Colorectal CancerPhase 2PCOXNCT03638297
PD-1 Antibody Combined With COX Inhibitor in MSI-H/dMMR or High TMB Colorectal Cancer
A Phase 2 study testing PD-1 antibody + cox inhibitor in people with Colorectal Cancer, run by Sun Yat-sen University at 2 sites in China.
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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- PD-1 antibody + cox inhibitor
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 2 sitesChina
- Study dates
- 23 Aug 2018to 31 Aug 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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);
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- 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.
Trial locations and contacts
2 sites in 1 country.
China2 sites, 2 recruiting
- Recruiting
Gastrointestinal Hospital, Sun Yat-sen University
Guangzhou, Guangdong, 510655
Yanghong Deng, PhD, 008613925106525, dengyanh@mail.sysu.edu.cn
Yanhong Deng, PhD
- Recruiting
The Sixth Affiliated Hospital of Sun Yat-sen University
Guangzhou, Guangdong, 510655
Yanhong Deng, M.D., 008613925106525, dengyanh@mail.sysu.edu.cn
About this study
Official title: PD-1 Antibody Combined With COX Inhibitor in MSI-H/dMMR or High TMB Colorectal Cancer: a Single Arm Phase II Study
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.
Read the 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.
- Conditions
- Colorectal Cancer
- Being tested
- PD-1 antibody + cox inhibitor
- Keywords
- MSI-H, dMMR, PD-1 antibody, COX inhibitor, tumor mutation burden
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PD-1 antibody + cox inhibitorDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| PD-1 antibody + cox inhibitor | Experimental | BAT1306 + aspirin(celebrex when there is contraindication to aspirin) on day 1-21 every three weeks Receives: Drug: PD-1 antibody + cox inhibitor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response rate
CR(complete response) + PR (partial response)rate will be assessed according to the RECIST version 1.1 guidelines.
Measured: 6 months
Secondary outcomes (5)
Progression free survival
Time measured from the day of treatment to the date of first documented progression, or death from any cause.
Measured: 2 years
Overall survival time
Estimated from the date of treatment to death from any cause.
Measured: 5 years
disease control rate
CR + PR + SD(stable disease) rate will be assessed according to the RECIST version 1.1 guidelines.
Measured: 6 months
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.
Measured: 2 years
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.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2018
- Study start23 Aug 2018
- Primary completion20 Aug 2022
- Study completion31 Aug 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Sun Yat-sen UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 29 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yanhong Deng, Sun Yat-sen University
- Investigators
- Yanhong Deng, M.D., Principal investigator, Sixth Affiliated Hospital, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03638297
- Sponsor's protocol ID
- GIHSYSU13
- Acronym
- PCOX
- Status last verified
- Oct 2023
- First submitted
- 17 Aug 2018
- Last updated
- 17 Oct 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Wu Z, Zhang Y, Cheng Y, Li J, Li F, Wang C, Shi L, Qin G, Zhan W, Cai Y, Xie X, Ling J, Hu H, Zhang J, Deng Y. PD-1 blockade plus COX inhibitors in dMMR metastatic colorectal cancer: Clinical, genomic, and immunologic analyses from the PCOX trial. Med. 2024 Aug 9;5(8):998-1015.e6. doi: 10.1016/j.medj.2024.05.002. Epub 2024 May 24.
PubMed 38795703
Study at a glance
From the registry record, last updated by the sponsor on 17 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PD-1 Antibody Combined With COX Inhibitor in MSI-H/dMMR or High TMB Colorectal Cancer: a Single Arm Phase II Study
- ClinicalTrials.gov ID
- NCT03638297
- Acronym / sponsor ID
- PCOX / GIHSYSU13
- Conditions
- Colorectal Cancer
- Keywords
- MSI-H, dMMR, PD-1 antibody, COX inhibitor, tumor mutation burden
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 29 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 23 Aug 2018 (actual)
- Primary completion
- 20 Aug 2022 (actual)
- Study completion
- 31 Aug 2025 (estimated)
- First posted
- 20 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PD-1 antibody + cox inhibitor | Experimental | Drug: PD-1 antibody + cox inhibitorBAT1306 + aspirin(celebrex when there is contraindication to aspirin) on day 1-21 every three weeks |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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;
Key exclusion criteria (15 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PD-1 antibody + cox inhibitorBAT1306 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. | Drug | PD-1 antibody + cox inhibitor |
Primary outcome
Response rate
Time frame: 6 months
CR(complete response) + PR (partial response)rate will be assessed according to the RECIST version 1.1 guidelines.
5 secondary outcomes
Progression free survival
Time frame: 2 years
Overall survival time
Time frame: 5 years
disease control rate
Time frame: 6 months
Toxicity assessed using the NCI common toxicity criteria, version 4.0.
Time frame: 2 years
duration of response
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Oct 2023.
- Derived from this study: PubMed 38795703Wu Z, Zhang Y, Cheng Y, Li J, Li F, Wang C, Shi L, Qin G, Zhan W, Cai Y, Xie X, Ling J, Hu H, Zhang J, Deng Y. PD-1 blockade plus COX inhibitors in dMMR metastatic colorectal cancer: Clinical, genomic, and immunologic analyses from the PCOX trial. Med. 2024 Aug 9;5(8):998-1015.e6. doi: 10.1016/j.medj.2024.05.002. Epub 2024 May 24.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yanhong Deng, M.D. principal investigator
Sixth Affiliated Hospital, Sun Yat-sen University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PD-1 antibody + cox inhibitor in people with Colorectal Cancer, run by Sun Yat-sen University at 2 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 17 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Yanhong Deng, M.D. (008613925106525, dengyanh@mail.sysu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response rate (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03638297, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Oct 2023.