Pre-operation Chemo and Antibody Therapy Followed by Surgical Resection and Adjuvant Chemoradiation for Gastric Cancer

Phase 2

Completed

Conditions: Gastric Cancer
Stomach Cancer

Interventions: Drug: Cetuximab
Drug: Irinotecan
Drug: Cisplatin
Procedure: Surgery
Drug: 5-FU
Radiation: Radiation

Registration Number: NCT00857246

Lead Sponsor: NYU Langone Health

Brief Summary: This study intends to evaluate the feasibility and treatment efficacy of adding an antibody blocking the epidermal growth factor (EGF) pathway to a neoadjuvant approach with proven efficacy developed at New York University.

Detailed Description: The overall objective of this study is the development of definitive treatments for patients with locally advanced gastric cancer. To this end, this trial is evaluating the feasibility and treatment efficacy of adding an antibody blocking the EGF pathway to a neoadjuvant approach with proven efficacy developed at New York University (NYU). The combination of Irinotecan and Cisplatin has been shown to be synergistic and active against gastric carcinoma. This trial therefore builds upon NYU previous experience with the neoadjuvant administration of Irinotecan combined with Cisplatin as well as the reported enhanced activity of Irinotecan, Cisplatin and External beam radiation when combined with Cetuximab to develop a novel neoadjuvant and adjuvant approach for the treatment of gastric and gastro-esophageal junction (GEJ) cancers. The program includes: 1) systemic combination of Irinotecan, Cisplatin and Cetuximab used as an induction, 2) followed by potentially curative gastrectomy or GEJ resection, and 3) post-operative chemoradiation as reported in the Intergroup study with the addition of Cetuximab.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 30

Inclusion Criteria

Patients must have signed an approved informed consent.
must have histologically documented untreated gastric/GEJ carcinoma (clinical stage T3 N0 or T4, or any T with N1-N3 M0)
Patients with tumor tissue available for assessment of EGF receptor status by immuno-histochemistry (IHC).
Patients with Performance Status 0-2.
Patients, 18 years and older, must either be not of child bearing potential or have a negative pregnancy test within 7 days of treatment. Patients are considered not of child bearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal.
Bone marrow function: absolute neutrophil count (ANC) at least 1,500/ul; platelets at least 100,000/ul.
Renal function: creatinine not greater than 1.5 x institutional upper limit of normal (ULN).
The PT and PTT should be within the range of normal values
Hepatic function: bilirubin not greater than 1.5 x ULN; aspartate aminotransferase (AST) not greater than 2.5 x ULN.

Exclusion Criteria

Acute hepatitis or known HIV.
Active or uncontrolled infection.
Significant history of uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, and congestive heart failure.
Prior therapy that affects or targets the EGF pathway.
Prior allergic reaction to chimerized or murine monoclonal antibody therapy or documented presence of human anti-mouse antibodies (HAMA).
Any concurrent chemotherapy not indicated in the study protocol or any other investigational agent(s).

