A Phase II Clinical Study of PD-1 Inhibitors Combined With Fruquintinib and Chemotherapy in First-line Treatment of HER2-negative Advanced G/GEJ Cancer
Overview
- Phase
- Not Applicable
- Intervention
- Fruquintinib、Nivolumab、Sintilimab、Oxaliplatin、Teysuno、Capecitabine
- Conditions
- Gastric Cancer/Adenocarcinoma of Esophagogastric Junction
- Sponsor
- Fudan University
- Enrollment
- 58
- Locations
- 1
- Primary Endpoint
- PFS
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
This is an open-label, single-arm, single-center clinical study to investigate the safety and efficacy of fuquinitinib combined with PD-1 inhibitors and first-line chemotherapy in the treatment of inoperable HER2-negative advanced GC/GEJC.
Eligible enrolled patients received 6 cycles of combined treatment with fuquinitinib combined with PD-1 inhibitor and chemotherapy (XELOX/SOX) regimen. Maintenance treatment was fuquinitinib combined with PD-1 inhibitor and Teghio/capecitabine until disease progression or toxicity became intolerable. The longest duration of PD-1 inhibitor treatment is 24 months.
Investigators
Xiaodong Zhu
Medical oncology chief physician
Fudan University
Eligibility Criteria
Inclusion Criteria
- •Have fully understood the study and voluntarily signed the informed consent;
- •2.18-80 years old (including 18 and 80 years old), male or female;
- •Patients with unresectable advanced or metastatic gastric/esophagogastric junction adenocarcinoma confirmed by pathology or histology;
- •4.ECOG physical status 0-1
- •Expected survival ≥3 months;
- •Have not received any anti-tumor therapy (including chemotherapy, targeted therapy, immunotherapy, etc.) for unresectable advanced or metastatic gastric cancer; If you have received adjuvant therapy after radical gastrectomy of gastric cancer, it is required that the time between the discovery of metastatic disease and the end of the last adjuvant chemotherapy is greater than 6 months);
- •Must have at least one measurable lesion (meet the RECIST v1.1 standard);
- •The functions of vital organs meet the following requirements (the use of any blood components and cell growth factors is not allowed within the first 14 days of enrollment) :
- •Absolute neutrophil count ≥1.5×109/L, white blood cell ≥3.0×109/L;
- •Platelet ≥90×109/L;
Exclusion Criteria
- •Patients with known HER-2 status (immunohistochemical 3+, or immunohistochemical 2+\&FISH positive);
- •Had other malignancies within 5 years prior to admission, except basal cell or squamous cell carcinoma of the skin after radical surgery, or carcinoma in situ of the cervix;
- •Previously received allogeneic bone marrow transplantation or organ transplantation;
- •Severe cardiovascular disease, including unstable angina pectoris or myocardial infarction, in the 6 months prior to enrollment;
- •Subjects who are allergic to the investigational drug or any of its adjuncts;
- •Hypertension that could not be controlled by drugs before enrollment was defined as: systolic blood pressure ≥150 mmHg and/or diastolic blood pressure ≥90 mmHg;
- •Had any disease or condition affecting drug absorption before enrollment, or the patient could not take drugs orally;
- •Gastrointestinal diseases such as active ulcer of stomach and duodenum, ulcerative colitis, or active bleeding of unexcised tumors, or other conditions that may cause gastrointestinal bleeding or perforation as determined by researchers before enrollment;
- •Patients with evidence or history of significant bleeding tendency within 3 months prior to enrollment (bleeding within 3 months \>30 mL, hematemesis, stool, stool blood), hemoptysis (within 4 weeks \>5 mL of fresh blood) or had a thromboembolic event (including stroke events and/or transient ischemic attacks) within 12 months;
- •Clinically significant cardiovascular disease, including but not limited to acute myocardial infarction, severe/unstable angina pectoris, or coronary artery bypass grafting within 6 months prior to enrollment; New York Heart Association (NYHA) Grades for Congestive Heart Failure \>Level 2; Ventricular arrhythmias requiring medical treatment; LVEF (Left ventricular Ejection Fraction) \<50%;
Arms & Interventions
PD-1 Inhibitors Combined With Fruquintinib and Chemotherapy
Combined treatment period: A total of 6 cycles of combined treatment Fruquintinib: 4 mg/d, qd po, d1-14, q3w. Nivolumab: 360mg iv.gtt d1, q3w or Sindilizumab: 200mg iv.gtt d1, q3w SOX: Oxaliplatin 130mg/m2 iv.gtt d1, Teysuno 40mg/m2 p.o.b.i.d. d1\~ 14q3w. Or XELOX regimen: oxaliplatin 130mg/m2 iv.gtt d1 Capecitabine 1000mg/m2 p.o. b.i.d. d1\~ 14q3w. Maintenance treatment period: Fruquintinib: 4 mg/d, qd po, d1-14, q3w. Nivolumab: 360mg iv.gtt d1, q3w or Sindilizumab: 200mg iv.gtt d1, q3w Teysuno 40mg/m2 p.o.b.i.d. d1\~14 q3w or Capecitabine 1000mg/m2 p.o.b.i.d. d1\~14 q3w. Maintenance of treatment until disease progression or toxicity becomes intolerable.The longest duration of PD-1 inhibitor treatment is 24 months.
Intervention: Fruquintinib、Nivolumab、Sintilimab、Oxaliplatin、Teysuno、Capecitabine
Outcomes
Primary Outcomes
PFS
Time Frame: From date of enrollment until the end of treatment or the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Progression-free survival
Secondary Outcomes
- ORR(From date of enrollment until the end of treatment or the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months)
- OS(From date of enrollment until the end of treatment or the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months)
- DCR(From date of enrollment until the end of treatment or the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months)