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Irinotecan and Cisplatin in Treating Patients Who Are Undergoing Surgery For Locally Advanced Cancer of the Stomach or Gastroesophageal Junction

Primary Purpose

Gastric Adenocarcinoma, Stage II Gastric Cancer, Stage III Gastric Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Cisplatin
Computed Tomography
Fludeoxyglucose F-18
Fluorothymidine F-18
Irinotecan Hydrochloride
Positron Emission Tomography
Therapeutic Conventional Surgery
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastric Adenocarcinoma

Eligibility Criteria

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

Inclusion Criteria: All patients must have microscopically confirmed adenocarcinoma of the stomach or gastroesophageal (GE) junction with material reviewed by the Department of Pathology of the participating Institution; tumors involving the GE junction must have the bulk of their disease in the stomach; tumors of the distal esophagus that extend less than 2cm into the stomach are ineligible for this study; using the Siewert's classification for the GE junction, tumors designated as Types II and III are indeed considered eligible for this clinical trial All patients must have localized cancer potentially curable by surgery; the tumor stage should be Tany N+ M0 or T3-T4 Nany M0, by staging that includes a computed tomography (CT) scan and either laparoscopy-assisted pancreatobiliary (LAP) or endoscopic ultrasound (EUS); patients with T1-2N0M0 tumors, confirmed by LAP ("good risk") are ineligible; any sites of suspected M1 disease by these criteria must be proven to be M0 prior to entrance into a neoadjuvant trial Patients must have a Karnofsky Performance Status >= 60% (Eastern Cooperative Oncology Group [ECOG] =< 2) and be able to tolerate the proposed surgical procedure and chemotherapy regimen Patients may not have received prior chemotherapy or radiation for this disease Absolute neutrophil count (ANC) >= 1,500 cells/mm^3 Platelets >= 100,000/mm^3 Serum creatinine =< 1.5 mg/dL Total serum bilirubin =< 1.5 mg/dL Patients must have signed informed consent indicating that they are aware of the investigational nature of the study and that participation is voluntary No clinically significant auditory impairment No clinically significant peripheral neuropathy New York Heart Association (NYHA) class I-II Patients must not have a prior history of cancer within the last five years except for non-melanoma skin cancer, non-metastatic prostate cancer or carcinoma in situ of the uterine cervix Exclusion Criteria: Any metastatic disease NYHA Class III or IV heart disease; history of active angina or myocardial infarction within 6 months; history of significant ventricular arrhythmia requiring medication with antiarrhythmics or a history of a clinically significant conduction system abnormality Pregnant or lactating women are ineligible; fertile men and women, unless using effective contraception, are ineligible; a pregnancy test will be performed on sexually active women of childbearing potential prior to entry into the study; treatment may not begin until the results of the pregnancy test are ascertained Serious intercurrent infections, or nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this therapy Grade 2 or greater pre-existing peripheral neuropathy Psychiatric disorders rendering patients incapable of complying with the requirements of the protocol Any concurrent active malignancy other than non-melanoma skin cancers, non-metastatic prostate cancer or carcinoma-in-situ of the uterine cervix; patients with previous malignancies but without evidence of disease for > 5 years will be allowed to enter the trial Clinically significant hearing loss

Sites / Locations

  • Memorial Sloan-Kettering Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (preoperative chemotherapy)

Arm Description

Neoadjuvant chemotherapy: Patients receive cisplatin IV over 30 minutes followed by irinotecan IV over 30 minutes on days 1, 8, 22, and 29. Treatment repeats every 6 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Surgery: Within 4 weeks after completion of neoadjuvant chemotherapy, patients undergo radical subtotal or total gastrectomy with lymph node dissection.

