A Phase I Study of S-1 in Combination With Radiotherapy in Locally Advanced or Recurrent Gastric Cancer

NCT01291407 | Completed Phase 1 DMC

• 1 other identifier: CH-GI-012
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine maximum tolerated dose (MTD), dose limiting toxicities (DLT) and recommend a proper dose for our phase II study of S-1 when combined with radiation therapy for locally advanced or recurrent gastric cancer.

Conditions

Gastrointestinal Neoplasms; Gastric Cancer

Keywords

Combined Modality; Gastric Cancer; Radiation Therapy; S-1

Outcome Measures

Primary Outcomes (1)

• To define dose limited toxicities(DLT) of S-1, peroral BID, in treatment days concurrently with radiation therapy (RT) in locally advanced or recurrent gastric cancer.

  Dose limited toxicities defined as below: leucopenia ≥4 neutropenia ≥ 4, anemia ≥ 3, thrombocytopenia ≥ 3, alanine aminotransferase/aspartate aminotransferase (AST) ≥ 3, alkaline phosphatase (ALT) ≥ 3, total bilirubin ≥ 3,blood urea nitrogen (BUN)/Cr ≥ 2,non-granular cell decreased fever ≥ 2, nausea/vomiting ≥ 2, fatigue ≥ 3, weight loss ≥ 3, diarrhea ≥ 3, abdominal pain ≥ 3, dysphagia ≥ 3, hand-foot syndrome ≥ 2, neurotoxicity ≥ 2.

  up to 9 weeks

Secondary Outcomes (1)

• To define maximum tolerated dose(MTD) of S-1, peroral BID, in treatment days concurrently with radiation therapy

  up to 9 weeks

Study Arms (1)

S-1,peroral BID,capsule

EXPERIMENTAL

Drug: S-1

Interventions

S-1 DRUG

S-1,30mg/m2/d,peroral BID,in treatment days concurrently with radiation therapy in a standard manner.

Also known as: an oral fluorinated pyrimidine combination

S-1,peroral BID,capsule

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically proven locally advanced gastric adenocarcinoma in patients undergoing R0, R1, R2 resection, or with unresectable or locoregional recurrent disease
• Any prior chemotherapy is allowed in this protocol.
• No distant metastasis in liver,lung,,bone,central nervous system(CNS),no peritoneal transplantation
• No prior abdominal or pelvic radiotherapy.
• Karnofsky performance status(KPS)≥ 70,predictive life span no less than 6 months
• Patients must have normal organ and marrow function as defined below:
• Leukocytes greater than or equal to 3,000 G/L
• Platelets: greater than or equal to 100,000/mm3
• Hemoglobin:greater than or equal to 10g/L
• Total bilirubin: within normal institutional limits
• AST/ALT: less than or equal to 1.5 times the upper limit
• Creatinine within normal upper limits
• Informed consent
• Without any serious complications,such as hypertension,coronary artery disease,psychiatric history.

You may not qualify if:

• Patients with other cancer history except cervical carcinoma in situ and non-malignant melanoma skin cancer
• With any distant metastasis in liver,lung,,bone,CNS,or peritoneal transplantation
• History of allergic reactions attributed to similar chemical or biologic complex to S-1
• Uncontrolled illness including, but not limited to, active infection, symptomatic heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness
• History of myocardial infarction within the past 6 months or history of ventricular arrhythmia
• History of prior radiation to the abdomen
• Pregnant or lactating females

Sponsors & Collaborators

• Chinese Academy of Medical Sciences: lead

Study Sites (1)

Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)

Beijing, 100021, China

Location

Related Publications (13)

• Parkin DM, Pisani P, Ferlay J. Global cancer statistics. CA Cancer J Clin. 1999 Jan-Feb;49(1):33-64, 1. doi: 10.3322/canjclin.49.1.33.

  PMID: 10200776 BACKGROUND

• Taguchi T, Inuyama Y, Kanamaru R, Hasegawa K, Akazawa S, Niitani H, Furue H, Kurihara M, Ota K, Suga S, Ariyoshi Y, Takai S, Shimoyama T, Toge T, Takashima S, Sugimachi K, Hara Y, Fujita H, Kimura K, Saito T, Tsukagoshi S, Nakao I. [Phase I study of S-1. S-1 Study Group]. Gan To Kagaku Ryoho. 1997 Dec;24(15):2253-64. Japanese.

  PMID: 9422070 BACKGROUND

• van Groeningen CJ, Peters GJ, Schornagel JH, Gall H, Noordhuis P, de Vries MJ, Turner SL, Swart MS, Pinedo HM, Hanauske AR, Giaccone G. Phase I clinical and pharmacokinetic study of oral S-1 in patients with advanced solid tumors. J Clin Oncol. 2000 Jul;18(14):2772-9. doi: 10.1200/JCO.2000.18.14.2772.

