Apatinib Plus XELOX as Neoadjuvant Therapy in Locally Advanced Gastric Cancer

Gastric Cancer Clinical Trial

Official title:

Apatinib Plus XELOX Regime as Neoadjuvant Therapy in Locally Advanced Gastric Cancer Patients With Lymph Node Metastasis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03229096
• Other study ID #: ZSGC-002
• Status: Recruiting
• Phase: Phase 2
• Start date: February 1, 2017
• Est. completion date: December 1, 2021

Study information

• Verified date: June 2019
• Source: Shanghai Zhongshan Hospital
• Contact: Zhaoqing Tang, MD
• Phone: 86-21-64041990
• Email: tang.zhaoqing[@]zs-hospital.sh.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Apatinib plus XELOX regime as Neoadjuvant Therapy in Locally Advanced Gastric Cancer PatientsWith lymph node metastasis

Description:

This is a Single-center, Open-label, Single-arm,Non-randomized exploratory clinical trial evaluating the efficacy and safety of Apatinib plus XELOX regime as Neoadjuvant Therapy in Locally Advanced Gastric Cancer Patients With lymph node metastasis

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 35
• Est. completion date: December 1, 2021
• Est. primary completion date: November 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Adult patients, age =18 years.

2. Karnofsky score 70%.

3. Histologically confirmed adenocarcinoma of gastric cancer with Lauren classification Clinically diagnosed stage T2-T4aN+M0 according to CT/MRI scan.

4. At least one measurable and evaluable disease based on response evaluation criteria in solid tumors (RECIST v1.1), that is one or more perigastric lymph note were greater than or equal to 1.5cm in diameter.

5. Laparoscopic exploration confirms no peritoneal metastasis and negative peritoneal lavage.

6. Physical condition and adequate organ function to ensure the success of abdominal surgery.

7. Adequate hematological function: Neutrophil count = 1.5 × 109/L, Platelets = 100 × 109/L and Hemoglobin =8g/dL. Adequate liver function: Total bilirubin = 1.5 × upper limit of normal (ULN); AST (SGOT) and ALT (SGPT) < 2.5 × ULN. ALP = 2.5 × upper limit of normal (ULN); ALB =30g/L.Adequate renal function: Serum creatinine = 1 x ULN, and serum albumin=30g/L.

8. Life expectancy of more than 5 years without serious concomitant diseases.

9. Written (signed) informed consent.

10. Able to comply with study and follow-up procedures.

11. Consent to provide tissue sample.

Exclusion Criteria:

1. Pregnant or lactating women.

2. pregnancy tests before entering the group (in serum) of the childbearing age women were positive, or no pregnancy tests.

3. patients with distant metastases or local unresectable factors.

4. tumor stage considered as cT1 by imaging or ultrasound gastroscopy.

5. Patients who received prior anti-tumor therapy including cytotoxic chemotherapy, radiotherapy, hormonal therapy and immunotherapy.

6. History of other malignancies within the last 5 years except cured basal cell carcinoma of skin and carcinoma in situ of uterine cervix.

7. History of significant neurological or mental disorder, including seizures or dementia, which may interfere compliance and sign of consent inform.

8. Unstable, persistent cardiac disease despite medicinal treatment; myocardial infarction within 12 months before the start of the trial.

9. Patients with poor-controlled arterial hypertension (systolic pressure = 140 mmHg and/or diastolic pressure = 90 mm Hg) despite standard medical management.

10. Ileus, chronic inflammatory intestinal disease or extensive resection of the small intestine and other disorders which limit drug absorption.

11. Patients who experienced GI bleeding within two weeks, or with high risk of bleeding.

12. Patients with symptomatic peripheral neuropathy NCI CTC version> 1.0 grade, except only the deficiency of Deep tendon reflex.

13. Organ transplant patient need immunosuppression treatment.

14. Active or uncontrolled severe infection or other severe and /or uncontrolled diseases

15. Patients with moderate or severe chronic kidney disease estimated glomerular filtration rate=50 ml/min or serum creatinine =the upper limit of normal(ULN),

16. deficiency of dihydropyrimidine dehydrogenase (DPD)

17. Allergy to the drugs in this protocol

18. Less than 4 weeks from the last clinical trial.

Related Conditions & MeSH terms

• Chemotherapeutic Toxicity
• Chemotherapy Effect
• Gastric Cancer
• Stomach Neoplasms

Intervention

Drug:
• Apatinib plus XELOX
three weeks is one cycle, 4 cycles followed by radical gastrectomy. Apatinib: 250 mg, p.o., qd, every 3 weeks for the first two cycles. if no level 3 or severer AEs happened, change apatinib to 500mg, p.o.,qd, otherwise keep 250mg in the third cycle. no apatinib in the fourth cycle. Capecitabine: 1000mg/m2, p.o., bid, D1-14, every 3 weeks (treatment for 2 weeks and rest 1 week). Oxaliplatin: 130mg/m2, i.v. over 2h, D1, every 3 weeks.

