Gastric Cancer, Stomach Cancer
Conditions
Keywords
stomach cancer, biologics, antibody, chemotherapy, chemoradiation, adjuvant therapy, neoadjuvant therapy, epidermal growth factor receptor, combination therapy
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.
Interventions
DRUGCetuximab
DRUGIrinotecan
DRUGCisplatin
PROCEDURESurgery
DRUG5-FU
RADIATIONRadiation
Sponsors
Bristol-Myers Squibb
Eli Lilly and Company
NYU Langone Health
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Recruitment details
From October 2005 to November 2010, 30 patients were enrolled to the study from New York University Langone Medical Center and its affiliated hospitals.
Participants by arm
| Arm | Count |
|---|---|
| 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 (3-4 weeks after induction treatment).
3. Chemoradiation treatment (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 | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| ChemoRT | Adverse Event | 2 |
| ChemoRT | Withdrawal by Subject | 1 |
| Induction Regimen | Adverse Event | 1 |
| Induction Regimen | disease-related complications | 1 |
| Induction Regimen | Withdrawal by Subject | 1 |
| Surgery (Curative) | disease progression | 6 |
Baseline characteristics
| Characteristic | Induction/ Surgery/ chemoRT |
|---|---|
| Age, Customized 25-34 years | 1 participants |
| Age, Customized 35-44 years | 1 participants |
| Age, Customized 45-53 years | 8 participants |
| Age, Customized 54-63 years | 12 participants |
| Age, Customized 64-73 years | 3 participants |
| Age, Customized 74-83 years | 5 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 13 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 11 Participants |
| Region of Enrollment United States | 30 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 30 / 30 |
| serious Total, serious adverse events | 15 / 30 |
Outcome results
Primary
Clinical Response Rate of an Induction Regimen Consisting of Irinotecan, Cisplatin and Cetuximab
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.
Time frame: 4 months from the beginning of the induction regimen
Population: Evaluable patients (known pre-treatment clinical and post-treatment pathologic stages)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction/ Surgery/ chemoRT | Clinical Response Rate of an Induction Regimen Consisting of Irinotecan, Cisplatin and Cetuximab | 40 percentage of paticipants |
Secondary
Median Overall Survival (Adjuvant Therpary)
This is the length of time from the start of treatment that half of the patients are still alive.
Time frame: up to 5 years
Population: Patients who received at least one cycle of adjuvant therapy
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Induction/ Surgery/ chemoRT | Median Overall Survival (Adjuvant Therpary) | 39.5 months |
Secondary
Median Overall Survival (Induction Treatment and Curative Surgery)
This is the length of time from the start of treatment that half of the patients are still alive.
Time frame: up to 5 years
Population: Patients who completed induction treatment and underwent curative surgery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Induction/ Surgery/ chemoRT | Median Overall Survival (Induction Treatment and Curative Surgery) | 35.3 months |
Secondary
Rate of Clearance of Nodal Involvement Among Patients Who Have Received the Induction Therapy
This is defined as the percentage of patients whose nodal involvement of cancer has been cleared based on surgery results.
Time frame: 4 months from the beginning of the induction treatment
Population: Evaluable patients (known pre-treatment clinical and post-treatment pathologic stages)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction/ Surgery/ chemoRT | Rate of Clearance of Nodal Involvement Among Patients Who Have Received the Induction Therapy | 0 percentage of participants |
Secondary
Rate of Down-staging From Pre-operative Clinical Staging
This is defined as the percentage of patients who had a reduction from T3/T4 disease.
Time frame: 4 months from the beginning of the induction treatment
Population: Evaluable patients (known pre-treatment clinical and post-treatment pathologic stages)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction/ Surgery/ chemoRT | Rate of Down-staging From Pre-operative Clinical Staging | 53 percentage of participants |
Secondary
Rate of Potentially Curative Surgery
This is defined as the percentage of patients who underwent curative surgery (surgery to remove all cancerous tissue).
Time frame: 4 months from the beginning of the induction treatment
Population: patients who underwent surgery
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction/ Surgery/ chemoRT | Rate of Potentially Curative Surgery | 78 percentage of participants |
Secondary
Safety of the Induction Regimen
This describes the number of patients who experienced grade 3 and higher adverse events related to the regimen.
Time frame: 4 months from the beginning of the induction
Population: Patients who had at least a dose of treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Induction/ Surgery/ chemoRT | Safety of the Induction Regimen | Dehydration | 1 participants |
| Induction/ Surgery/ chemoRT | Safety of the Induction Regimen | Neutrophils/granulocytes | 13 participants |
| Induction/ Surgery/ chemoRT | Safety of the Induction Regimen | Diarrhea | 4 participants |
| Induction/ Surgery/ chemoRT | Safety of the Induction Regimen | Fatigue | 3 participants |
| Induction/ Surgery/ chemoRT | Safety of the Induction Regimen | Rash | 3 participants |
| Induction/ Surgery/ chemoRT | Safety of the Induction Regimen | Leukocytes | 2 participants |
| Induction/ Surgery/ chemoRT | Safety of the Induction Regimen | Hypomagnesmia | 2 participants |
| Induction/ Surgery/ chemoRT | Safety of the Induction Regimen | Hypotension | 2 participants |
| Induction/ Surgery/ chemoRT | Safety of the Induction Regimen | Lymphopenia | 1 participants |
| Induction/ Surgery/ chemoRT | Safety of the Induction Regimen | Vomiting | 1 participants |
| Induction/ Surgery/ chemoRT | Safety of the Induction Regimen | Hypophosphatemia | 1 participants |
| Induction/ Surgery/ chemoRT | Safety of the Induction Regimen | Hypokelemia | 1 participants |
| Induction/ Surgery/ chemoRT | Safety of the Induction Regimen | Stomatitis/Pharyngitis | 1 participants |
| Induction/ Surgery/ chemoRT | Safety of the Induction Regimen | Febrile neutropenia | 1 participants |
| Induction/ Surgery/ chemoRT | Safety of the Induction Regimen | Hemoglobin | 1 participants |
| Induction/ Surgery/ chemoRT | Safety of the Induction Regimen | Carpopedal syndrome | 1 participants |