  PMID: 10894878 BACKGROUND

• Cohen SJ, Leichman CG, Yeslow G, Beard M, Proefrock A, Roedig B, Damle B, Letrent SP, DeCillis AP, Meropol NJ. Phase I and pharmacokinetic study of once daily oral administration of S-1 in patients with advanced cancer. Clin Cancer Res. 2002 Jul;8(7):2116-22.

  PMID: 12114411 BACKGROUND

• Chu QS, Hammond LA, Schwartz G, Ochoa L, Rha SY, Denis L, Molpus K, Roedig B, Letrent SP, Damle B, DeCillis AP, Rowinsky EK. Phase I and pharmacokinetic study of the oral fluoropyrimidine S-1 on a once-daily-for-28-day schedule in patients with advanced malignancies. Clin Cancer Res. 2004 Aug 1;10(15):4913-21. doi: 10.1158/1078-0432.CCR-04-0469.

  PMID: 15297391 BACKGROUND

• Takahashi I, Kakeji Y, Emi Y, Sakurai M, Yonemura Y, Kimura Y, Maehara Y. S-1 in the treatment of advanced and recurrent gastric cancer: current state and future prospects. Gastric Cancer. 2003;6 Suppl 1:28-33. doi: 10.1007/s10120-003-0228-5.

  PMID: 12775017 BACKGROUND

• Sakata Y, Ohtsu A, Horikoshi N, Sugimachi K, Mitachi Y, Taguchi T. Late phase II study of novel oral fluoropyrimidine anticancer drug S-1 (1 M tegafur-0.4 M gimestat-1 M otastat potassium) in advanced gastric cancer patients. Eur J Cancer. 1998 Oct;34(11):1715-20. doi: 10.1016/s0959-8049(98)00211-1.

  PMID: 9893658 BACKGROUND

• Sugimachi K, Maehara Y, Horikoshi N, Shimada Y, Sakata Y, Mitachi Y, Taguchi T. An early phase II study of oral S-1, a newly developed 5-fluorouracil derivative for advanced and recurrent gastrointestinal cancers. The S-1 Gastrointestinal Cancer Study Group. Oncology. 1999 Oct;57(3):202-10. doi: 10.1159/000012032.

  PMID: 10545788 BACKGROUND

• Koizumi W, Kurihara M, Nakano S, Hasegawa K. Phase II study of S-1, a novel oral derivative of 5-fluorouracil, in advanced gastric cancer. For the S-1 Cooperative Gastric Cancer Study Group. Oncology. 2000 Apr;58(3):191-7. doi: 10.1159/000012099.

  PMID: 10765119 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

• Fujitani K, Tsujinaka T, Yamasaki H, Hirao M, Yoshida K, Kurokawa Y. Feasibility study of S-1 plus weekly docetaxel combined with concurrent radiotherapy in advanced gastric cancer refractory to first-line chemotherapy. Anticancer Res. 2009 Aug;29(8):3385-91.

  PMID: 19661361 BACKGROUND

• Saikawa Y, Kubota T, Kumagai K, Nakamura R, Kumai K, Shigematsu N, Kubo A, Kitajima M, Kitagawa Y. Phase II study of chemoradiotherapy with S-1 and low-dose cisplatin for inoperable advanced gastric cancer. Int J Radiat Oncol Biol Phys. 2008 May 1;71(1):173-9. doi: 10.1016/j.ijrobp.2007.09.010. Epub 2007 Nov 8.

  PMID: 17996385 BACKGROUND

• Li N, Xiang X, Zhao D, Wang X, Tang Y, Chi Y, Yang L, Jiang L, Jiang J, Shi J, Liu W, Fang H, Tang Y, Chen B, Lu N, Jing H, Qi S, Wang S, Liu Y, Song Y, Li Y, Zhang L, Jin J. Preoperative versus postoperative chemo-radiotherapy for locally advanced gastric cancer: a multicenter propensity score-matched analysis. BMC Cancer. 2022 Feb 26;22(1):212. doi: 10.1186/s12885-022-09297-7.

  PMID: 35219300 DERIVED

MeSH Terms

Conditions

Gastrointestinal Neoplasms; Stomach Neoplasms

Interventions

S 1 (combination)

Condition Hierarchy (Ancestors)

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

Study Officials

• Jing Jin, MD,PhD

  Department of Radiation Oncology,Cancer Hospital and Institute,CAMS

  PRINCIPAL INVESTIGATOR

• Yexiong Li, MD,PhD

  Department of Radiation Oncology,Cancer Hospital and Institute, CAMS

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr.

Study Record Dates

• First Submitted: February 7, 2011
• First Posted: February 8, 2011
• Study Start: November 1, 2010
• Primary Completion: August 1, 2013
• Study Completion: September 1, 2013
• Last Updated: September 18, 2013

Record last verified: 2013-09

Locations

CN (1)