Locations

Country	Name	City	State
China	ZhongShan hospital FuDan university	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Zhongshan Hospital

Country where clinical trial is conducted

China, 

References & Publications (17)

Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. doi: 10.1016/S0140-6736(10)61121-X. Epub 2010 Aug 19. Erratum in: Lancet. 2010 Oct 16;376(9749):1302. — View Citation

Boku N, Yamamoto S, Fukuda H, Shirao K, Doi T, Sawaki A, Koizumi W, Saito H, Yamaguchi K, Takiuchi H, Nasu J, Ohtsu A; Gastrointestinal Oncology Study Group of the Japan Clinical Oncology Group. Fluorouracil versus combination of irinotecan plus cisplatin versus S-1 in metastatic gastric cancer: a randomised phase 3 study. Lancet Oncol. 2009 Nov;10(11):1063-9. doi: 10.1016/S1470-2045(09)70259-1. Epub 2009 Oct 7. — View Citation

Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ, MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006 Jul 6;355(1):11-20. — View Citation

Fujitani K, Yang HK, Mizusawa J, Kim YW, Terashima M, Han SU, Iwasaki Y, Hyung WJ, Takagane A, Park DJ, Yoshikawa T, Hahn S, Nakamura K, Park CH, Kurokawa Y, Bang YJ, Park BJ, Sasako M, Tsujinaka T; REGATTA study investigators. Gastrectomy plus chemotherapy versus chemotherapy alone for advanced gastric cancer with a single non-curable factor (REGATTA): a phase 3, randomised controlled trial. Lancet Oncol. 2016 Mar;17(3):309-18. doi: 10.1016/S1470-2045(15)00553-7. Epub 2016 Jan 26. — View Citation

Inoue K, Nakane Y, Kogire M, Fujitani K, Kimura Y, Imamura H, Tamura S, Okano S, Kwon AH, Kurokawa Y, Shimokawa T, Takiuchi H, Tsujinaka T, Furukawa H. Phase II trial of preoperative S-1 plus cisplatin followed by surgery for initially unresectable locally advanced gastric cancer. Eur J Surg Oncol. 2012 Feb;38(2):143-9. doi: 10.1016/j.ejso.2011.11.009. Epub 2011 Dec 9. — View Citation

Ito S, Sano T, Mizusawa J, Takahari D, Katayama H, Katai H, Kawashima Y, Kinoshita T, Terashima M, Nashimoto A, Nakamori M, Onaya H, Sasako M. A phase II study of preoperative chemotherapy with docetaxel, cisplatin, and S-1 followed by gastrectomy with D2 plus para-aortic lymph node dissection for gastric cancer with extensive lymph node metastasis: JCOG1002. Gastric Cancer. 2017 Mar;20(2):322-331. doi: 10.1007/s10120-016-0619-z. Epub 2016 Jun 14. — View Citation

Iwasaki Y, Sasako M, Yamamoto S, Nakamura K, Sano T, Katai H, Tsujinaka T, Nashimoto A, Fukushima N, Tsuburaya A; Gastric Cancer Surgical Study Group of Japan Clinical Oncology Group. Phase II study of preoperative chemotherapy with S-1 and cisplatin followed by gastrectomy for clinically resectable type 4 and large type 3 gastric cancers (JCOG0210). J Surg Oncol. 2013 Jun;107(7):741-5. doi: 10.1002/jso.23301. Epub 2013 Feb 11. — View Citation

Kataoka K, Tokunaga M, Mizusawa J, Machida N, Katayama H, Shitara K, Tomita T, Nakamura K, Boku N, Sano T, Terashima M, Sasako M; Stomach Cancer Study Group/Japan Clinical Oncology Group. A randomized Phase II trial of systemic chemotherapy with and without trastuzumab followed by surgery in HER2-positive advanced gastric or esophagogastric junction adenocarcinoma with extensive lymph node metastasis: Japan Clinical Oncology Group study JCOG1301 (Trigger Study). Jpn J Clin Oncol. 2015 Nov;45(11):1082-6. doi: 10.1093/jjco/hyv134. Epub 2015 Sep 9. — View Citation

Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, Miyashita K, Nishizaki T, Kobayashi O, Takiyama W, Toh Y, Nagaie T, Takagi S, Yamamura Y, Yanaoka K, Orita H, Takeuchi M. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol. 2008 Mar;9(3):215-21. doi: 10.1016/S1470-2045(08)70035-4. Epub 2008 Feb 20. — View Citation

