A Biomarker Study for Predicting the Efficacy of Neoadjuvant Sintilimab Plus SOX for Gastric Adenocarcinoma.
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ClinicalTrials.gov Identifier: NCT05594381 |
Recruitment Status :
Not yet recruiting
First Posted : October 26, 2022
Last Update Posted : October 26, 2022
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Tracking Information | |||||||||
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First Submitted Date ICMJE | September 29, 2022 | ||||||||
First Posted Date ICMJE | October 26, 2022 | ||||||||
Last Update Posted Date | October 26, 2022 | ||||||||
Estimated Study Start Date ICMJE | October 2022 | ||||||||
Estimated Primary Completion Date | September 2023 (Final data collection date for primary outcome measure) | ||||||||
Current Primary Outcome Measures ICMJE |
Pathological complete response rate (pCR) [ Time Frame: an average of 6 months. ] pCR rate is the proportion of patients who have no residual viable tumor in the resected specimens.
The primary aim of the study is to test the hypothesis that after neoadjuvant therapy,patients with ctDNA clearance result in a higher rate of pCR.
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Original Primary Outcome Measures ICMJE | Same as current | ||||||||
Change History | No Changes Posted | ||||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||||||
Current Other Pre-specified Outcome Measures |
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Original Other Pre-specified Outcome Measures | Same as current | ||||||||
Descriptive Information | |||||||||
Brief Title ICMJE | A Biomarker Study for Predicting the Efficacy of Neoadjuvant Sintilimab Plus SOX for Gastric Adenocarcinoma. | ||||||||
Official Title ICMJE | A Prospective, Open-label, Single-Arm, Phase II Study on Biomarkers for Predicting the Efficacy of Neoadjuvant Sintilimab in Combination With Tegafur and Oxaliplatin (SOX) for cStage III Gastric or Gastroesophageal Junction Adenocarcinoma. | ||||||||
Brief Summary | Recently, a number of clinical studies were carried out to evaluate the therapeutic effects of PD-1 antibodies combined with chemotherapy as preoperative neoadjuvant therapy of gastric cancer (GC) worldwide. Indicators such as PD-L1 expression, TMB and MSI are currently used to evaluate the efficacy of PD-1/PD-L1 monoclonal antibody therapy. However, these biomarkers are mainly used in patients with metastatic and unresectable tumors, and the conclusions obtained in different studies are still partially contradictory, failing to accurately guide the treatment. Therefore, it is urgent to explore highly sensitive and specific biomarkers that can be used to monitor the efficacy of neoadjuvant immunotherapy for GC.The present clinical trial aims to use ctDNA dynamic monitoring combined with multi-omics methods to evaluate PD-1 monoclonal antibody (sintilimab) combined with SOX neoadjuvant therapy for clinical stage III gastric/gastroesophageal junction adenocarcinoma. In order to identify the suitable population for neoadjuvant immunotherapy for locally advanced and resectable G/GEJ adenocarcinoma. | ||||||||
Detailed Description | At present, radical surgery is still the only way to cure Gastric Cancer(GC), but the surgical resection rate is low, and the R0 resection rate is about 70-80%. The postoperative recurrence rate of patients with stage II and above is high. To improve the surgical resection rate, seek more effective treatment. The other treatment therapeutics are the direction of development of GC treatment research. Neoadjuvant therapy for GC can reduce tumor stage and increase the likelihood of complete tumor resection to achieve maximum pathological response. Neoadjuvant chemotherapy followed with surgery has been written into the NCCN guidelines for GC. Since China, the United States and Japan successively approved PD-1 monoclonal antibody for the treatment of unresectable and/or metastatic GC and gastroesophageal junction adenocarcinoma (G/GEJ adenocarcinoma), a number of clinical studies about the therapeutic effects of PD-1 antibodies combined with chemotherapy as preoperative neoadjuvant therapy are carring out worldwide. A single-arm phase II clinical study has demonstrated that the Sintilimab,which is the only one PD-1 mAb that has the indication for first-line treatment of GC in China, combined with oxaliplatin and capecitabine in neoadjuvant treatment of locally advance resectable GC. The treatment showed encouraging pCR rates and a good safety profile. However, how to select suitable patients for neoadjuvant immunotherapy is the focus of current research. Indicators such as PD-L1 expression, tumor mutation burden, and microsatellite stability are currently considered to be the average indicators of the efficacy of PD-1/PD-L1 monoclonal antibody