Second-line albumin-bound paclitaxel regimens for advanced gastric or gastroesophageal junction cancer

A Multicenter, Real-world Study on Albumin-bound Paclitaxel-based Second-line Treatment Regimens for Locally Advanced or Metastatic Gastric/Gastroesophageal Junction Adenocarcinoma

This project tries different second-line treatments based on albumin-bound paclitaxel to see which helps people with advanced gastric or gastroesophageal junction cancer whose first-line chemotherapy plus immunotherapy has stopped working.

Quick facts

• Study type: Observational
• Enrollment: 250 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: chemotherapy, radiation, prednisone, immunotherapy, Ramucirumab, trastuzumab, Fruquintinib
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07389876 on ClinicalTrials.gov

What this trial studies

This is an open-label, multi-cohort real-world study that assigns patients to one of five regimens combining albumin-bound paclitaxel alone or with anti-angiogenic agents, immune checkpoint inhibitors, or trastuzumab emtansine. Dosing is given on a 3-week cycle with paclitaxel on days 1 and 8, oral fruquintinib or intravenous ramucirumab used in specified cohorts, PD‑1 inhibitors in immune cohorts, and T‑DM1 for a biomarker-selected group. Eligible patients are adults (18–80) with unresectable locally advanced or metastatic gastric/GJ adenocarcinoma, ECOG 0–2, HER2 negative, no prior taxane, and progression after fluoropyrimidine–platinum plus PD‑1/PD‑L1 therapy. Treatment continues until disease progression or intolerable toxicity, and effectiveness and safety outcomes are collected in a real-world setting.

Who should consider this trial

Good fit: Ideal candidates are adults (18–80) with unresectable locally advanced or metastatic gastric/GJ adenocarcinoma, ECOG 0–2, HER2 negative, with measurable disease who progressed on first-line fluoropyrimidine‑platinum plus PD‑1/PD‑L1 therapy and who have not previously received taxane therapy.

Not a fit: Patients unlikely to benefit include those who previously received taxane therapy, who are HER2 positive (unless eligible for other HER2-directed therapy), or who have poor performance status or very limited expected survival.

Why it matters

Potential benefit: If successful, these regimens could offer better disease control or symptom relief after first-line chemo‑immunotherapy stops working.

How similar studies have performed: Prior second-line trials have shown benefit for taxane-based regimens and for ramucirumab in gastric cancer, and combinations with immune checkpoint inhibitors are biologically promising though less established in this setting.

Eligibility criteria

Inclusion Criteria:

* Fully understand this study and voluntarily sign the informed consent form;
* Between 18 and 80 years old (inclusive), male or female;
* Patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma confirmed by pathology or histology;
* ECOG performance status 0-2;
* Known HER2 negative;
* Expected survival ≥ 3 months;
* Patients who have progressed on first-line systemic treatment with fluoropyrimidine-platinum combination and PD-1/PD-L1 monoclonal antibody, or those who have progressed during maintenance treatment; patients with locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma who have progressed within 6 months after the end of perioperative chemotherapy or adjuvant chemotherapy (counting from the end of the combined regimen);
* Have not received taxane-based therapy previously;
* Have at least one measurable lesion (meeting RECIST v1.1 criteria);
* The functions of important organs meet the following requirements (no blood components or cell growth factors are allowed to be used within 14 days before enrollment):

Absolute neutrophil count ≥ 1.5×109/L, white blood cell count ≥ 3.0×109/L; Platelet count ≥ 90×109/L; Hemoglobin ≥ 8g/dL; Total bilirubin (TBIL) ≤ 1.5×ULN; ALT and AST ≤ 2.5×ULN; BUN and creatinine (Cr) ≤ 1.5×ULN (and creatinine clearance (CCr) ≥ 50mL/min); Left ventricular ejection fraction (LVEF) ≥ 50%; Fridericia-corrected QT interval (QTcF) \< 470 milliseconds; INR ≤ 1.5×ULN, APTT ≤ 1.5×ULN; Thyroid function: TSH ≤ upper limit of normal (ULN). If abnormal, FT3 and FT4 levels should be examined. If FT3 and FT4 levels are normal, the patient can be enrolled; Premenopausal women and postmenopausal women for less than 1 year must have a negative serum or urine pregnancy test before treatment.

