Efficacy and Safety of Apatinib Combined With S-1 for Patients With Advance Gastric Cancer

NCT04338438 | Completed Phase 2

• 1 other identifier: BFH-Apatinib&S-1
• Study Type: interventional
• Target: 37
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a single-arm, interventional study aimed to observe the efficacy and safety of Apatinib combined with S-1 for patients with advanced gastric cancer refractory to oxaliplatin plus capecitabine combination therapy

Conditions

Gastric Cancer

Keywords

late-stage

Outcome Measures

Primary Outcomes (2)

• median progression-free survival(mPFS)

  The median duration of time between when a patient with oncological disease receives treatment and when the disease progresses or death due to any cause occurs.

  2 years

• median overall survival(mOS）

  The median time from treatment to the last follow-up or death.

  2 years

Secondary Outcomes (2)

• objective response rate(ORR)

  2 years

• disease control rate(DCR) DCR

  2 years

Study Arms (1)

Apatinib Mesylate tablets combined with S-1 capsules

EXPERIMENTAL

single arm trial: apatinib 500 mg once daily, across entire cycle and S-1 60 mg twice daily, on the first 14 days of a 21-day cycle. Medication was continued until the disease progression, withdrawal requirement, or intolerable adverse events

Drug: Apatinib Mesylate tablets combined with S-1 capsules

Interventions

Apatinib Mesylate tablets combined with S-1 capsules DRUG

Apatinib Mesylate tablets combined with S-1 capsules, p.o.

Apatinib Mesylate tablets combined with S-1 capsules

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient has provided signed informed consent and is amenable to compliance with protocol schedules and testing.
• The patient is at least 18 years of age (or of an acceptable age according to local regulations, whichever is older).
• The patient has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 -2 at study entry.
• The patient has a histopathologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction (GEJ) adenocarcinoma.
• The patient has metastatic disease or locally advanced, unresectable or recurrent disease.
• The patient has experienced documented objective radiographic or clinical disease progression (eg, any new or worsening malignant effusion documented by ultrasound examination) which may be confirmed by pathologic criteria (histology and/or cytology) if appropriate, during first-line therapy, or within 6 months after the last dose of first-line therapy with Oxaliplatin plus Capecitabine doublet with or without anthracycline (epirubicin or doxorubicin) for unresectable or metastatic disease.
• The patient has resolution to Grade ≤1 by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03, of all clinically significant toxic effects of prior locoregional therapy, surgery, or other anticancer therapy.
• The patient has adequate organ function, defined as:
• Total bilirubin ≤1.5 times upper limit of normal value (ULN), aspartate transaminase (AST) and alanine transaminase (ALT) ≤3 ULN for ALT/AST if no liver metastases, \<5 ULN if liver metastases;
• Serum creatinine ≤1.5 ULN or calculated creatinine clearance (per the Cockcroft-Gault formula or equivalent and/or 24-hour urine collection) ≥50 mL/min;
• Absolute neutrophil count (ANC) ≥1.5 109 /L, hemoglobin ≥ 9 g/dL (5.58 mmol/L; packed red blood cell transfusions are not allowed within one week prior to baseline hematology profile), and platelets ≥100 109 /L;
• International Normalized Ratio (INR) ≤ 1.5 or Prothrombin time (PT) ≤1.5 ULN;
• Partial thromboplastin time (PTT/APTT) ≤ 1.5 ULN.
• The patient's urinary protein is ≤1+ on dipstick or routine urinalysis. If urine dipstick or routine analysis indicates proteinuria ≥2+, then a 24-hour urine must be collected and must demonstrate \<1000 mg of protein in 24 hours to allow participation in the study.
• The patient, if female, is surgically sterile, postmenopausal, or compliant with a highly effective contraceptive method (failure rate \<1%) during and for 12 weeks after the treatment period (oral hormonal contraception alone is not considered highly effective and must be used in combination with a barrier method). If male, the patient is surgically sterile or compliant with a highly effective contraceptive regimen during and for 6 months after the treatment period. The label requirements with regard to the methods and duration of contraception during and after treatment with paclitaxel can differ between countries. Country specific requirements will apply only if they are more stringent than those already stipulated in the protocol.

You may not qualify if:

• The patient has squamous cell or undifferentiated gastric cancer.
• The patient has undergone major surgery within 28 days prior to medications, or central venous access device placement within 7 days prior to medications.
• The patient has received any chemotherapy other than Oxaliplatin plus Capecitabine for advanced gastric or GEJ adenocarcinoma.
• The patient has received previous systemic chemotherapy with a cumulative dose of \>900 mg/m2 of epirubicin or \>400 mg/m2 of doxorubicin.
• The patient has received any previous systemic therapy (including investigational agents) targeting vascular endothelial growth factor(VEGF) or the vascular endothelial growth factor receptor(VEGFR) signaling pathways. Other previous targeted therapies are permitted, if stopped at least 28 days prior to randomization.
• The patient has a history of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered "significant") during the 3 months prior to randomization.
• The patient is receiving chronic therapy with nonsteroidal anti-inflammatory agents (NSAIDs, eg, indomethacin, ibuprofen, naproxen or similar agents) or other anti-platelet agents (eg, clopidogrel, ticlopidine, dipyridamole, anagrelide). Aspirin use at doses up to 325 mg/day is permitted.
• The patient has significant bleeding disorders, vasculitis, or had a significant bleeding episode from the gastrointestinal tract within 3 months prior to study entry.
• History of gastrointestinal perforation and/or fistulae within 6 months prior to medications.
• The patient has symptomatic congestive heart failure (New York Heart Association II-IV) or symptomatic or poorly controlled cardiac arrhythmia.
• The patient has experienced any arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to randomization.
• The patient has uncontrolled arterial hypertension ≥150/≥90 mm Hg despite standard medical management.
• The patient has a serious or non healing wound or peptic ulcer or bone fracture within 28 days prior to medications.
• The patient has a bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection (hemicolectomy or extensive small intestine resection with chronic diarrhea), Crohn's disease, ulcerative colitis, or chronic diarrhea.
• The patient has a serious illness or medical condition(s) including, but not limited to the following:

