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

Primary Purpose

Gastrointestinal Neoplasms, Gastric Cancer

Status
Completed
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
S-1
S-1
S-1
S-1
S-1
S-1
Sponsored by
Chinese Academy of Medical Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastrointestinal Neoplasms focused on measuring Combined Modality, Gastric Cancer, Radiation Therapy, S-1

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

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

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

S-1,peroral BID,capsule

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

First Posted
February 7, 2011
Last Updated
September 17, 2013
Sponsor
Chinese Academy of Medical Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT01291407
Brief Title
A Phase I Study of S-1 in Combination With Radiotherapy in Locally Advanced or Recurrent Gastric Cancer
Official Title
A Phase I Study of S-1 in Combination With Radiotherapy in Locally Advanced or Recurrent Gastric Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
September 2013
Overall Recruitment Status
Completed
Study Start Date
November 2010 (undefined)
Primary Completion Date
August 2013 (Actual)
Study Completion Date
September 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Chinese Academy of Medical Sciences

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastrointestinal Neoplasms, Gastric Cancer
Keywords
Combined Modality, Gastric Cancer, Radiation Therapy, S-1

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
27 (Actual)

8. Arms, Groups, and Interventions

Arm Title
S-1,peroral BID,capsule
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
S-1
Other Intervention Name(s)
an oral fluorinated pyrimidine combination
Intervention Description
S-1,30mg/m2/d,peroral BID,in treatment days concurrently with radiation therapy in a standard manner.
Intervention Type
Drug
Intervention Name(s)
S-1
Other Intervention Name(s)
an oral fluorinated pyrimidine combination
Intervention Description
S-1,40mg/m2/d,peroral BID,in treatment days concurrently with radiation therapy in a standard manner.
Intervention Type
Drug
Intervention Name(s)
S-1
Other Intervention Name(s)
an oral fluorinated pyrimidine combination
Intervention Description
S-1,50mg/m2/d,peroral BID,in treatment days concurrently with radiation therapy in a standard manner
Intervention Type
Drug
Intervention Name(s)
S-1
Other Intervention Name(s)
an oral fluorinated pyrimidine combination
Intervention Description
S-1,60mg/m2/d,peroral BID,in treatment days concurrently with radiation therapy in a standard manner.
Intervention Type
Drug
Intervention Name(s)
S-1
Other Intervention Name(s)
an oral fluorinated pyrimidine combination
Intervention Description
S-1,70mg/m2/d,peroral BID,in treatment days concurrently with radiation therapy in a standard manner.
Intervention Type
Drug
Intervention Name(s)
S-1
Other Intervention Name(s)
an oral fluorinated pyrimidine combination
Intervention Description
S-1,80mg/m2/d,peroral BID,in treatment days concurrently with radiation therapy in a standard manner.
Primary Outcome Measure Information:
Title
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.
Description
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.
Time Frame
up to 9 weeks
Secondary Outcome Measure Information:
Title
To define maximum tolerated dose(MTD) of S-1, peroral BID, in treatment days concurrently with radiation therapy
Description
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.
Time Frame
up to 9 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jing Jin, MD,PhD
Organizational Affiliation
Department of Radiation Oncology,Cancer Hospital and Institute,CAMS
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Yexiong Li, MD,PhD
Organizational Affiliation
Department of Radiation Oncology,Cancer Hospital and Institute, CAMS
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)
City
Beijing
ZIP/Postal Code
100021
Country
China

12. IPD Sharing Statement

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

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