Toripalimab Plus FLOT in Locally Advanced Gastric Cancer
Study Details
Study Description
Brief Summary
Neoadjuvant therapy for locally advanced gastric cancer is still in the exploratory stage. With the emergence of immune checkpoint inhibitors, neoadjuvant chemoimmunotherapy is also in the exploratory stage in locally advanced gastric cancer. At present, chemotherapy combined with immunotherapy is usually a simple combination of chemotherapeutic drugs and immune drugs, without taking into account of the influenece of applied sequence. The purpose of this study is to explore whether the sequence of chemotherapy and immunotherapy influence the complete pathological response rate in locally advanced gastric cancer.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
Neoadjuvant therapy for locally advanced gastric cancer is still in the exploratory stage. With the emergence of immune checkpoint inhibitors, neoadjuvant chemoimmunotherapy is also in the exploratory stage in locally advanced gastric cancer. At present, chemotherapy combined with immunotherapy is usually a simple combination of chemotherapeutic drugs and immune drugs, without taking into account of the influenece of applied sequence. The purpose of this study is to explore whether the sequence of chemotherapy and immunotherapy influence the complete pathological response rate in locally advanced gastric cancer. All patients received toripalimab plus FLOT regimen. If pCR was achieved, the patients received two cycles of toripalimab plus FLOT, then toripalimab maintenance until one year, if pCR was not achieved, the patients received 8 cycles of perioperative toripalimab plus FLOT, then toripalimab maintenance until one year.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: experimental group patients received FLOT regimen on day 1 and toripalimab on day 3. |
Drug: delayed toripalimab
chemotherapy plus toripalimab and toripalimab was delayed on day 3. If the pCR was not achieved after surgery, then the patients received five cycles of FLOT plus toripalimab every two weeks, then toripalimab maintenance until one year. If pCR was achieved, then then the patients received two cycles of original regimen and then toripalimab maintenance until one year.
Other Names:
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| Other: control group patients received FLOT regimen and toripalimab on day 1. |
Drug: control
chemotherapy and toripalimab were given on same day. If the pCR was not achieved after surgery, then the patients received four cycles of FLOT plus toripalimab every two weeks, then toripalimab maintenance until one year. If pCR was achieved, then then the patients received two cycles of original regimen and then toripalimab maintenance until one year.
Other Names:
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Outcome Measures
Primary Outcome Measures
- pathological complete response rate [6 months]
the proportion of patients with no tumor cells in the postoperative specimens
Secondary Outcome Measures
- rate of adverse events [3 months]
rate of adverse events
- disease-free survival [3 years]
the rate of patients who keep from disease at three years
Eligibility Criteria
Criteria
Inclusion Criteria:
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70 ≥ Age ≥ 18 years regardless of gender
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Gastric adenocarcinoma confirmed by pathology
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no distant metastasis and resectable or potentially resectable evaluated by general surgery experts
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ECOG PS 0-1
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clinical stage III by AJCC 8.0
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expected lifespan over 3 months
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Adequate organ function: 1) without growth factor and blood component support in the first 2 weeks of enrollment; 2) Cardiac function: no heart disease or coronary heart disease, grade 1-2; 3) liver function: TBIL ≤ 2ULN, AST ≤ 2.5 ULN, alt ≤ 2.5 ULNX 4 Renal function: cr ≤ 1.25ULN, liver function: TBIL ≤ 2ULN, TBIL ≤ 2.5ULN, alt ≤ 2.5ULN, 4)renal function: cr ≤ 1.25ULN.
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blood pressure normal or controlled within the normal range by antihypertensive drugs
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Diabetic patients were treated with hypoglycemic drugs to control fasting blood glucose ≤ 8mmol/L
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Patients with positive hepatitis B surface antigen need to be tested for quantitative detection of hepatitis B DNA virus. HBV DNA should be less than the upper limit of the normal test value for patients with HBV infection.
