Toripalimab With or Without Celecoxib as Neoadjuvant Therapy in Resectable dMMR/MSI-H Colorectal Cancer
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|ClinicalTrials.gov Identifier: NCT03926338|
Recruitment Status : Recruiting
First Posted : April 24, 2019
Last Update Posted : November 5, 2019
Colorectal cancer of Mismatch Repair-deficient (dMMR)/ Microsatellite Instability-high (MSI-H) accounts for approximately 15% of all colorectal cancer patients, with a higher proportion in right colon cancer. Previous studies have found that colon cancer patients with dMMR/MSI-H cannot benefit from 5-fluorouracil (5-FU) adjuvant chemotherapy. Once patients have distant metastases, they are not sensitive to traditional palliative chemotherapy, and the prognosis is significantly worse than that of mismatch repair-proficient (pMMR)/microsatellite stability (MSS). A phase II clinical study of anti-PD-1 immunotherapy based on mismatch repair (MMR) status published in 《N Engl J Med》 showed that the objective response rate (ORR) of advanced colorectal cancer patients with dMMR received anti-PD-1 is 40%, and a longer response time can be obtained compared to conventional chemotherapy.
Anti-PD-1 neoadjuvant therapy has proven to be safe and feasible in lung cancer, bladder cancer and malignant melanoma, and can achieve more than 40% of major pathological response. However, there are no reports of anti-PD-1 neoadjuvant therapy for the dMMR/MSI-H colorectal cancer. Therefore, the aim of this study was to find the best multidisciplinary treatment for resectable colorectal cancer patient with the dMMR/MSI-H phenotype and to explore whether cyclooxygenase (COX) inhibitors combined with anti-PD-1 monoclonal antibody (mAb) could further improve efficacy.
|Condition or disease||Intervention/treatment||Phase|
|Colon Cancer MSI-H||Drug: Neoadjuvant therapy with PD-1 inhibitor plus COX inhibitor Drug: Neoadjuvant therapy with PD-1 inhibitor||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||10 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Study of Toripalimab With or Without Celecoxib as Neoadjuvant Therapy in Resectable Non-metastatic Colorectal Cancer Patients With Mismatch Repair-deficient or Microsatellite Instability-high|
|Actual Study Start Date :||May 10, 2019|
|Estimated Primary Completion Date :||May 1, 2021|
|Estimated Study Completion Date :||May 1, 2022|
Experimental: PD-1 inhibitor plus COX inhibitor
Neoadjuvant therapy with PD-1 inhibitor (Toripalimab) plus COX inhibitor (Celecoxib)
Drug: Neoadjuvant therapy with PD-1 inhibitor plus COX inhibitor
Toripalimab (IV given over 30 min at a dose of 3mg/m2 on day 1, every 2 weeks for 6 cycles) and Celecoxib (oral 200mg once daily for 12 weeks) followed by colectomy
Experimental: PD-1 inhibitor
Neoadjuvant therapy with PD-1 inhibitor (Toripalimab)
Drug: Neoadjuvant therapy with PD-1 inhibitor
Toripalimab (IV given over 30 min at a dose of 3mg/m2 on day 1, every 2 weeks for 6 cycles) followed by colectomy
Other Name: Toripalimab
- Rate of treatment-related surgery delay [ Time Frame: 1 year ]Treatment-related surgery delay was defined as the interval between the last dose of PD-1 inhibitor (Toripalimab) and surgery is more than 28 days.
- Frequency of 3/4 grade adverse events as assessed by common terminology criteria for adverse events (CTCAE) version 5.0 [ Time Frame: 1 year ]Frequency of 3/4 grade adverse events occurring up to 90 days after the last dose of Toripalimab or 30 days after surgery (whichever is longer).
- Down-staging of primary tumors [ Time Frame: 1 year ]Down-staging of the resected tumour as measured by histopathological tumour diameter and stage according to the TNM staging system of American Joint Committee on Cancer (AJCC) (8th version).
- Proportion of patients experiencing major pathological response to neoadjuvant treatment [ Time Frame: 1 year ]The proportion of patients experiencing major pathological response will be computed with associated 95% confidence interval for each treatment arm
- Disease-free survival (DFS) [ Time Frame: 3 years ]Defined as the time from randomization to relapse, metastasis or death from any cause.
- Overall survival (OS) [ Time Frame: 5 years ]Defined as the time from randomization to death from any cause.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03926338
|Contact: Yanhong Deng, M.D.||firstname.lastname@example.org|
|The Sixth Affiliated Hospital of Sun Yat-sen University||Recruiting|
|Guangzhou, Guangdong, China, 510655|
|Contact: Yanhong Deng, M.D. 86-13925106525 email@example.com|
|Principal Investigator:||Yanhong Deng, M.D.||Sixth Affiliated Hospital, Sun Yat-sen University|