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 (Responsible Party):
New York University School of Medicine
ClinicalTrials.gov Identifier:
NCT00857246
First received: March 4, 2009
Last updated: March 2, 2015
Last verified: March 2015
  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
Drug: Irinotecan
Drug: Cisplatin
Procedure: Surgery
Drug: 5-FU
Radiation: Radiation
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 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 ]
    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:
  • Rate of Clearance of Nodal Involvement Among Patients Who Have Received the Induction Therapy [ Time Frame: 4 months from the beginning of the induction treatment ] [ Designated as safety issue: No ]
    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 [ Time Frame: 4 months from the beginning of the induction treatment ] [ Designated as safety issue: No ]
    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 [ Time Frame: 4 months from the beginning of the induction treatment ] [ Designated as safety issue: No ]
    This is defined as the percentage of patients who had a reduction from T3/T4 disease.

  • Safety of the Induction Regimen [ Time Frame: 4 months from the beginning of the induction ] [ Designated as safety issue: Yes ]
    This describes the number of patients who experienced grade 3 and higher adverse events related to the regimen.

  • Median Overall Survival (Induction Treatment and Curative Surgery) [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
    This is the length of time from the start of treatment that half of the patients are still alive.

  • Median Overall Survival (Adjuvant Therpary) [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
    This is the length of time from the start of treatment that half of the patients are still alive.


Enrollment: 30
Study Start Date: July 2005
Estimated Study Completion Date: June 2015
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Induction/ surgery/ chemoRT
  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

Drug: Cetuximab
Other Name: Erbitux
Drug: Irinotecan
Other Names:
  • CPT-11
  • Camptosar
Drug: Cisplatin
Other Name: Platinol-AQ
Procedure: Surgery Drug: 5-FU
Other Name: Fluorourocil
Radiation: Radiation

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.

  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 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).
  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: New York University School of Medicine
ClinicalTrials.gov Identifier: NCT00857246     History of Changes
Other Study ID Numbers: 04-72 (H12637), BMS #CA225112
Study First Received: March 4, 2009
Results First Received: March 2, 2015
Last Updated: March 2, 2015
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
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Neoplasms
Neoplasms by Site
Stomach Diseases
Cetuximab
Cisplatin
Irinotecan
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Radiation-Sensitizing Agents
Therapeutic Uses
Topoisomerase I Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on July 30, 2015