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

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

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.

Study Overview

• Status: Completed
• Conditions: Gastric Adenocarcinoma; Stage IV Gastric Cancer; Stage II Gastric Cancer; Stage III Gastric Cancer
• Intervention / Treatment: Drug: Cisplatin; Drug: Irinotecan Hydrochloride; Radiation: Fludeoxyglucose F-18; Procedure: Computed Tomography; Other: Fluorothymidine F-18; Procedure: Positron Emission Tomography; Procedure: Therapeutic Conventional 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.

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (preoperative chemotherapy); 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.

Drug: Cisplatin; Given IV; Other Names: CDDP; Cis-diamminedichloridoplatinum; Cismaplat; Cisplatinum; Neoplatin; Platinol; Abiplatin; Blastolem; Briplatin; Cis-diammine-dichloroplatinum; Cis-diamminedichloro Platinum (II); Cis-diamminedichloroplatinum; Cis-dichloroammine Platinum (II); Cis-platinous Diamine Dichloride; Cis-platinum; Cis-platinum II; Cis-platinum II Diamine Dichloride; Cisplatina; Cisplatyl; Citoplatino; Citosin; Cysplatyna; DDP; Lederplatin; Metaplatin; Peyrone's Chloride; Peyrone's Salt; Placis; Plastistil; Platamine; Platiblastin; Platiblastin-S; Platinex; Platinol- AQ; Platinol-AQ; Platinol-AQ VHA Plus; Platinoxan; Platinum; Platinum Diamminodichloride; Platiran; Platistin; Platosin; Drug: Irinotecan Hydrochloride; Given IV; Other Names: Campto; Camptosar; U-101440E; CPT-11; Camptothecin 11; Camptothecin-11; CPT 11; Irinomedac; Radiation: Fludeoxyglucose F-18; Undergo FDG-PET/CT; Other Names: 18FDG; FDG; fludeoxyglucose F 18; Fludeoxyglucose F18; Fluorine-18 2-Fluoro-2-deoxy-D-Glucose; Fluorodeoxyglucose F18; Procedure: Computed Tomography; Undergo FDG and FLT PET/CT; Other Names: CT; CAT; CAT Scan; Computerized Axial Tomography; Computerized Tomography; tomography; CT SCAN; Other: Fluorothymidine F-18; Undergo FLT-PET/CT; Other Names: 18F-FLT; 3'-deoxy-3'-[18F]fluorothymidine; 3'-Deoxy-3'-(18F) Fluorothymidine; Fluorothymidine F 18; Procedure: Positron Emission Tomography; Undergo FDG and FLT PET/CT; Other Names: Medical Imaging, Positron Emission Tomography; PET; Positron Emission Tomography Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; PET SCAN; Procedure: Therapeutic Conventional Surgery; Undergo radical subtotal or total gastrectomy with lymph node dissection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Day 15

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Free Survival (DFS)	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.	Every 3 mos for the first 2 yrs, then every 6 mos for 2 years and once a year afterwards, up to 5 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Manisha Shah, Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start: June 1, 2003
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: June 5, 2003
• First Submitted That Met QC Criteria: June 5, 2003
• First Posted (Estimate): June 6, 2003

Study Record Updates

• Last Update Posted (Actual): July 6, 2017
• Last Update Submitted That Met QC Criteria: June 7, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Topoisomerase Inhibitors; Radiopharmaceuticals; Topoisomerase I Inhibitors; Fluorodeoxyglucose F18; Cisplatin; Irinotecan; Alovudine; Camptothecin; Deoxyglucose
• Other Study ID Numbers: NCI-2012-01438 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); P30CA008748 (U.S. NIH Grant/Contract); NCI-5917; CDR0000304738; MSKCC-03032; 03-032 (Other Identifier: Memorial Sloan-Kettering Cancer Center); 5917 (Other Identifier: CTEP)