Gastric Cancer
Conditions
Keywords
gastric cancer, second-line treatment, chemotherapy, Apatinib mesylate, immunotherapy, PD-1 antibody
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 .
Interventions
DRUGPD-1 antibody, paclitaxel or irinotecan, Apatinib mesylate
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.
Sponsors
Tianjin Medical University Cancer Institute and Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Overall Response Rate | 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 | The proportion of CR and PR |
| Progression Free Survival | 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 | Time from the start of treatment to the progression of the disease |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | 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 | Time from the start of treatment to the occurrence of death |
| Disease Control rate | 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 | The proportion of CR,PR and SD |
| adverse events | Until 3 months after the end of the treatment | The incidence of various adverse events |
Other
| Measure | Time frame | Description |
|---|---|---|
| biomolecular markers | From the begaining of treatment, then every 2 months after treatment, until the last time after treatment， assessed up to 24 months | Serum will be collected before medication and during each evaluation. Mass spectrometry or RNA sequencing technology will be used to detect the differences in the exosomal proteome and non-coding RNA group in the serum before medication. Screen out the group of exosomal protein/non-coding RNA components with obvious differences in the two groups of patients; and consider its biological function/signal pathway, and finally select 1-2 kinds of protein/non-coding RNA. |
Countries
China
Outcome results
None listed