PCOX: PD-1 Antibody Combined With COX Inhibitor in MSI-H/dMMR or High TMB Colorectal Cancer
Study Details
Study Description
Brief 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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2 |
Detailed 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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: PD-1 antibody + cox inhibitor BAT1306 + aspirin(celebrex when there is contraindication to aspirin) on day 1-21 every three weeks |
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.
|
Outcome Measures
Primary Outcome Measures
- Response rate [6 months]
CR(complete response) + PR (partial response)rate will be assessed according to the RECIST version 1.1 guidelines.
Secondary Outcome Measures
- Progression free survival [2 years]
Time measured from the day of treatment to the date of first documented progression, or death from any cause.
- Overall survival time [5 years]
Estimated from the date of treatment to death from any cause.
- disease control rate [6 months]
CR + PR + SD(stable disease) rate will be assessed according to the RECIST version 1.1 guidelines.
- Toxicity assessed using the NCI common toxicity criteria, version 4.0. [2 years]
The grade of toxicity will be assessed using the NCI common toxicity criteria, version 4.0.
- duration of response [2 years]
Time measured from the day of first documented PR or CR to the date of first documented progression, or death from any cause.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Signed informed consent; able to comply with study and/or follow- up procedures;
-
Age:18-75 years old;
-
Histological or cytological documentation of colorectal cancer;
-
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
-
There must be documentation by CT scan, MRI, or intraoperative palpation that tumor is unresectable;
-
Have had at least one lines of chemotherapy fail or refuse to receive chemotherapy;
-
Histologically confirmed metastatic or primary colorectal cancer as dMMR/MSI-H or whole exon sequence confirmed tumor mutation burden higher than 1000;
-
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:
-
Previous treatment with other therapy targeting T-cell costimulation or immune checkpoint pathways;
-
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);
-
A previous cancer active within the previous 5 years;
-
Subjects with known allergy to the study drugs or to any of its excipients;
-
Significant cardiovascular disease including unstable angina or myocardial infarction within 6 months before initiating study treatment;
-
Heart failure grade III/IV (NYHA-classification);
-
Patients with active infection within 1 week before enrollment (infection caused by fever above 38 °C);
-
Patients with severe lung disease (interstitial pneumonia, pulmonary fibrosis, severe emphysema);
-
Patients with active gastrointestinal bleeding;
-
Patients with serious complications (intestinal obstruction, renal insufficiency, hepatic insufficiency, cerebrovascular disorders);
-
Psychiatric disease or a history of central nervous system disease that affects clinical treatment;
-
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;
-
Breast- feeding or pregnant women;
-
Lack of effective contraception;
-
The investigator determined that the patient was not eligible for this clinical trial.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Gastrointestinal Hospital, Sun Yat-sen University | Guangzhou | Guangdong | China | 510655 |
2 | The Sixth Affiliated Hospital of Sun Yat-sen University | Guangzhou | Guangdong | China | 510655 |
Sponsors and Collaborators
- Sun Yat-sen University
Investigators
- Principal Investigator: Yanhong Deng, M.D., Sixth Affiliated Hospital, Sun Yat-sen University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GIHSYSU13