Nimotuzumab and Paclitaxel for Advanced Gastric Cancer

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

This study is testing if a combination of nimotuzumab and paclitaxel can help people with advanced gastric cancer live longer compared to a placebo treatment.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 354 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Biotech Pharmaceutical Co., Ltd. (other)
• Drugs / interventions: chemotherapy, immunotherapy, nimotuzumab, nilotuzumab
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT05978050 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness and safety of nimotuzumab combined with paclitaxel as a second-line treatment for patients with recurrent metastatic gastric or esophagogastric junction adenocarcinoma that over-expresses EGFR. The study is designed as a randomized, double-blind, placebo-controlled phase III trial, enrolling 354 patients who will be assigned to receive either the combination treatment or a placebo with paclitaxel. The primary goal is to assess overall survival, with treatment continuing until disease progression or intolerable side effects occur. Patients will be monitored for a total of 1.5 years after enrollment.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with recurrent metastatic gastric or esophagogastric junction adenocarcinoma and EGFR over-expression.

Not a fit: Patients with non-recurrent gastric cancer or those who do not express EGFR may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve overall survival rates for patients with advanced gastric cancer.

How similar studies have performed: Previous studies have shown promising results with similar combinations of targeted therapies and chemotherapy in treating gastric cancer.

Eligibility criteria

Inclusion Criteria:

* 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.

Exclusion Criteria:

* 1\. Received the following treatments before this study:

  1. The disease has progressed after previous paclitaxel chemotherapy or molecular targeted drug (anti-EGFR antibody) treatment, or received paclitaxel chemotherapy or molecular targeted drug (anti-EGFR antibody) treatment within 4 weeks before randomization;
  2. Within 4 weeks before randomization or participating in other therapeutic/intervention clinical trials or receiving combined treatment prohibited by the protocol;
* 2\. Received major surgical treatment, incision biopsy (such as laparotomy) or obvious traumatic injury within 4 weeks before randomization;
* 3\. Brain metastases or meningeal metastases;
* 4\. Has a history of malignant tumors other than gastric adenocarcinoma or esophagogastric junction adenocarcinoma (except for cured cervical carcinoma in situ or skin basal cell carcinoma and other malignant tumors that have been cured for 5 years);
* 5\. Known to have suffered from severe bleeding disorders (such as severe gastrointestinal bleeding) and vasculitis within 3 months before randomization;
* 6\. Known to be accompanied by other serious diseases, including but not limited to:

  1. Refractory congestive heart failure (NYHA classification III or IV, see Appendix 2), unstable angina, poorly controlled arrhythmia, uncontrolled moderate or high blood pressure (SBP\>160mmHg or DBP\>100mmHg );
  2. Uncontrolled diabetes;
  3. Mental illness that affects informed consent and/or protocol compliance;
  4. There are serious diseases that other researchers believe are not suitable for participating in this study;
* 7\. Known allergies or contraindications to anti-EGFR antibody preparations, paclitaxel and other components;
* 8\. Patients who have previously used immune checkpoint inhibitors (such as anti-PD-1, anti-PD-L1, anti-CTLA-4 antibodies), such as the following adverse events related to immune checkpoint inhibitors and have not recovered to grade 1 And below, not suitable for inclusion: Grade ≥3 ocular adverse events, abnormal liver function in line with Hy's Law standard adverse events, ≥3 neurological toxicity, ≥3 grade colitis, ≥3 grade renal toxicity;
* 9\. Those who are known to have third space effusion (including a large amount of pleural effusion or ascites) that cannot be controlled by drainage or other methods;
* 10\. Known NCI CTC grade 2-4 peripheral neuropathy;
* 11\. Known history of primary or secondary immunodeficiency or current active primary or secondary immunodeficiency;
* 12\. Patients with untreated chronic hepatitis B or chronic hepatitis B virus (HBV) DNA ≥ 1000 IU/ml or hepatitis C virus (HCV) RNA positive (inactive hepatitis B surface antigen carriers, treated And stable hepatitis B patients \[HBV DNA \<1000 IU/ml and cured hepatitis C patients can be selected\]); Treponema pallidum antibody positive or human immunodeficiency virus antibody positive or any uncontrolled infection By;
* 13\. Women of childbearing age who are pregnant, breast-feeding, planning to become pregnant, or who have not taken reliable birth control measures and men in the sexually active period who are unwilling to take birth control measures during the study period and within 3 months after the last medication, and during the above-mentioned specified time Sperm donors;
* 14\. Any medical, psychiatric or other condition or situation that the investigator believes that the subject's participation in this clinical research may have a negative impact on the safety of the subject or the reliability of the research data.

Where this trial is running

Guangzhou, Guangdong

• National Sun Yat-sen University Cancer Center — Guangzhou, Guangdong, China (RECRUITING)

Study contacts

• Principal investigator: ruihua Xu, Doctor — Sun Yat-sen University
• Study coordinator: xijuan Song

Conditions: Gastric or Esophagogastric Junction Adenocarcinoma