The Necessity of Surgery in Patients With mGC Achieving Radiological Response After Conversion Therapy (ESMGC)
Phase II Randomized Controlled Trial Evaluating the Necessity of Surgery in Patients With Advanced Metastatic Gastric Cancer Achieving Radiological Response After Conversion Therapy
Study Overview
Status
Conditions
Detailed Description
The innovation and scientific nature of this study lie in its adoption of a multi-center, randomized controlled Phase II study design for the first time. It directly compares the efficacy differences between "surgery + postoperative adjuvant therapy" and "simple continuation of medical treatment" for this specific population, aiming to eliminate selection bias and confirm the causal relationship. We strictly limited the enrolled population to those with "significant imaging remission and technically resectable at R0 level" by MDT assessment, ensuring the homogeneity of the research subjects and the specificity of the questions. The primary research endpoint was set as progression-free survival (PFS), and secondary endpoints included overall survival (OS), R0 resection rate, quality of life (QoL), and treatment-related toxic side effects, allowing for a comprehensive evaluation.
Carrying out this study has significant scientific and clinical value. Its results will provide Level 1 evidence-based medical evidence for the treatment strategy of this population. If the surgical group shows superiority, it will firmly establish the position of surgery and promote it to become the standard treatment; if the results are negative (equivalence between the two groups or the surgical group is inferior), it will avoid a large number of patients suffering from unnecessary surgical trauma, promoting the treatment model to return to a core of systematic treatment, thereby changing global clinical guidelines. At the same time, the study has important health economics significance, helping to allocate limited medical resources to truly benefit patients. Through exploratory research on biological specimens, it can also deepen the understanding of the biological behavior of advanced gastric cancer and provide clues for more precise patient screening in the future.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Xu Dazhi Director of Gastric Surgery Department, Doctoral candidate
- Phone Number: +8618121299796
- Email: xudzh@shca.org.cn
Study Contact Backup
- Name: Yang Han, Doctoral candidate
- Phone Number: +8618121299599
- Email: hanyang0811@163.com
Study Locations
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Shanghai, China, 200032
- Recruiting
- Fudan University Cancer Hospital
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Contact:
- Weijing Zhang
- Phone Number: +86 21 3477 8299
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Age and Informed Consent: The age range is 18 to 75 years (inclusive), and the participant must voluntarily participate in this study and sign the patient informed consent approved by the ethics committee.
- Pathological Diagnosis: Gastric or gastroesophageal junction (GEJ) adenocarcinoma confirmed by histological or cytological examination.
- Disease Staging: Newly diagnosed, unresectable stage IV disease (according to the 8th edition of the AJCC staging system), confirmed by the multidisciplinary team (MDT) of the research center to be unable to undergo radical surgical resection. The types of metastasis include but are not limited to: unresectable distant lymph node metastasis (such as beyond the abdominal aorta trunk, supraclavicular lymph nodes, etc.); distant organ metastasis (such as liver, lungs, peritoneum, ovaries, etc.).
Conversion Therapy and Efficacy:
- Has received 4-6 cycles of first-line standard conversion therapy. The treatment plan should be based on the latest clinical guidelines and molecular typing (such as fluorouracil/platinum double or triple drug chemotherapy, combined with anti-HER2 treatment (for HER2-positive patients) or immune checkpoint inhibitors (PD-1/PD-L1 inhibitors, such as when CPS ≥ 5 or MSI-H, etc.).
- After conversion therapy, according to the RECIST 1.1 standard, confirmed by the independent imaging assessment committee (IRC) or at least two senior radiologists, the efficacy reaches complete response (CR) or partial response (PR).
- Surgical Feasibility Assessment: Re-evaluated by the MDT of the research center (must include senior gastrointestinal surgeons, oncologists, and radiologists), it is considered that all known lesions (primary and metastatic lesions) can be technically achieved R0 resection, and the patient is expected to be safely and tolerably able to undergo surgery.
- Physical Condition: Eastern Cooperative Oncology Group (ECOG) performance status score (PS) of 0 or 1.