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Induction/ surgery/ chemoRT	Surgery	1. Induction treatment (3 weeks/cycle x 4 cycles): Cisplatin and Irinotecan on days 1 and 8; Cetuximab on days 1, 8, and 15. 2. Surgery (starts 3-4 weeks after induction treatment). 3. Chemoradiation treatment (starts 4-6 weeks after surgery): weeks 1-19: Cetuximab on day 1 of every week; week 1: 5-FU and Leucovorin (LV) x 5 days; weeks 2-4: recovery; weeks 5-9: radiation, 150 cGy x 5 fractions/week x 5 weeks; week 5: 5-FU+ LV on days 1-4; week 9: 5-FU+ LV on days 1-3; weeks 14 and 19: 5-FU+LV x 5days
Induction/ surgery/ chemoRT	Radiation	1. Induction treatment (3 weeks/cycle x 4 cycles): Cisplatin and Irinotecan on days 1 and 8; Cetuximab on days 1, 8, and 15. 2. Surgery (starts 3-4 weeks after induction treatment). 3. Chemoradiation treatment (starts 4-6 weeks after surgery): weeks 1-19: Cetuximab on day 1 of every week; week 1: 5-FU and Leucovorin (LV) x 5 days; weeks 2-4: recovery; weeks 5-9: radiation, 150 cGy x 5 fractions/week x 5 weeks; week 5: 5-FU+ LV on days 1-4; week 9: 5-FU+ LV on days 1-3; weeks 14 and 19: 5-FU+LV x 5days
Induction/ surgery/ chemoRT	Cetuximab	1. Induction treatment (3 weeks/cycle x 4 cycles): Cisplatin and Irinotecan on days 1 and 8; Cetuximab on days 1, 8, and 15. 2. Surgery (starts 3-4 weeks after induction treatment). 3. Chemoradiation treatment (starts 4-6 weeks after surgery): weeks 1-19: Cetuximab on day 1 of every week; week 1: 5-FU and Leucovorin (LV) x 5 days; weeks 2-4: recovery; weeks 5-9: radiation, 150 cGy x 5 fractions/week x 5 weeks; week 5: 5-FU+ LV on days 1-4; week 9: 5-FU+ LV on days 1-3; weeks 14 and 19: 5-FU+LV x 5days
Induction/ surgery/ chemoRT	Cisplatin	1. Induction treatment (3 weeks/cycle x 4 cycles): Cisplatin and Irinotecan on days 1 and 8; Cetuximab on days 1, 8, and 15. 2. Surgery (starts 3-4 weeks after induction treatment). 3. Chemoradiation treatment (starts 4-6 weeks after surgery): weeks 1-19: Cetuximab on day 1 of every week; week 1: 5-FU and Leucovorin (LV) x 5 days; weeks 2-4: recovery; weeks 5-9: radiation, 150 cGy x 5 fractions/week x 5 weeks; week 5: 5-FU+ LV on days 1-4; week 9: 5-FU+ LV on days 1-3; weeks 14 and 19: 5-FU+LV x 5days
Induction/ surgery/ chemoRT	Irinotecan	1. Induction treatment (3 weeks/cycle x 4 cycles): Cisplatin and Irinotecan on days 1 and 8; Cetuximab on days 1, 8, and 15. 2. Surgery (starts 3-4 weeks after induction treatment). 3. Chemoradiation treatment (starts 4-6 weeks after surgery): weeks 1-19: Cetuximab on day 1 of every week; week 1: 5-FU and Leucovorin (LV) x 5 days; weeks 2-4: recovery; weeks 5-9: radiation, 150 cGy x 5 fractions/week x 5 weeks; week 5: 5-FU+ LV on days 1-4; week 9: 5-FU+ LV on days 1-3; weeks 14 and 19: 5-FU+LV x 5days
Induction/ surgery/ chemoRT	5-FU	1. Induction treatment (3 weeks/cycle x 4 cycles): Cisplatin and Irinotecan on days 1 and 8; Cetuximab on days 1, 8, and 15. 2. Surgery (starts 3-4 weeks after induction treatment). 3. Chemoradiation treatment (starts 4-6 weeks after surgery): weeks 1-19: Cetuximab on day 1 of every week; week 1: 5-FU and Leucovorin (LV) x 5 days; weeks 2-4: recovery; weeks 5-9: radiation, 150 cGy x 5 fractions/week x 5 weeks; week 5: 5-FU+ LV on days 1-4; week 9: 5-FU+ LV on days 1-3; weeks 14 and 19: 5-FU+LV x 5days

Primary Outcome Measures

Name	Time	Method
Clinical Response Rate of an Induction Regimen Consisting of Irinotecan, Cisplatin and Cetuximab	4 months from the beginning of the induction regimen	Clinical response rate is defined as the percentage of patients who responded to the induction regimen. The response is determined based on endoscopic ultrasonography (EUS) staging pre-treatment and post-treatment, CT scans pre- and post- operatively, and initial clinical stage (based on these tests) compared with the pathologic stage. Any "down-staging" of T or N stage is considered to be a result of induction therapy and counted as a clinical response.

Secondary Outcome Measures

Name	Time	Method
Median Overall Survival (Induction Treatment and Curative Surgery)	up to 5 years	This is the length of time from the start of treatment that half of the patients are still alive.
Median Overall Survival (Adjuvant Therpary)	up to 5 years	This is the length of time from the start of treatment that half of the patients are still alive.
Rate of Clearance of Nodal Involvement Among Patients Who Have Received the Induction Therapy	4 months from the beginning of the induction treatment	This is defined as the percentage of patients whose nodal involvement of cancer has been cleared based on surgery results.
Rate of Potentially Curative Surgery	4 months from the beginning of the induction treatment	This is defined as the percentage of patients who underwent curative surgery (surgery to remove all cancerous tissue).
Rate of "Down-staging" From Pre-operative Clinical Staging	4 months from the beginning of the induction treatment	This is defined as the percentage of patients who had a reduction from T3/T4 disease.
Safety of the Induction Regimen	4 months from the beginning of the induction	This describes the number of patients who experienced grade 3 and higher adverse events related to the regimen.