Li J, Qin S, Xu J, Xiong J, Wu C, Bai Y, Liu W, Tong J, Liu Y, Xu R, Wang Z, Wang Q, Ouyang X, Yang Y, Ba Y, Liang J, Lin X, Luo D, Zheng R, Wang X, Sun G, Wang L, Zheng L, Guo H, Wu J, Xu N, Yang J, Zhang H, Cheng Y, Wang N, Chen L, Fan Z, Sun P, Yu H. Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Apatinib in Patients With Chemotherapy-Refractory Advanced or Metastatic Adenocarcinoma of the Stomach or Gastroesophageal Junction. J Clin Oncol. 2016 May 1;34(13):1448-54. doi: 10.1200/JCO.2015.63.5995. Epub 2016 Feb 16. — View Citation

Okines AF, Langley RE, Thompson LC, Stenning SP, Stevenson L, Falk S, Seymour M, Coxon F, Middleton GW, Smith D, Evans L, Slater S, Waters J, Ford D, Hall M, Iveson TJ, Petty RD, Plummer C, Allum WH, Blazeby JM, Griffin M, Cunningham D. Bevacizumab with peri-operative epirubicin, cisplatin and capecitabine (ECX) in localised gastro-oesophageal adenocarcinoma: a safety report. Ann Oncol. 2013 Mar;24(3):702-9. doi: 10.1093/annonc/mds533. Epub 2012 Oct 28. — View Citation

Sano T, Coit DG, Kim HH, Roviello F, Kassab P, Wittekind C, Yamamoto Y, Ohashi Y. Proposal of a new stage grouping of gastric cancer for TNM classification: International Gastric Cancer Association staging project. Gastric Cancer. 2017 Mar;20(2):217-225. doi: 10.1007/s10120-016-0601-9. Epub 2016 Feb 20. — View Citation

Sasako M, Sano T, Yamamoto S, Kurokawa Y, Nashimoto A, Kurita A, Hiratsuka M, Tsujinaka T, Kinoshita T, Arai K, Yamamura Y, Okajima K; Japan Clinical Oncology Group. D2 lymphadenectomy alone or with para-aortic nodal dissection for gastric cancer. N Engl J Med. 2008 Jul 31;359(5):453-62. doi: 10.1056/NEJMoa0707035. — View Citation

Songun I, Putter H, Kranenbarg EM, Sasako M, van de Velde CJ. Surgical treatment of gastric cancer: 15-year follow-up results of the randomised nationwide Dutch D1D2 trial. Lancet Oncol. 2010 May;11(5):439-49. doi: 10.1016/S1470-2045(10)70070-X. Epub 2010 Apr 19. — View Citation

Tsuburaya A, Mizusawa J, Tanaka Y, Fukushima N, Nashimoto A, Sasako M; Stomach Cancer Study Group of the Japan Clinical Oncology Group. Neoadjuvant chemotherapy with S-1 and cisplatin followed by D2 gastrectomy with para-aortic lymph node dissection for gastric cancer with extensive lymph node metastasis. Br J Surg. 2014 May;101(6):653-60. doi: 10.1002/bjs.9484. Epub 2014 Mar 25. — View Citation

Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov O, Kim TY, Cunningham D, Rougier P, Komatsu Y, Ajani J, Emig M, Carlesi R, Ferry D, Chandrawansa K, Schwartz JD, Ohtsu A; RAINBOW Study Group. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1224-35. doi: 10.1016/S1470-2045(14)70420-6. Epub 2014 Sep 17. — View Citation

Yoshikawa T, Sasako M, Yamamoto S, Sano T, Imamura H, Fujitani K, Oshita H, Ito S, Kawashima Y, Fukushima N. Phase II study of neoadjuvant chemotherapy and extended surgery for locally advanced gastric cancer. Br J Surg. 2009 Sep;96(9):1015-22. doi: 10.1002/bjs.6665. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate (ORR)	Both CR and PR according to Response Evaluation Criteria in Solid Tumors RECIST Version 1.1	3 months
Secondary	Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	The safety of the the perioperative treatment, percentage of grade 3 or 4 adverse events as safety profile of perioperative treatments	30 days
Secondary	Pathological response rate (pRR)	Briefly, pathCR (Pathological complete rate) was defined as an absence of carcinoma cells in the primary site, and pathologic partial response (pathPR) was defined as less than 10% residual carcinoma cells in the specimen.	30 days
Secondary	3-year disease free survival rate		3 years
Secondary	3-year overall survival rate		3 years