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no other serious diseases conflicting with this study
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No history of other malignant tumors
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Women of childbearing age must be tested negative for blood pregnancy test within 7 days before enrollment, and subjects of childbearing age must use appropriate contraceptive measures during the trial and within 6 months after the trial
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agreement to participate in this study and signed the informed consent form
Exclusion Criteria:
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Pregnant or lactating women
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Suffered from severe infectious diseases within 4 weeks before entering the group
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Bronchial asthma requires intermittent use of bronchodilators or medical intervention
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Due to the use of immunosuppressants before coexisting diseases and the dosage of immunosuppressants ≥ 10mg/, the oral dose of prednisone lasted for more than 2 weeks
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Clinically obvious cardio-cerebrovascular diseases, including, but not limited to, severe acute myocardial infarction, instability or severe angina pectoris, coronary artery bypass surgery, congestive heart failure, ventricular arrhythmias requiring medical intervention, left ventricular ejection fraction < 50%, stroke within 6 months
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Allergic to any experimental drug and its excipients, or have a history of severe allergy, or are contraindications to experimental drugs
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Severe mental disorders
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Abnormal coagulation function (PT > 16s, APTT > 53s, TT > 21s Fib < 1.5g/L), bleeding tendency or undergoing thrombolysis or anticoagulation therapy
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Past or present pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, severe impairment of lung function, etc.
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Unable to swallow research drugs, chronic diarrhea (including but not limited to irritable bowel syndrome, Crohn's disease, ulcerative colitis) and intestinal obstruction affect drug use and absorption
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Have a history of immunodeficiency, including positive for HIV, or suffer from other acquired, congenital immunodeficiency diseases, or have a history of organ transplant
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Other researchers evaluate those who do not meet the criteria for admission
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital | Zhengzhou | Henan | China | 450008 |
Sponsors and Collaborators
- Henan Cancer Hospital
Investigators
- Principal Investigator: Quanli Gao, M.D, Department of Immunotherapy, Henan Provincial Cancer Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
- He X, Du Y, Wang Z, Wang X, Duan J, Wan R, Xu J, Zhang P, Wang D, Tian Y, Han J, Fei K, Bai H, Tian J, Wang J. Upfront dose-reduced chemotherapy synergizes with immunotherapy to optimize chemoimmunotherapy in squamous cell lung carcinoma. J Immunother Cancer. 2020 Oct;8(2). pii: e000807. doi: 10.1136/jitc-2020-000807.
- Loibl S, Untch M, Burchardi N, Huober J, Sinn BV, Blohmer JU, Grischke EM, Furlanetto J, Tesch H, Hanusch C, Engels K, Rezai M, Jackisch C, Schmitt WD, von Minckwitz G, Thomalla J, Kümmel S, Rautenberg B, Fasching PA, Weber K, Rhiem K, Denkert C, Schneeweiss A. A randomised phase II study investigating durvalumab in addition to an anthracycline taxane-based neoadjuvant therapy in early triple-negative breast cancer: clinical results and biomarker analysis of GeparNuevo study. Ann Oncol. 2019 Aug 1;30(8):1279-1288. doi: 10.1093/annonc/mdz158. Erratum in: Ann Oncol. 2022 Jul;33(7):743-744.
- Voorwerk L, Slagter M, Horlings HM, Sikorska K, van de Vijver KK, de Maaker M, Nederlof I, Kluin RJC, Warren S, Ong S, Wiersma TG, Russell NS, Lalezari F, Schouten PC, Bakker NAM, Ketelaars SLC, Peters D, Lange CAH, van Werkhoven E, van Tinteren H, Mandjes IAM, Kemper I, Onderwater S, Chalabi M, Wilgenhof S, Haanen JBAG, Salgado R, de Visser KE, Sonke GS, Wessels LFA, Linn SC, Schumacher TN, Blank CU, Kok M. Immune induction strategies in metastatic triple-negative breast cancer to enhance the sensitivity to PD-1 blockade: the TONIC trial. Nat Med. 2019 Jun;25(6):920-928. doi: 10.1038/s41591-019-0432-4. Epub 2019 May 13. Erratum in: Nat Med. 2019 Jun 17;:.
- HenanCH immunotherapy006