: August 20, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Signed informed consent; able to comply with study and/or follow- up procedures;

2. Age:18-75 years old;

3. Histological or cytological documentation of colorectal cancer;

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;

5. There must be documentation by CT scan, MRI, or intraoperative palpation that tumor is unresectable;

6. Have had at least one lines of chemotherapy fail or refuse to receive chemotherapy;

7. Histologically confirmed metastatic or primary colorectal cancer as dMMR/MSI-H or whole exon sequence confirmed tumor mutation burden higher than 1000;

8. Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment: Hemoglobin (Hb) = 90g/ L, absolute neutrophil count (ANC) = 1.5×109/ L, platelet count = 100×109/ L; Total bilirubin = 1.5×the upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 5 ×ULN; Serum creatinine =1.5×the ULN.

Exclusion Criteria:

1. Previous treatment with other therapy targeting T-cell costimulation or immune checkpoint pathways;

2. Active, known, or suspected autoimmune disease (except for type 1 diabetes mellitus, residual hypothyroidism due to autoimmune condition requiring only hormone replacement, or conditions not expected to recur in the absence of an external trigger);

3. A previous cancer active within the previous 5 years;

4. Subjects with known allergy to the study drugs or to any of its excipients;

5. Significant cardiovascular disease including unstable angina or myocardial infarction within 6 months before initiating study treatment;

6. Heart failure grade III/IV (NYHA-classification);

7. Patients with active infection within 1 week before enrollment (infection caused by fever above 38 °C);

8. Patients with severe lung disease (interstitial pneumonia, pulmonary fibrosis, severe emphysema);

9. Patients with active gastrointestinal bleeding;

10. Patients with serious complications (intestinal obstruction, renal insufficiency, hepatic insufficiency, cerebrovascular disorders);

11. Psychiatric disease or a history of central nervous system disease that affects clinical treatment;

12. Receive other anti-tumor treatments (including anti-tumor immunotherapy, interventional therapy and intra-serosal injection of anti-tumor drugs) or participate in other interventional clinical trials within two weeks before enrollment;

13. Breast- feeding or pregnant women;

14. Lack of effective contraception;

15. The investigator determined that the patient was not eligible for this clinical trial.

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Drug:
• PD-1 antibody + cox inhibitor
BAT1306 100mg /pembrolizumab 200mg on day 1 + aspirin 200mg oral (celebrex 400mg oral when there is contraindication to aspirin) on day 1-21 every three weeks Contraindication to aspirin : Allergic or intolerance to aspirin; With peptic ulcers; With hemophilia or other bleeding tendencies; Have the gentic disease glucose-6 phosphate dehydrogenase deficiency.

Locations

Country	Name	City	State
China	Gastrointestinal Hospital, Sun Yat-sen University	Guangzhou	Guangdong
China	The Sixth Affiliated Hospital of Sun Yat-sen University	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate	CR(complete response) + PR (partial response)rate will be assessed according to the RECIST version 1.1 guidelines.	6 months
Secondary	Progression free survival	Time measured from the day of treatment to the date of first documented progression, or death from any cause.	2 years
Secondary	Overall survival time	Estimated from the date of treatment to death from any cause.	5 years
Secondary	disease control rate	CR + PR + SD(stable disease) rate will be assessed according to the RECIST version 1.1 guidelines.	6 months
Secondary	Toxicity assessed using the NCI common toxicity criteria, version 4.0.	The grade of toxicity will be assessed using the NCI common toxicity criteria, version 4.0.	2 years
Secondary	duration of response	Time measured from the day of first documented PR or CR to the date of first documented progression, or death from any cause.	2 years