Sponsors & Collaborators

• Beijing Friendship Hospital: lead

Related Publications (9)

• Noh SH, Park SR, Yang HK, Chung HC, Chung IJ, Kim SW, Kim HH, Choi JH, Kim HK, Yu W, Lee JI, Shin DB, Ji J, Chen JS, Lim Y, Ha S, Bang YJ; CLASSIC trial investigators. Adjuvant capecitabine plus oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): 5-year follow-up of an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Nov;15(12):1389-96. doi: 10.1016/S1470-2045(14)70473-5. Epub 2014 Oct 15.

  PMID: 25439693 BACKGROUND

• Sakuramoto S, Sasako M, Yamaguchi T, Kinoshita T, Fujii M, Nashimoto A, Furukawa H, Nakajima T, Ohashi Y, Imamura H, Higashino M, Yamamura Y, Kurita A, Arai K; ACTS-GC Group. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007 Nov 1;357(18):1810-20. doi: 10.1056/NEJMoa072252.

  PMID: 17978289 BACKGROUND

• Lan CY, Wang Y, Xiong Y, Li JD, Shen JX, Li YF, Zheng M, Zhang YN, Feng YL, Liu Q, Huang HQ, Huang X. Apatinib combined with oral etoposide in patients with platinum-resistant or platinum-refractory ovarian cancer (AEROC): a phase 2, single-arm, prospective study. Lancet Oncol. 2018 Sep;19(9):1239-1246. doi: 10.1016/S1470-2045(18)30349-8. Epub 2018 Aug 3.

  PMID: 30082170 BACKGROUND

• Li J, Qin S, Xu J, Guo W, Xiong J, Bai Y, Sun G, Yang Y, Wang L, Xu N, Cheng Y, Wang Z, Zheng L, Tao M, Zhu X, Ji D, Liu X, Yu H. Apatinib for chemotherapy-refractory advanced metastatic gastric cancer: results from a randomized, placebo-controlled, parallel-arm, phase II trial. J Clin Oncol. 2013 Sep 10;31(26):3219-25. doi: 10.1200/JCO.2013.48.8585. Epub 2013 Aug 5.

  PMID: 23918952 BACKGROUND

• Roviello G, Ravelli A, Polom K, Petrioli R, Marano L, Marrelli D, Roviello F, Generali D. Apatinib: A novel receptor tyrosine kinase inhibitor for the treatment of gastric cancer. Cancer Lett. 2016 Mar 28;372(2):187-91. doi: 10.1016/j.canlet.2016.01.014. Epub 2016 Jan 18.

  PMID: 26797419 BACKGROUND

• Liang W, Guan W, Chen R, Wang W, Li J, Xu K, Li C, Ai Q, Lu W, Liang H, Li S, He J. Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China. Lancet Oncol. 2020 Mar;21(3):335-337. doi: 10.1016/S1470-2045(20)30096-6. Epub 2020 Feb 14. No abstract available.

  PMID: 32066541 BACKGROUND

• Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020 Jan;70(1):7-30. doi: 10.3322/caac.21590. Epub 2020 Jan 8.

  PMID: 31912902 BACKGROUND

• Zong L, Abe M, Seto Y, Ji J. The challenge of screening for early gastric cancer in China. Lancet. 2016 Nov 26;388(10060):2606. doi: 10.1016/S0140-6736(16)32226-7. No abstract available.

  PMID: 27894662 BACKGROUND

• Jing C, Bai Z, Zhang J, Jiang H, Yang X, Yan S, Yin J, Cai J, Zhang Z, Deng W. Apatinib plus S-1 for previously treated, advanced gastric or gastro-oesophageal junction adenocarcinoma: a phase 2, single-arm, prospective study. J Gastrointest Oncol. 2021 Oct;12(5):2035-2044. doi: 10.21037/jgo-21-186.

  PMID: 34790371 DERIVED

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

apatinib; S 1 (combination)

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Study Officials

• Wei Deng, M.D.

  Beijing Friendship Hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 5, 2020
• First Posted: April 8, 2020
• Study Start: May 1, 2015
• Primary Completion: April 30, 2019
• Study Completion: January 31, 2020
• Last Updated: November 10, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: 2020.12\~
• Access Criteria: via reasonable email requests