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Chemotherapy Combined With Apatinib and PD-1 Antibody

Phase 2
Completed
Conditions
Gastric Cancer
Interventions
Drug: PD-1 antibody, paclitaxel or irinotecan, Apatinib mesylate
Registration Number
NCT05025033
Lead Sponsor
Tianjin Medical University Cancer Institute and Hospital
Brief Summary

The effective rate of second-line and later-line single-agent therapy for advanced gastric cancer is limited. This research plan aims to explore whether the combination of drugs can further improve the benefits of second-line and above therapies. Previous studies have shown that there is a significant synergistic effect between chemotherapy and PD-1 monoclonal antibody, or anti-angiogenic TKI drugs and PD-1 monoclonal antibody. This project is planned to be based on the classic chemotherapy drugs irinotecan or paclitaxel, combined with mesylate Apatinib and PD-1 monoclonal antibody, explore the effectiveness and safety of this three-drug combination regimen for the second-line and above treatment of advanced gastric cancer, in order to provide a better late-line treatment plan for patients with advanced gastric cancer.

Detailed Description

This study is a prospective, single-center, single-arm phase II clinical study, which aims to explore the efficacy of PD-1 antibody combined with apatinib combined with chemotherapy as a second-line and above regimen in the treatment of advanced gastric cancer.The enrolled patients were patients with advanced inoperable gastric cancer or gastroesophageal junction adenocarcinoma who had advanced first-line fluorouracil combined with platinum or advanced second-line paclitaxel and irinotecan, with an ECOG PS of 0-1. Treatment plan: PD-1 antibody: 200mg intravenous drip every 3 weeks; Apatinib 250mg/day; Chemotherapy: Irinotecan 150mg/m2, intravenous drip every 2 weeks, or Paclitaxel 150mg/m2, intravenous drip, once every 3 weeks. An imaging evaluation is performed every 6-8 weeks. Monitor blood routine, blood biochemistry, electrocardiogram, urine routine, thyroid function, heart function according to clinical routine, and record adverse events. Primary observational endpoints: objective effective rate (ORR), progression-free survival time (PFS), secondary observational endpoints: overall survival time (OS), disease control rate (DCR) and safety, and dynamic monitoring of serum biomolecular markers for exploration study .

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
30
Inclusion Criteria

Patient age ≥18 years old;

  1. The ECOG score is 0-1 points;
  2. Patients with locally advanced gastric cancer or GEJ adenocarcinoma who have been histologically confirmed, metastatic or unresectable;
  3. Have received at least one systemic chemotherapy regimen in the past and have progressed; or have received adjuvant chemotherapy, but the disease has progressed or relapsed within 6 months after the end of the treatment; have not used any of the drug treatments in this study;
  4. There are measurable lesions that meet the RECIST 1.1 standard;
  5. It has sufficient organ and bone marrow function, and the laboratory examination meets the following requirements: a.HGB≥90g/L;b.NEUT≥1.5×109/L;c.PLT ≥100×109/L;d. BIL≤1.5 times the upper limit of normal (ULN);e. ALT and AST≤2.5×ULN; liver metastasis, then ALT and AST≤5×ULN;f. Endogenous creatinine clearance rate ≥50ml/min (Cockcroft-Gault formula);g. Urine routine is normal, or urine protein <(++), or 24-hour urine protein <1.0 g;
  6. Normal blood coagulation, no active bleeding and thrombosis: a. International normalized ratio INR≤1.5;b. Partial thromboplastin time APTT≤1.5 ULN;
  7. Women of childbearing age must undergo a negative pregnancy test (serum or urine) within 14 days before enrollment, and voluntarily use appropriate methods of contraception during the observation period and within 8 weeks after the last administration of the study drug; for men, it should be surgery Sterilize or agree to use appropriate methods of contraception during the observation period and within 8 weeks after the last administration of the study drug;
  8. Estimated survival period ≥ 3 months;
  9. The patient voluntarily joined the study and signed an informed consent form (ICF);Those who are expected to have good compliance can follow up the efficacy and adverse reactions as required by the protocol.
Exclusion Criteria
  1. Have received anti-angiogenesis drug therapy in the past;
  2. Have received anti-PD-1 and anti-PD-L1 antibody drug therapy in the past;
  3. Patients with high blood pressure who cannot be reduced to the normal range by antihypertensive drugs (systolic blood pressure>140 mmHg, diastolic blood pressure>90 mmHg), coronary heart disease above grade I, grade I arrhythmia (including QTc interval prolongation) Male>450 ms, female>470 ms) and grade I cardiac insufficiency;
  4. There are many factors that affect oral drugs (such as inability to swallow and intestinal obstruction, etc.);
  5. Allergic to the drugs in this program;
  6. Patients with a clear gastrointestinal bleeding tendency, including the following conditions: local active ulcer lesions, and fecal occult blood (+ +) cannot be included in the group; patients with a history of melena and hematemesis within 1 month;
  7. Patients with contraindications to apatinib: For patients with active bleeding, intestinal perforation, intestinal obstruction, within 30 days after major surgery, drug-uncontrollable hypertension, grade Ⅲ-Ⅳ cardiac insufficiency (NYHA standard), severe liver and kidney Patients with dysfunction (Grade 4); If you have immune system diseases, you need to use a daily dose of dexamethasone above 10mg;
  8. According to the judgment of the investigator, patients with concomitant diseases that seriously endanger the safety of the patient or affect the completion of the study;
  9. The researcher believes that it is not suitable for inclusion.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
PD-1 antibody combined with apatinib and chemotherapyPD-1 antibody, paclitaxel or irinotecan, Apatinib mesylatePD-1 antibody: 200mg intravenous drip every 3 weeks; Apatinib: 250mg/day; Chemotherapy: Irinotecan: 150mg/m2, intravenous drip every 2 weeks, or Paclitaxel: 150mg/m2, intravenous drip once every 3 weeks.
Primary Outcome Measures
NameTimeMethod
The Overall Response RateFrom date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months

The proportion of CR and PR

Progression Free SurvivalFrom date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months

Time from the start of treatment to the progression of the disease

Secondary Outcome Measures
NameTimeMethod
Overall survivalFrom date of randomization until the date of death from any cause or the last visit date, whichever came first, assessed up to 60 months

Time from the start of treatment to the occurrence of death

Disease Control rateFrom date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months

The proportion of CR,PR and SD

adverse eventsUntil 3 months after the end of the treatment

The incidence of various adverse events

Trial Locations

Locations (1)

Tianjin Medical University Cancer Institute and Hospital

🇨🇳

Tianjin, Tianjin, China

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