Good Organ Function (measured within 14 days before randomization), meeting the following laboratory test value standards:
Hematological System:
Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L Platelet count (PLT) ≥ 100 × 10⁹/L Hemoglobin (Hb) ≥ 90 g/L
Liver Function:
Serum total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN (if liver metastasis, then ≤ 5 × ULN)
- Renal Function:
Serum creatinine (Cr) ≤ 1.5 × ULN, or creatinine clearance rate (Ccr) ≥ 50 mL/min (Cockcroft-Gault formula)
- Female patients of childbearing age must have a negative serum pregnancy test within 7 days before randomization, and all patients (regardless of gender) must agree to take effective contraceptive measures during the study and within 6 months after treatment.
Exclusion Criteria:
- Pathological type: Other pathological types, such as squamous cell carcinoma, adenosquamous carcinoma, undifferentiated carcinoma, gastrointestinal stromal tumor (GIST), etc.
Treatment and efficacy:
- During the conversion therapy, disease progression (PD) was confirmed after assessment.
- Previously received systemic anti-tumor treatment for advanced gastric cancer (except for conversion therapy).
- Previously received radical radiotherapy for the stomach or metastatic lesions.
Surgical contraindications:
- According to MDT assessment, there are residual lesions that cannot be surgically removed (such as diffuse peritoneal metastasis that cannot achieve satisfactory tumor reduction, extensive liver metastasis that cannot preserve sufficient functional liver tissue, etc.).
- There are severe internal medical comorbidities that significantly affect surgical safety, and the anesthesiology and surgical physicians have evaluated that the surgical risk is extremely high, for example:
Uncontrolled heart failure (NYHA cardiac function class III-IV), unstable angina or myocardial infarction within 6 months.
Severe chronic obstructive pulmonary disease (COPD) or other severe respiratory diseases, which are expected to be intolerant to general anesthesia.
Uncontrollable severe infection.
Past and coexisting disease history:
- In the past 5 years, had other active malignant tumors, except for cured skin basal cell carcinoma, cervical carcinoma in situ, etc.
- Had any uncontrolled severe clinical problems (such as severe mental or neurological diseases) that affected the compliance with the protocol or interfered with the interpretation of the research results.
- Laboratory test abnormalities: Any serious and uncontrolled laboratory test abnormalities were found. The investigator considered that participating in this study would bring significant risks.
- Pregnancy and lactation: Pregnant or lactating women.
- Other: Known to have a severe allergic history to any drugs (chemotherapy drugs, targeted drugs, immunotherapies, anesthetics, etc.) used in the study protocol. The investigator believed that there were any other situations that were not suitable for participating in this clinical study.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
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Experimental: The surgical group
Surgical radical resection (primary lesion + metastatic lesion) + postoperative adjuvant therapy
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Surgical radical resection (primary lesion + metastatic lesion)
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Experimental: The non-surgical group
Without surgery, continue with the original medical treatment plan until the disease progresses or intolerable toxicity occurs.
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Without surgery, continue with the original medical treatment plan until the disease progresses or intolerable toxicity occurs.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
2-year PFS
Time Frame: 2 year
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Two-year progression-free survival rate
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2 year
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
2-year OS
Time Frame: 2 year
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2 year Overall Survival
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2 year
|
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The R0 resection rate
Time Frame: 2 year
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The R0 resection rate of surgery group
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2 year
|
Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
- Janjigian YY, Shitara K, Moehler M, Garrido M, Salman P, Shen L, Wyrwicz L, Yamaguchi K, Skoczylas T, Campos Bragagnoli A, Liu T, Schenker M, Yanez P, Tehfe M, Kowalyszyn R, Karamouzis MV, Bruges R, Zander T, Pazo-Cid R, Hitre E, Feeney K, Cleary JM, Poulart V, Cullen D, Lei M, Xiao H, Kondo K, Li M, Ajani JA. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet. 2021 Jul 3;398(10294):27-40. doi: 10.1016/S0140-6736(21)00797-2. Epub 2021 Jun 5.
- Smyth EC, Nilsson M, Grabsch HI, van Grieken NC, Lordick F. Gastric cancer. Lancet. 2020 Aug 29;396(10251):635-648. doi: 10.1016/S0140-6736(20)31288-5.
- Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Ruschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. doi: 10.1016/S0140-6736(10)61121-X. Epub 2010 Aug 19.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- ESMGC
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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