Esophageal Neoplasms, Stomach Neoplasms
Conditions
Keywords
Metastatic, Gastroesophageal, Docetaxel, Cisplatin, Fluorouracil, Bevacizumab, Metastatic Gastroesophageal Adenocarcinoma, 06-096
Brief summary
This study is being done to find out what effects a drug named/called bevacizumab has on patients and patients' tumors when given together with standard chemotherapy drugs. Making new blood vessels seems to be important for many tumors to grow. Bevacizumab is a new type of treatment for cancer that blocks the growth of new tumor blood vessels. In this study, the researchers will combine bevacizumab with chemotherapy drugs that are standard for the patient's disease and include cisplatin, docetaxel, fluorouracil, and leucovorin. The way the original combination of cisplatin, docetaxel, and fluorouracil was given caused many side effects including gastrointestinal symptoms, weakness, and a drop in the blood count of infection fighting cells. For this study, the researchers have modified this combination to give lower doses of the medicines more often, to reduce side effects from the chemotherapy. Patients will receive bevacizumab with this modified combination of docetaxel, cisplatin, and fluorouracil. This study is called a phase II study. In this study, everyone will have similar tumors and receive the same treatment.
Interventions
DRUGDocetaxel, Cisplatin, Fluorouracil, Bevacizumab, Leucovorin
Bevacizumab 10mg/kg day 1 IV over 30 minutes Docetaxel 40mg/m2 day 1 IV over 1 hour Leucovorin 400mg/m2 day 1 IV over 30 minutes Fluorouracil 400mg/m2 IVP day 1 Fluorouracil 1000mg/m2 IVCI x 48 hours Cisplatin 40mg/m2 day 3 IV over 30 minutes
Sponsors
Sanofi
Genentech, Inc.
Memorial Sloan Kettering Cancer Center
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 histologically or cytologically confirmed metastatic or unresectable gastric or esophageal adenocarcinoma, including GEJ adenocarcinoma which will be classified according to Siewert's classification type I, II, or III. * Histological documentation of local recurrence or metastasis is strongly encouraged, unless the risk of such a procedure outweighs the potential benefit of confirming the metastatic disease. * If no histologic confirmation, then the metastases or recurrence will require documentation by a 2nd radiographic procedure (i.e. positron emission tomography \[PET\] scan or magnetic resonance imaging \[MRI\] in addition to the computed tomography \[CT\] scan). If the imaging procedure does not confirm recurrent or metastatic disease, biopsy confirmation will be required. * Patients must have disease that can be evaluated radiographically. This may be measurable disease or non-measurable disease. Measurable disease is defined as that which can be measured in at least one dimension as \> or = 20 mm with conventional techniques, or \> or = 10 mm by high resolution imaging. Disease that is identified on radiology studies, but does not meet the criteria for measurable disease, is considered non-measurable - see section 12.1.1 of protocol for further details. * No prior chemotherapy for metastatic or unresectable disease. Patients may have received prior adjuvant therapy (chemotherapy and/or chemoradiation) if more than 6 months have elapsed between the end of adjuvant therapy and registration. Patients may not have received prior docetaxel or cisplatin, or bevacizumab or any other novel biologic anti-angiogenic agent. * Age 18 years or older. * Karnofsky performance status \> or = 70% (ECOG performance status 0-1). * Peripheral neuropathy \< or = grade 1 * Hematologic (minimal values): * White blood cell count \> or = 3000/mm3 * Absolute neutrophil count \> or = 1500 cells/mm3 * Hemoglobin \> or = 9.0 g/dl * Platelet count \> or = 100,000/mm3 * Hepatic (minimal values): * Total bilirubin \< or = to upper limit of normal (ULN) * AST and ALT and alkaline phosphatase must be within the eligible range. In determining eligibility, the more abnormal of the two values (AST or ALT) should be used. AST and ALT and alkaline phosphatase should be no more than 1-1.5 times the upper limit of normal. * Kidney function (minimal values): * Serum creatinine \< or = 1.5 mg/dl * Urinalysis \< 2+ proteinuria; urine protein (mg/dl)/urine creatinine (mg/dl) ratio (Up/c) \< 1.0 * The patient has a PT (INR) \< or = 1.5 and a PTT \< or = 3 seconds above the upper limits of normal if the patient is not on anticoagulation therapy. If a patient is on full-dose anticoagulants, the following criteria should be met for enrollment: 1. The patient must have an in-range INR (usually between 2 and 3) on a stable dose of warfarin or on stable dose of LMW heparin. 2. The patient must not have active bleeding or pathological conditions that carry high risk of bleeding (e.g. tumor involving major vessels, known varices). * Women of childbearing potential must have a negative pregnancy test. Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter. * Ability to understand informed consent and signing of written informed consent document prior to initiation of protocol therapy.
