Nimotuzumab Combined With Paclitaxel as Second-line Treatment for Recurrent Metastatic Gastric or Esophagogastric Junction Adenocarcinoma With EGFR Over-expression: A Randomized, Double-blind, Placebo-controlled Phase III Clinical Trial
In order to evaluate the efficacy and safety of nimotuzumab combined with paclitaxel as second-line treatment for recurrent metastatic gastric or esophagogastric junction adenocarcinoma with EGFR over-expression, investigators performed a randomized, double-blind, placebo-controlled phase III clinical trial. Patients will be randomized (1:1) to receive nimotuzumab plus paclitaxel in the experimental group and placebo plus paclitaxel in the control group. The primary endpoint of this study was OS, and according to the results of the RAINBOW-Asia gastric cancer phase III clinical study, the mOS of paclitaxel single-agent second-line treatment for gastric cancer was 7.92 months, assuming that the mOS increased to 10.92 months after the addition of nimotuzumab, Using the survival module in the PASS15 software, the two-sided test level was set α=0.05, β=0.20, enrolled for 2 years, followed up for 1.5 years, the dropout rate was 5%, the sample size including interim analysis was 354 cases. The secondary endpoints are progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), disease control rate (DCR), patient reported outcome (PRO), and safety.
• 1\. Age: 18-75 years old (including boundary value), male or female;
• 2\. The physical status score ECOG is 0-1;
• 3\. Histopathologically or cytologically confirmed gastric or esophagogastric junction adenocarcinoma;
• 4\. Recurrent metastatic disease, previous treatment with first-line standard chemotherapy regimens (including platinum-containing and/or fluorouracil regimens) (recurrence or metastasis during adjuvant therapy or within 6 months after completion is considered first-line therapy), or received anti-HER2 therapy, or received immunotherapy, and has been confirmed by the investigator or has a clear disease progression in the medical history;
• 5\. At least one evaluable tumor lesion according to the RECIST version 1.1 evaluation criteria;
• 6\. Detection of primary or metastatic lesions during the screening period (when multiple specimens exist at the same time, the bulk specimen is preferred over the biopsy specimen, and the metastasis is preferred over the primary lesion) tissue is determined to be EGFR high expression (IHC2+ or IHC3+);
• 7\. Estimated survival≥ 12 weeks;
• 8\. Have proper organ function, defined as:Total bilirubin ≤ 1.5 times the upper normal limit (ULN); glutamyltransferase (ALT) or aspartate aminotransferase (AST) ≤ 2.5 times ULN in the absence of liver metastases; ALT or AST ≤ 5 times ULN in the presence of liver metastases;Serum creatinine level≤ 1.5 times ULN; neutrophil count ≥1.5×109/L; WBC count≥ 3.0×109/L; platelets≥ 100×109/L; Hemoglobin≥ 90g/L;
• 9\. Patients of childbearing age and their spouses are willing to use contraception;
• 10\. Women of potential fertility have negative serum hCG within 72 hours prior to randomization (postmenopausal women with amenorrhea for at least 12 months are considered infertile, and women who are known to have undergone tubal ligation are not required to undergo a pregnancy test);
• 11\. The subject understands and complies with the study process, voluntarily participates, and signs the informed consent form.