Outcomes

Primary Outcome Measures

Histological Response Determined by FDG Uptake Correlates
The primary objective was to demonstrate that a decrease in FDG-SUV discriminates treatment response. Response was defined pathologically based on microscopic inspection for residual cancer cells and fibrosis. Using a two sample t-test, we would be able to adequately test that the decrease in SUV early in the treatment plan is significantly different between responders and non responders. Data adjudication was invalid, and needs to be re-adjudicated Non-Responder= Tumor Regression Grade 3 or higher Responder=Tumor Regression Grade 1 (CR) or Grade 2 (PR)

Secondary Outcome Measures

Full Information

First Posted
June 5, 2003
Last Updated
June 7, 2017
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00062374
Brief Title
Irinotecan and Cisplatin in Treating Patients Who Are Undergoing Surgery For Locally Advanced Cancer of the Stomach or Gastroesophageal Junction
Official Title
An Evaluation of Preoperative Chemotherapy With Irinotecan and Cisplatin for Advanced, But Resectable Gastric Cancer: A Coordinated Multidisciplinary, Multicenter Study Linking Functional Imaging, Genomic Expression Profiles and Histopathology
Study Type
Interventional

2. Study Status

Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
June 2003 (undefined)
Primary Completion Date
June 2011 (Actual)
Study Completion Date
June 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
This phase II trial is studying how well giving irinotecan together with cisplatin works in treating patients who are undergoing surgical resection for locally advanced cancer of the stomach or gastroesophageal junction. Drugs used in chemotherapy, such as irinotecan and cisplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one chemotherapy drug and giving them before surgery may shrink the tumor so that it can be removed during surgery.
Detailed Description
PRIMARY OBJECTIVES: I. To evaluate the correlation of fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) imaging early in the preoperative treatment program of locally advanced gastric cancer with histologic response assessment and patient outcome, defined as overall and progression-free survival. SECONDARY OBJECTIVES: I. To evaluate the efficacy and safety of preoperative chemotherapy with irinotecan and cisplatin in the treatment of locally advanced gastric cancer. II. To examine the biology of locally advanced gastric cancer and the response to chemotherapy by DNA microarray technology and by histopathology. III. To obtain preliminary data on biodistribution, dosimetry and explore the potential clinical usefulness of fluorodeoxythymidine (FLT) PET in patients with locally advanced gastric cancer undergoing a novel combination neoadjuvant chemotherapy. OUTLINE: This is an open-label, nonrandomized, multicenter study. Neoadjuvant chemotherapy: Patients receive cisplatin intravenously (IV) over 30 minutes followed by irinotecan IV over 30 minutes on days 1, 8, 22, and 29. Treatment repeats every 6 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Surgery: Within 4 weeks after completion of neoadjuvant chemotherapy, patients undergo radical subtotal or total gastrectomy with lymph node dissection. Patients undergo fluorodeoxyglucose FDG-PET/CT at baseline. Some patients undergo additional FDG-PET/CT scans in weeks 3 and 6. Approximately 5 patients undergo fluorothymidine FLT-PET/CT at baseline, during week 3, and/or before surgical resection. Patients are followed up every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastric Adenocarcinoma, Stage II Gastric Cancer, Stage III Gastric Cancer, Stage IV Gastric Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
55 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (preoperative chemotherapy)
Arm Type
Experimental
Arm Description
Neoadjuvant chemotherapy: Patients receive cisplatin IV over 30 minutes followed by irinotecan IV over 30 minutes on days 1, 8, 22, and 29. Treatment repeats every 6 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Surgery: Within 4 weeks after completion of neoadjuvant chemotherapy, patients undergo radical subtotal or total gastrectomy with lymph node dissection.
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Other Intervention Name(s)
Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
Computed Tomography
Other Intervention Name(s)
CAT, CAT Scan, Computerized Axial Tomography, Computerized Tomography, CT, CT SCAN, tomography
Intervention Description
Undergo FDG and FLT PET/CT
Intervention Type
Radiation
Intervention Name(s)
Fludeoxyglucose F-18
Other Intervention Name(s)
18FDG, FDG, fludeoxyglucose F 18, Fludeoxyglucose F18, Fluorine-18 2-Fluoro-2-deoxy-D-Glucose, Fluorodeoxyglucose F18
Intervention Description
Undergo FDG-PET/CT
Intervention Type
Other
Intervention Name(s)
Fluorothymidine F-18
Other Intervention Name(s)
18F-FLT, 3'-Deoxy-3'-(18F) Fluorothymidine, 3'-deoxy-3'-[18F]fluorothymidine, Fluorothymidine F 18
Intervention Description
Undergo FLT-PET/CT
Intervention Type
Drug
Intervention Name(s)
Irinotecan Hydrochloride
Other Intervention Name(s)
