Apatinib Combined With Chemotherapy Versus Chemotherapy in Second-line Gastric Cancer Receiving Prior Anti-PD-1 Therapy

Study Overview
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Brief Summary
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The study is a multicenter, open-label, randomized controlled clinical study. The purpose of the study is to evaluate the efficacy and safety of apatinib combined with chemotherapy versus chemotherapy in second-line gastric cancer receiving prior anti-PD-1 therapy.

Detailed Description
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60 patients who meet the inclusion criteria will receive apatinib combine with chemotherapy or chemotherapy until the disease progresses or intolerable. Apatinib: initial dose: 500mg,oral,once a day, after meal (try to take the medicine at the same time each day)

Official Title
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A Prospective, Multicenter, Randomized Controlled Study of Apatinib Combined With Chemotherapy Versus Chemotherapy in Second-line Gastric Cancer Receiving Prior Anti-PD-1 Therapy

Conditions
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Gastric Cancer, Randomized Controlled Study

Intervention / Treatment
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* Drug: Apatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: ≥18 years old, Female or Male; Pathologically diagnosed gastric or gastroesophageal junction adenocarcinoma (GEJ). Failure or intolerance of first-line chemotherapy which requires that the first-line chemotherapy regimen include the scheme based on anti-PD-1 drugs for no less than 2 months (Definition of treatment failure: intolerence of toxic side effects; disease progression during treatment; Or recurrence after the end of treatment.) Note: (1)The treatment of each line advanced disease includes one or more drugs with a medication time ≥ 1 cycle. (2) Early adjuvant/neo-adjuvant therapy is allowed. If recurrence occurs during adjuvant/neoadjuvant therapy or within ≤24 weeks after completion, adjuvant/neoadjuvant therapy is considered to be a first-line pre-systemic chemotherapy for advanced disease. (3) Early-stage immunotherapy, combined chemotherapy or combined targeted drugs are allowed (except for VEGFR inhibitors). Patients must have at least 1 lesion that is measurable using RECIST v1.1 criteria ECOG performance status 0-1. An expected survival of > 12 weeks. Has adequate sufficient organ and bone marrow functions. Patients whose adverse events caused by previous treatment have recovered to <= CTCAE 1 degree; And the interval between receiving nitroso or mitomycin ≥6 weeks; Receiving other cytotoxic drugs, radiotherapy or surgery ≥ 4 weeks, and the wound has healed completely. Fertile female subjects must undergo a serum-negative pregnancy test within 72 hours before starting the study drug Patients have agreed and signed the informed consent. Willingness and able to follow the planned visit, research treatment, laboratory examination and other test procedures. Exclusion Criteria: It is known that it's allergic to any test drug and its excipients. Previously received anti-angiogenic therapy, such as Ramucirumab and apatinib. patients with uncontrolled large amount of exudate [chest, pericardium, abdominal cavity] Patients with partial or complete gastrointestinal obstruction. Hypertension, which cannot be well controlled by antihypertensive drugs (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg). Patients with uncontrolled clinical symptoms or diseases of the heart. In the first 3 months of the study, patients who had significant clinical bleeding symptoms or had definite bleeding tendency; History of gastrointestinal perforation and/or fistulae within 6 months prior to medications. Long term use of aspirin, clopidogrel and other antiplatelet drugs, or warfarin and other anticoagulants; Received other therapy within 4 weeks. The patients who received systemic treatment with Chinese herbal medicine or immunomodulatory drugs According to the research's judgement, there are patients who seriously endanger the safety of patients or affect the patients who complete.(such as uncontrolled hypertension、diabetes、thyroid disease, etc) The patient has a serious or non healing wound or peptic ulcer or bone fracture; A patient with other malignancies within 3 years. patients whose adverse events (except hair loss) caused by previous treatment have not recovered to <= CTCAE 1 degree; The researchers considered unsuitable for inclusion.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Group<br>apatinib combine with chemotherapy. Apatinib: initial dose: 500mg,oral,once a day, after meal ( try to take the medicine at the same time each day) Recommended chemotherapy: docetaxel(60/75 mg/m2, d1, q3w)、albuminbound paclitaxel(125mg/m2, d1, d8, q3w) or (260mg/m2, d1, q3w)。 | Drug: Apatinib<br>* In experimental group, the drug used with apatinib and chemotherapy.<br>|
| No Intervention: Control Gtoup<br>chemotherapy Recommended chemotherapy: docetaxel(60/75 mg/m2, d1, q3w)、albuminbound paclitaxel(125mg/m2, d1, d8, q3w) or (260mg/m2, d1, q3w)。 | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival [PFS] | 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 | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective tumor response rate [ORR] | ORR is defined as the percentage of subjects having achieved confirmed Complete Response + Partial Response as best overall response according to radiological assessments. | 1year | 
| disease control rate [DCR] | Investigators will assess treatment response according to Response Evaluation Criteria in Solid Tumors 1.1（RECIST1.1） | 1year | 
| Duration of response [DoR] | Duration of response | 1year | 
| overall survival [OS] | OS is defined as the length of time from random assignment to death or to last contact. | 3year | 
| Adverse Events [AEs] | AEs are evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events v5.0 | 1year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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apatinib, chemotherapy, prior anti-PD-1 therapy