Exclusion criteria
* Patients who have received previous chemotherapy for the treatment of metastatic or unresectable gastric, GEJ, or esophageal adenocarcinoma are ineligible. Patients who have received previous pre- or post-operative chemotherapy or chemoradiation are ineligible if therapy was completed less than 6 months prior to study registration. Patients must have recovered from adverse events from any previous therapy. * Patients who have received previous bevacizumab, docetaxel, or cisplatin. * Patients with a history of another neoplastic disease within the past three years, excluding basal cell carcinoma of the skin, cervical carcinoma in situ, or nonmetastatic prostate cancer. * Patients with brain or central nervous system metastases, including leptomeningeal disease. * Minor surgical procedure such as fine needle aspiration, core biopsy, laparoscopy, or mediport placement within 7 days prior to initiating treatment. * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day 0 * Anticipation of need for major surgical procedure during the course of the study. * Pregnant (positive pregnancy test) or breast feeding. * Urine protein:creatinine (Up/c) ratio \> or = 1.0 at screening * History of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess within 6 months prior to the initiation of treatment. * Serious, non-healing wound, ulcer, or bone fracture. * Blood pressure \> 150/100 mmHg * Significant cardiac disease defined as: * Unstable angina * New York Heart Association (NYHA) grade II or greater * Congestive heart failure * History of myocardial infarction within 6 months * Evidence of bleeding diathesis or coagulopathy. * History of a stroke or cerebrovascular accident (CVA) within 6 months. * Clinically significant peripheral vascular disease. * Clinically significant hearing loss or ringing in the ears. * Patients with a history of severe hypersensitivity reaction to Taxotere® or other drugs formulated with polysorbate 80. * Inability to comply with study and/or follow-up procedures. * Patients with any other medical condition or reason, in the investigator's opinion, that makes the patient unstable to participate in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 6 Month Progression Free Survival | 6 months | as measured from the start of the treatment to the date of either documentation of disease progression or death. As we have previously, we will define progression of disease as per RECIST criteria. As per RECIST criteria, any evidence of progression in non-measurable lesions, measurable lesions, or the development of new lesions, would qualify as disease progression .RECIST criteria as defined by CTEP (http://ctep.info.nih.gov/Policies). |
| 1-year Survival | 1 year | — |
Secondary
| Measure | Time frame |
|---|---|
| Patients With Measurable Disease the Confirmed Response Rate | up to 2 years |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Docetaxel, Cisplatin, Fluorouracil, Bevacizumab, Leucovorin Bevacizumab 10mg/kg day 1 IV over 30 minutes Docetaxel 40mg/m2 day 1 IV over 1 hour Leucovorin 400mg/m2 day 1 IV over 30 minutes Fluorouracil 400mg/m2 IVP day 1 Fluorouracil 1000mg/m2 IVCI x 48 hours Cisplatin 40mg/m2 day 3 IV over 30 minutes | 48 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Not treated | 3 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Docetaxel, Cisplatin, Fluorouracil, Bevacizumab, Leucovorin |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 8 Participants |
| Age, Categorical Between 18 and 65 years | 40 Participants |
| Region of Enrollment United States | 48 participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 44 / 48 |
| serious Total, serious adverse events | 27 / 48 |
Outcome results
Primary
1-year Survival
Time frame: 1 year
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Docetaxel, Cisplatin, Fluorouracil, Bevacizumab, Leucovorin | 1-year Survival | Progression Free Survival | 12 months |
| Docetaxel, Cisplatin, Fluorouracil, Bevacizumab, Leucovorin | 1-year Survival | Overall Survival | 16.8 months |
Primary
6 Month Progression Free Survival
as measured from the start of the treatment to the date of either documentation of disease progression or death. As we have previously, we will define progression of disease as per RECIST criteria. As per RECIST criteria, any evidence of progression in non-measurable lesions, measurable lesions, or the development of new lesions, would qualify as disease progression .RECIST criteria as defined by CTEP (http://ctep.info.nih.gov/Policies).
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Docetaxel, Cisplatin, Fluorouracil, Bevacizumab, Leucovorin | 6 Month Progression Free Survival | 79 percentage of participants |
Secondary
Patients With Measurable Disease the Confirmed Response Rate
Time frame: up to 2 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Docetaxel, Cisplatin, Fluorouracil, Bevacizumab, Leucovorin | Patients With Measurable Disease the Confirmed Response Rate | Confirmed Response Rate | 67 percentage of participants |
| Docetaxel, Cisplatin, Fluorouracil, Bevacizumab, Leucovorin | Patients With Measurable Disease the Confirmed Response Rate | Response Rate (proximal/GEJ tumors) | 85 percentage of participants |