therapy. However, according to the NCCN guidelines, these biomarkers are mainly used in patients with advanced postoperative tumors, and the conclusions obtained in different studies such as KEYNOTE-061 and KEYNOTE-062 are still partially contradictory, failing to accurately guide the treatment. Therefore, it is urgent to explore highly sensitive and specific indicators that can be used to monitor the efficacy of neoadjuvant immunotherapy for GC. This study intends to dynamically detect gene mutations, protein expressions and tumor images in G/GEJ tumor tissues and blood samples before, under and after neoadjuvant therapy by using ctDNA targeted sequencing combined with multi-omics technology. Through independent and association analysis and building risk models, biomarkers with significant predictive effects on the curative effect of neoadjuvant immunotherapy were found, so as to identify the suitable population for neoadjuvant immunotherapy for locally advanced and resectable G/GEJ adenocarcinoma. |
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Study Type ICMJE | Interventional | ||||||||
Study Phase ICMJE | Phase 2 | ||||||||
Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Prevention |
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Condition ICMJE | Gastric Cancer | ||||||||
Intervention ICMJE | Drug: Sintilimab
Neoadjuvant treatment method: Sintilimab 200 mg, i.v., d1 + oxaliplatin 130 mg/m2, d1, i.v., + Tegafur 40 mg po, bid, d1-14; 3-week course; Neoadjuvant therapy: 3 courses of preoperative SOX chemotherapy (oxaliplatin+Tegafur) + PD-1 monoclonal antibody (Sintilimab). After the 2nd and 3rd cycles of neoadjuvant therapy (6-9 weeks from the start of treatment), imaging effects and feasibility of radical surgery were performed respectively; The operation time is arranged within 2-6 weeks after the last administration of neoadjuvant therapy, and the operation method is selected by the surgeon according to the actual needs; The postoperative treatment plan is the same as the preoperative neoadjuvant treatment plan, and the SOX+Sintilimab will continue to be given until the full 8 cycles (including the preoperative 3 cycles). Other Names:
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Study Arms ICMJE | Experimental: Neoadjuvant Sintilimab plus SOX therapy
All enrolled subjects were treated with Sintilimab combined with SOX regimen (Oxaliplatin plus Tegafur) for 3 cycles and then underwent radical surgery. Peripheral blood from all patients will be collected at the following 5 time points: before neoadjuvant therapy (within 3 days before the first dose); before the start of the third cycle of neoadjuvant therapy (within 3 days); before surgery (within 7 days) and after surgery (within 3-7 days). Plasma was tested for ctDNA. All subjects were further stratified according to the detection results of ctDNA and their changes during the neoadjuvant treatment period. After operation, sintilimab combined with SOX therapy was continued for 5 cycles according to the original plan (if the preoperative treatment did not reach 3 cycles, it should be supplemented to 8 cycles) Intervention: Drug: Sintilimab
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Publications * | Not Provided | ||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||||
Recruitment Status ICMJE | Not yet recruiting | ||||||||
Estimated Enrollment ICMJE |
90 | ||||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||||
Estimated Study Completion Date ICMJE | October 2025 | ||||||||
Estimated Primary Completion Date | September 2023 (Final data collection date for primary outcome measure) | ||||||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years to 75 Years (Adult, Older Adult) | ||||||||
Accepts Healthy Volunteers ICMJE | No | ||||||||
Contacts ICMJE |
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Listed Location Countries ICMJE | Not Provided | ||||||||
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Administrative Information | |||||||||
NCT Number ICMJE | NCT05594381 | ||||||||
Other Study ID Numbers ICMJE | JSGCLB-2201 | ||||||||
Has Data Monitoring Committee | Not Provided | ||||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Current Responsible Party | The First Affiliated Hospital with Nanjing Medical University | ||||||||
Original Responsible Party | Same as current | ||||||||
Current Study Sponsor ICMJE | The First Affiliated Hospital with Nanjing Medical University | ||||||||
Original Study Sponsor ICMJE | Same as current | ||||||||
Collaborators ICMJE |
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Investigators ICMJE |
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PRS Account | The First Affiliated Hospital with Nanjing Medical University | ||||||||
Verification Date | October 2022 | ||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |