Clinical trial NCT00857246: Pre-operation Chemo and Antibody Therapy Followed by Surgical Resection and Adjuvant Chemoradiation for Gastric Cancer
Official title: Neoadjuvant Therapy of Gastric Cancer With Irinotecan, Cisplatin and Cetuximab Followed by Surgical Resection and Adjuvant Chemoradiation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gastric Cancer
Stomach Cancer
Keywords: stomach cancer
biologics
antibody
chemotherapy
chemoradiation
adjuvant therapy
neoadjuvant therapy
epidermal growth factor receptor
combination therapy
Lead sponsor: NYU Langone Health
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
name: Eli Lilly and Company
First posted: 2009-03-06
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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).

Primary outcomes:
measure: Clinical Response Rate of an Induction Regimen Consisting of Irinotecan, Cisplatin and Cetuximab
timeFrame: 4 months from the beginning of the induction regimen
Secondary outcomes:
measure: Rate of Clearance of Nodal Involvement Among Patients Who Have Received the Induction Therapy
timeFrame: 4 months from the beginning of the induction treatment
measure: Rate of Potentially Curative Surgery
timeFrame: 4 months from the beginning of the induction treatment
measure: Rate of "Down-staging" From Pre-operative Clinical Staging
timeFrame: 4 months from the beginning of the induction treatment
measure: Safety of the Induction Regimen
timeFrame: 4 months from the beginning of the induction
measure: Median Overall Survival (Induction Treatment and Curative Surgery)
timeFrame: up to 5 years
measure: Median Overall Survival (Adjuvant Therpary)
timeFrame: up to 5 years
Other outcomes:
Locations:
city: New York
country: United States
facility: NYU Cancer Center
state: New York
Study officials:
affiliation: NYU Langone Health
name: Theresa Ryan, MD
role: PRINCIPAL_INVESTIGATOR
References: