Gastric Adenocarcinoma, Stage II Gastric Cancer, Stage III Gastric Cancer, Stage IV Gastric Cancer
Conditions
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.
Interventions
DRUGCisplatin
Given IV
PROCEDUREComputed Tomography
Undergo FDG and FLT PET/CT
RADIATIONFludeoxyglucose F-18
Undergo FDG-PET/CT
OTHERFluorothymidine F-18
Undergo FLT-PET/CT
DRUGIrinotecan Hydrochloride
Given IV
PROCEDUREPositron Emission Tomography
Undergo FDG and FLT PET/CT
PROCEDURETherapeutic Conventional Surgery
Undergo radical subtotal or total gastrectomy with lymph node dissection
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Histological Response Determined by FDG Uptake Correlates | Day 15 | 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) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Disease Free Survival (DFS) | Every 3 mos for the first 2 yrs, then every 6 mos for 2 years and once a year afterwards, up to 5 years | 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. |
Countries
United States
Participant flow
Recruitment details
Date Opened to Accrual: 6/5/2003 Date Closed to Accrual: 8/8/2006 Date Closed: 6/28/2011 Recruitment location is the medical clinic
Participants by arm
| Arm | Count |
|---|---|
| Arm I 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.
irinotecan hydrochloride: Given IV
cisplatin: Given IV
conventional surgery: Undergo radical subtotal or total gastrectomy with lymph node dissection
positron emission tomography/computed tomography: Undergo FDG-PET/CT
fludeoxyglucose F 18: Undergo FDG-PET/CT
positron emission tomography/computed tomography: Undergo FLT-PET/CT
fluorine F 18 fluorothymidine: Undergo FLT-PET/CT | 55 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Not treated | 12 |
Baseline characteristics
| Characteristic | Arm I |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 20 Participants |
| Age, Categorical Between 18 and 65 years | 35 Participants |
| Region of Enrollment United States | 55 participants |
| Sex: Female, Male Female | 23 Participants |
| Sex: Female, Male Male | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 44 / 55 |
| serious Total, serious adverse events | 14 / 55 |
Outcome results
Primary
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)
Time frame: Day 15
Population: Technical problems with measurement of FDG-SUV data leading to unreliable or uninterpretable data. Data adjudication was invalid, and needs to be re-adjudicated. Therefore, only histological response is reported.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm I | Histological Response Determined by FDG Uptake Correlates | Progression of Disease | 2 participants |
| Arm I | Histological Response Determined by FDG Uptake Correlates | Responders | 3 participants |
| Arm I | Histological Response Determined by FDG Uptake Correlates | Non-Responders | 38 participants |
Other Pre-specified
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.
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
Population: Technical problems with measurement leading to unreliable or uninterpretable data. Data adjudication was invalid, and needs to be re-adjudicated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I | Disease Free Survival (DFS) | 23.8 months |