Maintenance Treatment With S-1 in Gastric Cancer Patients

Cancer of Stomach Clinical Trial

Official title:

Maintenance Treatment With S-1 Versus Observation After First-line Chemotherapy in Patients With Advanced Gastric Cancer: a Randomized Phase II Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03701373
• Other study ID #: S-1 maintenance study
• Status: Recruiting
• Phase: Phase 2
• Start date: January 1, 2016
• Est. completion date: December 2018

Study information

• Verified date: October 2018
• Source: Sun Yat-sen University
• Contact: Rui-hua Xu, PHD
• Phone: +86-20-87343295
• Email: xurh[@]sysucc.org.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Gastric cancer remains the third leading cause of cancer-related death worldwide and is especially frequent in East Asia. Fluoropyrimidines are the backbone of first-line chemotherapy for advanced gastric cancer (AGC), and S-1 provides new option with its simplicity and convenience.

5-Fluorouracil (5-FU) was the only efficacious treatment for AGC before the nineties of the 20th century, and afterwards with the discovery of chemotherapy such as cisplatin, oxaliplatin, S-1 and capecitabine, response rate as well as survival had been improved greatly.

Most of AGC will progress after first-line treatment; therefore, seeking an efficient and low toxic maintaining regimen to prolong progression-free survival (PFS) becomes a hot topic in oncologic field. Some clinical researches demonstrated maintenance treatment for advanced colorectal cancer (CRC) and lung cancer. The investigators had conducted a phase III clinical trial that demonstrated capecitabine maintenance versus observation prolonged PFS significantly after first-line chemotherapy with FOLFOX or XELOX regimens in advanced CRC. In AGC, several retrospective studies revealed patients receiving 5-FU/leucovorin(LV), capecitabine, or trastuzumab maintaining therapy experienced significantly longer PFS than that stopped chemotherapy after first-line chemotherapy. Some one-arm phase II clinical trials found 5-FU/LV, capecitabine, S-1, capecitabine plus bevacirumab, or capecitabine plus bevacirumab plus trastuzumab maintenance seemed to yield sound PFS and good tolerance. However, there were no randomized controlled clinical trials for maintenance treatment of these regimens in AGC, except that a phase II Chinese randomized controlled trial of Uracil and Tegafur (UFT) versus observation experienced early termination.

Above all, so far, there is no data to demonstrate that regular 2-6 months of chemotherapy followed by maintenance treatment could prolong PFS and OS for AGC. S-1 is effective for gastric cancer, and was approved as palliative treatment for advanced gastric cancer and adjuvant treatment; in addition, with its relative less frequency of side effects and convenient oral administration, S-1 as maintenance regimen could be prone to be accepted by patients. Therefore, the current study is designed to investigate that S-1 as maintenance treatment after first-line palliative chemotherapy could improve PFS and OS for patients with advanced gastric cancer through a perspective randomized clinical study.

Description:

Patients with AGC who achieved objective response or stable disease after 2-6 months of first-line chemotherapy were randomly assigned to one of two groups, to receive either S-1 (40 mg for BSA<1.25 m2, 50 mg for 1.25≤BSA<1.50 m2 and 60 mg for BSA≥1.50 m2 b.i.d. on days 1-14, q3w) as maintenance therapy or observation. The treatment will continue until disease progression or unacceptable toxicity.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 2018
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Age older than 18 years

• Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1

• At least one measurable lesion according to the Response Evaluation Criteria in Solid Tumor (RECIST version 1.0)

• Histologically confirmed gastric cancer with inoperable locally advanced or recurrent and/or metastatic disease, not amenable to curative therapy

• No previous chemotherapy for metastatic GC was allowed, the interval after the end of adjuvant/neoadjuvant chemotherapy beyond 6 months was allowable

• Life expectancy of at least 3 months

• Adequate hematologic, hepatic and renal function. Neutrophil count = 1.5 × 109/L; platelet count = 100 × 109/L; Serum bilirubin = 1.5 × upper limit of normal (ULN), AST or ALT = 2.5 × ULN (or = 5 × ULN in patients with liver metastases), alkaline phosphatase = 2.5 × ULN (or = 5 × ULN in patients with liver metastases, or = 10 × ULN in patients with bone but no liver metastases); serum creatinine = 1.5 × ULN;and albumin = 25 g/L

• Patients who achieved objective response or stable disease after 2-6 month first-line chemotherapy

• The first-line chemotherapy regimens were doublets including platinum (cisplatin or oxaliplatin) plus fluoropyrimidine (5-FU, capecitabine, or S-1)

• Signed informed consent

Exclusion Criteria:

• Known hypersensitivity to platinum (cisplatin or oxaliplatin) or fluoropyrimidine (5-FU, capecitabine, or S-1)

• History or clinical evidence of brain metastases

• Previous chemotherapy for metastatic disease

• Positive serum pregnancy test in women of childbearing potential

• Subjects with reproductive potential not willing to use an effective method of contraception

• Received any investigational drug treatment within 4 weeks of start of study treatment

• Other prior malignancies in the past 5 years

• Unresolved bowel obstruction or malabsorption syndrome

Related Conditions & MeSH terms

• Cancer of Stomach
• Gastric Cancer Stage IV
• Stomach Neoplasms

Intervention

Drug:
• S-1 maintenance
S-1 maintenance till disease progression or untolerable toxicities, in oral doses of 40 mg (BSA<1.25 m2), 50 mg (1.25=BSA<1.50 m2) and 60 mg (BSA=1.50 m2) b.i.d. on days 1-14 for each 21-day cycle.

