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

Gastric Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01291407
• Other study ID #: CH-GI-012
• Status: Completed
• Phase: Phase 1
• First received: February 7, 2011
• Last updated: September 17, 2013
• Start date: November 2010
• Est. completion date: September 2013

Study information

• Verified date: September 2013
• Source: Chinese Academy of Medical Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

This is a Phase I trial of S-1 given in treatment days with an oral dose from 30mg/m2/d to 80mg/m2/d, concurrently with radiation in patients with locally advanced or locally recurrent gastric cancer. Patients will be treated with external beam radiation therapy in a standard manner. S-1 will be administered for 6 dose levels,30/40/50/60/70/80mg/m2/d. Patients will be assessed for acute toxicities according to Common Toxicity Criteria for Adverse Effects (CTCAE)3.0.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: September 2013
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Digestive System Neoplasms
• Gastric Cancer
• Gastrointestinal Neoplasms
• Stomach Neoplasms

Intervention

Drug:
• S-1
S-1,30mg/m2/d,peroral BID,in treatment days concurrently with radiation therapy in a standard manner.
• S-1
S-1,40mg/m2/d,peroral BID,in treatment days concurrently with radiation therapy in a standard manner.
• S-1
S-1,50mg/m2/d,peroral BID,in treatment days concurrently with radiation therapy in a standard manner
• S-1
S-1,60mg/m2/d,peroral BID,in treatment days concurrently with radiation therapy in a standard manner.
• S-1
S-1,70mg/m2/d,peroral BID,in treatment days concurrently with radiation therapy in a standard manner.
• S-1
S-1,80mg/m2/d,peroral BID,in treatment days concurrently with radiation therapy in a standard manner.

Locations

Country	Name	City	State
China	Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Chinese Academy of Medical Sciences

Country where clinical trial is conducted

China, 

References & Publications (12)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Parkin DM, Pisani P, Ferlay J. Global cancer statistics. CA Cancer J Clin. 1999 Jan-Feb;49(1):33-64, 1. — View Citation

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. Epub 2007 Nov 8. — View Citation

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. — View Citation

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. Erratum in: N Engl J Med. 2008 May 1;358(18):1977. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	To define maximum tolerated dose(MTD) of S-1, peroral BID, in treatment days concurrently with radiation therapy	If 1 of 3 patients treated within a S-1 dose level experiences DLTs, 3 more patients will be treated at the same level. If a second patient experiences DLTs, then escalation will be stopped and the MTD is defined as the level below DLT dose level.	up to 9 weeks