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

NYU Langone Health

Status and phase: Completed; Phase 2

Conditions: Gastric Cancer; Stomach Cancer

Treatments: Drug: Cetuximab; Procedure: Surgery; Radiation: Radiation; Drug: Cisplatin; Drug: Irinotecan; Drug: 5-FU

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00857246

BMS #CA225112 (Other Identifier)

04-72 (H12637)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 30 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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30 participants in 1 patient group

Induction/ surgery/ chemoRT

Experimental group

Description:

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

Treatment:

Radiation: Radiation

Procedure: Surgery

Drug: 5-FU

Drug: Irinotecan

Drug: Cisplatin

Drug: Cetuximab