Exclusion Criteria:

* Patients with other malignancies within 5 years before enrollment, except for skin basal cell or squamous cell carcinoma after radical surgery, or cervical carcinoma in situ;
* Patients who have received allogeneic bone marrow transplantation or organ transplantation in the past;
* Patients with severe cardiovascular diseases within 6 months before enrollment, including unstable angina or myocardial infarction;
* Patients allergic to the study drug or any of its auxiliary preparations;
* Patients with uncontrolled hypertension before enrollment, defined as systolic blood pressure ≥ 150 mmHg and/or diastolic blood pressure ≥ 90 mmHg;
* Patients with any disease or condition that affects drug absorption before enrollment, or patients who cannot take oral medication;
* Patients with active ulcers in the stomach and duodenum, ulcerative colitis or other digestive tract diseases before enrollment, or unremoved tumors with active bleeding, or other conditions that the investigator deems may cause gastrointestinal bleeding or perforation;
* Patients with obvious bleeding tendency evidence or history within 3 months before enrollment (bleeding \> 30 mL within 3 months, accompanied by hematemesis, melena, or hematochezia), hemoptysis (fresh blood \> 5 mL within 4 weeks), or thromboembolic events (including stroke events and/or transient ischemic attacks) within 12 months;
* Patients with significant clinical cardiovascular diseases, including but not limited to acute myocardial infarction, severe/unstable angina or coronary artery bypass grafting within 6 months before enrollment; congestive heart failure with New York Heart Association (NYHA) classification \> 2; drug-treated ventricular arrhythmias; left ventricular ejection fraction (LVEF) \< 50%;
* Patients with active or uncontrolled severe infections (≥ CTCAE v5.0 grade 2 infections);
* Patients with known human immunodeficiency virus (HIV) infection. Patients with a history of clinically significant liver disease, including viral hepatitis \[known hepatitis B virus (HBV) carriers must exclude active HBV infection, i.e., HBV DNA positive (\> 1×104 copies/mL or \> 2000 IU/mL); known hepatitis C virus (HCV) infection and HCV RNA positive (\> 1×103 copies/mL)\];
* Patients with any active autoimmune disease or a history of autoimmune disease (such as, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism; patients with vitiligo; patients with childhood asthma that has completely resolved and does not require any intervention in adulthood can be included; patients with asthma requiring medical intervention with bronchodilators cannot be included); replacement therapy is not considered systemic treatment, the following patients can be included: those with a history of autoimmune-related hypothyroidism and receiving thyroid hormone replacement therapy; type 1 diabetes that can be controlled with insulin treatment;
* Patients who have used immunosuppressants or systemic hormone therapy to achieve immunosuppression within 7 days before enrollment (dose \> 10 mg/day of prednisone or other equivalent efficacy hormones);
* Patients with interstitial lung disease or pneumonia, pulmonary fibrosis, acute lung disease, or radiation pneumonitis;
* Pregnant (positive pregnancy test before medication) or lactating women; Any other disease, clinically significant metabolic abnormalities, physical examination abnormalities or laboratory test abnormalities, as judged by the investigator, there is reason to suspect that the patient has a disease or condition that is not suitable for the use of the study drug (such as having epilepsy and requiring treatment), or will affect the interpretation of the study results, or put the patient at high risk;
* Patients with urine routine indicating urine protein ≥ 2+ and 24-hour urine protein \> 1.0g;
* Patients deemed unsuitable for inclusion in this study by the investigator.

Where this trial is running

Shanghai, Shanghai Municipality

• Wanjing Feng — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Study coordinator: Wanjing Feng

Conditions Gastric Cancer; Second-line Treatment