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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Bristol-Myers Squibb
ImClone LLC
Information provided by:
New York University School of Medicine
ClinicalTrials.gov Identifier:
NCT00857246
First received: March 4, 2009
Last updated: May 7, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Gastric Cancer
Stomach Cancer
Drug: Cetuximab/ Irinotecan/ Cisplatin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Neoadjuvant Therapy of Gastric Cancer With Irinotecan, Cisplatin and Cetuximab Followed by Surgical Resection and Adjuvant Chemoradiation

Resource links provided by NLM:


Further study details as provided by New York University School of Medicine:

Primary Outcome Measures:
  • clinical response rate (RR) of an induction regimen consisting of Irinotecan, Cisplatin and Cetuximab [ Time Frame: 4 months from the beginning of the induction regimen ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • rate of clearance of nodal involvement; rate of potentially curative surgery among patients who have received the induction therapy; rate of "down-staging" from pre-operative clinical staging [ Time Frame: up to 1 year from the beginning of the induction treatment ] [ Designated as safety issue: No ]
  • safety of the regimen [ Time Frame: 1 year after the start of first treatment and every year afterwards ] [ Designated as safety issue: Yes ]
  • overall survival [ Time Frame: every 4 months for the 1st year, every 6 months for the 2nd and 3rd year, every 12 months thereafter for a total 5 years ] [ Designated as safety issue: No ]

Enrollment: 30
Study Start Date: July 2005
Estimated Study Completion Date: December 2014
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Induction chemo/ surgery/ chemoRT Drug: Cetuximab/ Irinotecan/ Cisplatin
  1. Induction treatment (3 weeks/cycle x 4 cycles):

    Day 1, 8: Cisplatin 25 mg/m^2, Irinotecan 75 mg/m^2. Day 1, 8, 15: Cetuximab 400 mg/m^2 initial dose, then 250 mg/m^2 weekly.

  2. Surgery (3-4 weeks after induction treatment).
  3. Chemoradiation treatment (4-6 weeks after surgery):

weeks 1-19: Cetuximab 250 mg/m^2 weekly on day 1 of every week; week 1: 5-FU 425 mg/m^2/day x 5 days + Leucovorin (LV) 20 mg/m^2/day x 5days; weeks 2-4: recovery; weeks 5-9: radiation, 150 cGy x 5 fractions/week x 5 weeks; week 5: 5-FU 400 mg/m^2 + LV 20 mg/m^2 each day on days 1-4; week 9: 5-FU 400 mg/m^2 + LV 20 mg/m^2 each day on days 1-3; week 14: 5-FU 425 mg/m^2/day x 5 days + Leucovorin (LV) 20 mg/m^2/day x 5days; week 19: 5-FU 425 mg/m^2/day x 5 days + Leucovorin (LV) 20 mg/m^2/day x 5days.

Other Names:
  • Cetuximab: Erbitux
  • Irinotecan: CPT-11
  • Irinotecan: Camptosar
  • Cisplatin: Platinol-AQ

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. The combination of Irinotecan and Cisplatin has been shown to be synergistic and active against gastric carcinoma. This trial therefore builds upon our 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 esophago-gastric 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 EGFR status by 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; 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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00857246

Locations
United States, New York
NYU Cancer Center
New York, New York, United States, 10016
Sponsors and Collaborators
New York University School of Medicine
Bristol-Myers Squibb
ImClone LLC
Investigators
Principal Investigator: Theresa Ryan, MD New York University School of Medicine
  More Information

No publications provided

Responsible Party: Theresa Ryan, MD, NYU Cancer Institute
ClinicalTrials.gov Identifier: NCT00857246     History of Changes
Other Study ID Numbers: 04-72 (H12637), BMS #CA225112
Study First Received: March 4, 2009
Last Updated: May 7, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by New York University School of Medicine:
stomach cancer
biologics
antibody
chemotherapy
chemoradiation
adjuvant therapy
neoadjuvant therapy
epidermal growth factor receptor
combination therapy

Additional relevant MeSH terms:
Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Irinotecan
Cetuximab
Cisplatin
Camptothecin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antineoplastic Agents, Phytogenic
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 20, 2014