Clinical trial NCT05025033: Chemotherapy Combined With Apatinib and PD-1 Antibody
Official title: Chemotherapy Combined With Apatinib and PD-1 Monoclonal Antibody for Second-line or Above Treatment of Advanced Gastric Cancer-A Prospective, Single-arm, Open, Phase II Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gastric Cancer
Keywords: gastric cancer
second-line treatment
chemotherapy
Apatinib mesylate
immunotherapy
PD-1 antibody
Lead sponsor: Tianjin Medical University Cancer Institute and Hospital
Sponsor class: OTHER
First posted: 2021-08-27
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 .

Eligibility criteria: 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.

Primary outcomes:
measure: The Overall Response Rate
timeFrame: From 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
measure: Progression Free Survival
timeFrame: From 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
Secondary outcomes:
measure: Overall survival
timeFrame: From date of randomization until the date of death from any cause or the last visit date, whichever came first, assessed up to 60 months
measure: Disease Control rate
timeFrame: From 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
measure: adverse events
timeFrame: Until 3 months after the end of the treatment
Other outcomes:
measure: biomolecular markers
timeFrame: From the begaining of treatment, then every 2 months after treatment, until the last time after treatment， assessed up to 24 months
Locations:
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
Study officials:
affiliation: Tianjin Medical University Cancer Institute and Hospital
name: Ting Deng, MD
role: PRINCIPAL_INVESTIGATOR
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