Campto, Camptosar, Camptothecin 11, Camptothecin-11, CPT 11, CPT-11, Irinomedac, U-101440E
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
Positron Emission Tomography
Other Intervention Name(s)
Medical Imaging, Positron Emission Tomography, PET, PET SCAN, Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging
Intervention Description
Undergo FDG and FLT PET/CT
Intervention Type
Procedure
Intervention Name(s)
Therapeutic Conventional Surgery
Intervention Description
Undergo radical subtotal or total gastrectomy with lymph node dissection
Primary Outcome Measure Information:
Title
Histological Response Determined by FDG Uptake Correlates
Description
The primary objective was to demonstrate that a decrease in FDG-SUV discriminates treatment response. Response was defined pathologically based on microscopic inspection for residual cancer cells and fibrosis. Using a two sample t-test, we would be able to adequately test that the decrease in SUV early in the treatment plan is significantly different between responders and non responders. Data adjudication was invalid, and needs to be re-adjudicated Non-Responder= Tumor Regression Grade 3 or higher Responder=Tumor Regression Grade 1 (CR) or Grade 2 (PR)
Time Frame
Day 15
Other Pre-specified Outcome Measures:
Title
Disease Free Survival (DFS)
Description
Overall Survival (OS) and Disease Free Survival (DFS) are the secondary endpoints. Technical problems with measurement of OS leading to unreliable or uniterpretable data. Data adjudication was invalid, and needs to be re-adjudicated. Therefore, only DFS data is being reported.
Time Frame
Every 3 mos for the first 2 yrs, then every 6 mos for 2 years and once a year afterwards, up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: All patients must have microscopically confirmed adenocarcinoma of the stomach or gastroesophageal (GE) junction with material reviewed by the Department of Pathology of the participating Institution; tumors involving the GE junction must have the bulk of their disease in the stomach; tumors of the distal esophagus that extend less than 2cm into the stomach are ineligible for this study; using the Siewert's classification for the GE junction, tumors designated as Types II and III are indeed considered eligible for this clinical trial All patients must have localized cancer potentially curable by surgery; the tumor stage should be Tany N+ M0 or T3-T4 Nany M0, by staging that includes a computed tomography (CT) scan and either laparoscopy-assisted pancreatobiliary (LAP) or endoscopic ultrasound (EUS); patients with T1-2N0M0 tumors, confirmed by LAP ("good risk") are ineligible; any sites of suspected M1 disease by these criteria must be proven to be M0 prior to entrance into a neoadjuvant trial Patients must have a Karnofsky Performance Status >= 60% (Eastern Cooperative Oncology Group [ECOG] =< 2) and be able to tolerate the proposed surgical procedure and chemotherapy regimen Patients may not have received prior chemotherapy or radiation for this disease Absolute neutrophil count (ANC) >= 1,500 cells/mm^3 Platelets >= 100,000/mm^3 Serum creatinine =< 1.5 mg/dL Total serum bilirubin =< 1.5 mg/dL Patients must have signed informed consent indicating that they are aware of the investigational nature of the study and that participation is voluntary No clinically significant auditory impairment No clinically significant peripheral neuropathy New York Heart Association (NYHA) class I-II Patients must not have a prior history of cancer within the last five years except for non-melanoma skin cancer, non-metastatic prostate cancer or carcinoma in situ of the uterine cervix Exclusion Criteria: Any metastatic disease NYHA Class III or IV heart disease; history of active angina or myocardial infarction within 6 months; history of significant ventricular arrhythmia requiring medication with antiarrhythmics or a history of a clinically significant conduction system abnormality Pregnant or lactating women are ineligible; fertile men and women, unless using effective contraception, are ineligible; a pregnancy test will be performed on sexually active women of childbearing potential prior to entry into the study; treatment may not begin until the results of the pregnancy test are ascertained Serious intercurrent infections, or nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this therapy Grade 2 or greater pre-existing peripheral neuropathy Psychiatric disorders rendering patients incapable of complying with the requirements of the protocol Any concurrent active malignancy other than non-melanoma skin cancers, non-metastatic prostate cancer or carcinoma-in-situ of the uterine cervix; patients with previous malignancies but without evidence of disease for > 5 years will be allowed to enter the trial Clinically significant hearing loss
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Manisha Shah
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Irinotecan and Cisplatin in Treating Patients Who Are Undergoing Surgery For Locally Advanced Cancer of the Stomach or Gastroesophageal Junction

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