Esophageal Cancer, Gastric Cancer
Conditions
Keywords
Gastroesophageal Junction Cancer
Brief summary
This study is for people with advanced gastric or gastroesophageal cancer. This study is being done to find out how long it takes tumors to grow after patients take the drugs capecitabine, oxaliplatin and cetuximab. Capecitabine (also called Xeloda) is a drug that has been approved by the Food and Drug Administration (FDA). Capecitabine has been approved for treatment of cancer of the colon and rectum. Oxaliplatin is another drug approved by the FDA. Oxaliplatin is also approved for treatment of cancer of the colon and rectum. Cetuximab is also a drug approved by the FDA for the treatment of cancer of the colon and rectum, as well as cancer of the head and neck. Capecitabine, oxaliplatin and cetuximab are not approved for gastric or gastroesophageal cancer. They are considered experimental drugs for this study. The purpose of this study is to see how long it takes patients' tumors to progress when they are taking oxaliplatin and capecitabine. Another purpose is to see how many tumors respond to this drug combination. The investigators also want to see how long people live when taking these drugs. The side effects of this drug combination will also be evaluated. This study will also measure the levels of certain genes (the cell's blueprint) in tumors. These genes affect how peoples' bodies react to the cancer drugs. Genes will also be measured in the blood. The investigators want to see how these genes can predict response to these study drugs.
Interventions
cetuximab 400 mg/m2, followed by weekly cetuximab 250 mg/m2 with oxaliplatin 130 mg/m2 on day 1 (every 3 weeks) with capecitabine 850 mg/m2 bid, daily on days 1-14, every 3 weeks.
Sponsors
University of Southern California
Sanofi
Roche Global Development
Bristol-Myers Squibb
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with histologically or cytologically confirmed advanced or metastatic gastric or gastroesophageal cancer. Histology must be consistent with adenocarcinoma. * No previous chemotherapy for metastatic or unresectable disease. Prior adjuvant therapy is allowed, as long as it was completed within six months of study initiation. * Ability to understand and willingness to sign a written informed consent prior to study-specific screening procedures, with the understanding that the patient has the right to withdraw from the study at any time, without prejudice. * SWOG performance status of less than or equal to 2. * At least one measurable lesion, according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, which has not been irradiated (i.e. newly arising lesions in previously irradiated areas are accepted). Ascites, pleural effusion, and bone metastases are not considered measurable. Minimum indicator lesion size: \> 10 mm measured by spiral computed tomography (CT) or \> 20 mm measured by conventional techniques. * Have a negative serum or urine pregnancy test within 7 days prior to initiation of chemotherapy (female patients of childbearing potential). * Availability of tumor biopsy (paraffin embedded or fresh frozen) at the time of diagnosis and/or prior to study entry is required. * Patients must agree to use an effective form of birth control while on study and to continue this contraceptive method for 30 days from the date of the last study drug administration.
Exclusion criteria
* Pregnant or lactating women. * Life expectancy of \< 3 months. * Serious, uncontrolled, concurrent infection(s) or illness(es). * Any prior oxaliplatin treatment. * Prior unanticipated severe reaction to fluoropyrimidine therapy, known hypersensitivity to 5-fluorouracil or known DPD deficiency. * Prior unanticipated severe reaction or hypersensitivity to platinum based compounds. * Completion of previous chemotherapy regimen \< four weeks prior to the start of study treatment (within six weeks of study treatment for mitomycin C and nitroureas), or with related toxicities unresolved prior to the start of study treatment. * Treatment for other carcinomas within the last five years, except for cured non-melanoma skin cancer and treated in-situ cervical cancer. * Participation in any investigational drug study within 4 weeks preceding the start of study treatment. * Clinically significant cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 12 months. * History of clinically significant interstitial lung disease and/or pulmonary fibrosis. * History of persistent neurosensory disorder including but not limited to peripheral neuropathy * Evidence of central nervous system (CNS) metastases (unless CNS metastases have been stable for \> 3 months) or history of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance of oral drug intake. Other serious uncontrolled medical conditions that the investigator feels might compromise study participation. * Major surgery within 4 weeks of the start of study treatment, without complete recovery. * Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome. * Any of the following laboratory values: * Abnormal hematologic values (neutrophils \< 1.5 x 10\^9/L, platelet count \< 100 x 109/L) * Impaired renal function (estimated creatinine clearance \< 30 ml/min as calculated with Cockroft-Gault equation and serum creatinine \> 1.5 x upper normal limit). * Serum bilirubin \> 1.5 x upper normal limit. * ALT, AST \> 2.5 x upper normal limit (or \> 5 x upper normal limit in the case of liver metastases). * Alkaline phosphatase \> 2.5 x upper normal limit (or \> 5 x upper normal limit in the case of liver metastases or \> 10 x upper normal limit in the case of bone disease). * Unwillingness to participate or inability to comply with the protocol for the duration of the study. * Known, existing uncontrolled coagulopathy * Prior therapy which specifically and directly targets the EGFR pathway. * Prior severe infusion reaction to a monoclonal antibody
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Progression-Free Survival (PFS) at Month 4 | every 2 cycles (6 weeks), up to 4 months. | Progression-free survival will be measured from the start of treatment until the time the patient is first recorded as having disease progression, or death due to any cause. If a patient has not progressed or died, progression-free survival is censored at the time of last visit for tumor measurement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression | every 2 cycles (6 weeks), through study completion up to 2 years, 7 months | The overall time to progression in patients with advanced gastric or gastroesophageal junction cancer treated with a combination of capecitabine and oxaliplatin. This differs from 4 months PFS rate outcome data, which assesses the progression-free survival at 4 months. |
| Number of Participants Who Experienced Toxicities During the Study Drug Regimen | About 2 years, 7 months | — |
| Overall Response Rate | Every 2 cycles (6 weeks), through study completion, up to 2 years, 7 months | To determine overall response rate in patients with advanced gastric or gastroesophageal junction cancer treated with a combination of capecitabine and oxaliplatin |
| Overall Survival | Every 2 cycles (6 weeks), through study completion, up to 2 years, 7 months | To determine overall survival in patients with advanced gastric or gastroesophageal junction cancer treated with a combination of capecitabine and oxaliplatin |
| Progression-free Survival (PFS) | Every 2 cycles (6 weeks), through study completion, up to 2 years, 7 months | Progression-free survival (PFS), Median (95%CI), months |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORSyma Iqbal, M.D.
U.S.C./Norris Comprehensive Cancer Center
Participant flow
Recruitment details
Recruitment for this study opened in December 2004 and closed in January 2012. All subjects were seen and treated in the medical clinics at the University of Southern California, Los Angeles General Medical Center, and Los Angeles Clinic and Research Institute.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 56 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 33 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Karnofsky performance status % 100% | 1 Participants |
| Karnofsky performance status % 70% | 3 Participants |
| Karnofsky performance status % 80% | 28 Participants |
| Karnofsky performance status % 90% | 28 Participants |
| Karnofsky performance status % Missing | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 13 Participants |
| Race (NIH/OMB) Black or African American | 2 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 | 32 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Region of Enrollment United States | 61 participants |
| Sex: Female, Male Female | 19 Participants |
| Sex: Female, Male Male | 42 Participants |
| Site of primary tumor GE Junction | 2 Participants |
| Site of primary tumor Stomach | 59 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 75 |
| other Total, other adverse events | 74 / 75 |
| serious Total, serious adverse events | 54 / 75 |
Outcome results
None listed