Other:
• Observation
Observation without anti-tumor treatment

Locations

Country	Name	City	State
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

References & Publications (9)

Chen J, Shen W, Xia J, Xu R, Zhu M, Xu M. [Effect of S-1 maintenance chemotherapy following DCF regimen in patients with advanced gastric cancer]. Nan Fang Yi Ke Da Xue Xue Bao. 2014 Jun;34(7):1057-60. Chinese. — View Citation

Eren OO, Ozturk MA, Sonmez OU, Oyan B. Safety, Feasibility, and Efficacy of Capecitabine Maintenance in Patients With Advanced Gastric Cancer: A Retrospective Study. Am J Ther. 2016 Nov/Dec;23(6):e1493-e1497. — View Citation

Li W, Zhao X, Wang H, Liu X, Zhao X, Huang M, Qiu L, Zhang W, Chen Z, Guo W, Li J, Zhu X. Maintenance treatment of Uracil and Tegafur (UFT) in responders following first-line fluorouracil-based chemotherapy in metastatic gastric cancer: a randomized phase II study. Oncotarget. 2017 Jun 6;8(23):37826-37834. doi: 10.18632/oncotarget.13922. — View Citation

Luo HY, Li YH, Wang W, Wang ZQ, Yuan X, Ma D, Wang FH, Zhang DS, Lin DR, Lin YC, Jia J, Hu XH, Peng JW, Xu RH. Single-agent capecitabine as maintenance therapy after induction of XELOX (or FOLFOX) in first-line treatment of metastatic colorectal cancer: randomized clinical trial of efficacy and safety. Ann Oncol. 2016 Jun;27(6):1074-81. doi: 10.1093/annonc/mdw101. Epub 2016 Mar 2. — View Citation

Meulendijks D, Beerepoot LV, Boot H, de Groot JW, Los M, Boers JE, Vanhoutvin SA, Polee MB, Beeker A, Portielje JE, de Jong RS, Goey SH, Kuiper M, Sikorska K, Beijnen JH, Tesselaar ME, Schellens JH, Cats A. Trastuzumab and bevacizumab combined with docetaxel, oxaliplatin and capecitabine as first-line treatment of advanced HER2-positive gastric cancer: a multicenter phase II study. Invest New Drugs. 2016 Feb;34(1):119-28. doi: 10.1007/s10637-015-0309-4. Epub 2015 Dec 8. — View Citation

Meulendijks D, de Groot JW, Los M, Boers JE, Beerepoot LV, Polee MB, Beeker A, Portielje JE, Goey SH, de Jong RS, Vanhoutvin SA, Kuiper M, Sikorska K, Pluim D, Beijnen JH, Schellens JH, Grootscholten C, Tesselaar ME, Cats A. Bevacizumab combined with docetaxel, oxaliplatin, and capecitabine, followed by maintenance with capecitabine and bevacizumab, as first-line treatment of patients with advanced HER2-negative gastric cancer: A multicenter phase 2 study. Cancer. 2016 May 1;122(9):1434-43. doi: 10.1002/cncr.29864. Epub 2016 Mar 11. — View Citation

Palacio S, Loaiza-Bonilla A, Kittaneh M, Kyriakopoulos C, Ochoa RE, Escobar M, Arango B, Restrepo MH, Merchan JR, Rocha Lima CM, Hosein PJ. Successful use of Trastuzumab with anthracycline-based chemotherapy followed by trastuzumab maintenance in patients with advanced HER2-positive gastric cancer. Anticancer Res. 2014 Jan;34(1):301-6. — View Citation

Petrioli R, Francini E, Roviello F, Marrelli D, Miano ST, Fiaschi AI, Laera L, Bellini MA, Roviello G. Treatment of advanced oesophagogastric cancer with FOLFOX-4 regimen followed by leucovorin/bolus and continuous infusion 5-FU as maintenance chemotherapy in patients aged = 75 years with impaired performance status. J Geriatr Oncol. 2015 Sep;6(5):380-6. doi: 10.1016/j.jgo.2015.06.002. Epub 2015 Jul 27. — View Citation

Qiu MZ, Wei XL, Zhang DS, Jin Y, Zhou YX, Wang DS, Ren C, Bai L, Luo HY, Wang ZQ, Wang FH, Li YH, Yang DJ, Xu RH. Efficacy and safety of capecitabine as maintenance treatment after first-line chemotherapy using oxaliplatin and capecitabine in advanced gastric adenocarcinoma patients: a prospective observation. Tumour Biol. 2014 May;35(5):4369-75. doi: 10.1007/s13277-013-1574-5. Epub 2014 Feb 11. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	maintenance progression-free survival (PFS)	The Kaplan-Meier survival from randomization to maintenance or observation until the date of first documented progression or date of death from any cause, whichever came first.	from date of randomization to maintenance or observation until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
Secondary	progression-free survival from induction treatment (PFS2)	The Kaplan-Meier survival from induction treatment (the initiation date of first-line chemotherapy) until the date of first documented progression or date of death from any cause after maintenance treatment or observation, whichever came first	from induction treatment (the initiation date of first-line chemotherapy) until the date of first documented progression or date of death from any cause after maintenance treatment or observation, whichever came first, assessed up to 2 years
Secondary	overall survival (OS)	The Kaplan-Meier survival from induction treatment (the initiation date of first-line chemotherapy) until death from any cause or the last follow-up date.	from induction treatment (the initiation date of first-line chemotherapy) until death from any cause or the last follow-up date, assessed up to 2 years.
Secondary	toxicity relevant to S-1 maintenance/observation	any toxicities occurring during the treatment of S-1 maintenance/observation	from date of randomization to maintenance or observation until the date of first documented progression or unaccepted toxicities, assessed up to 30 days after the last oral administration of S-1.