Gastric (Stomach) Cancer, Gastrointestinal Stromal Tumor (GIST), Neoplasm of Cardioesophageal Junction, Stomach Cancer
Conditions
Brief summary
To investigate bevacizumab in combination with carboplatin and capecitabine for patients with unresectable or metastatic GEJ or gastric cancers. We hope that by adding bevacizumab to standard chemotherapy for this patient population we will improve Progression Free Survival by 90% over historical controls.
Detailed description
Primary Objectives: To investigate if the addition of Bevacizumab to standard chemotherapy for metastatic or unresectable GEJ and gastric adenocarcinoma will improve PFS by 90% over historical controls. Secondary Objectives: * Assess toxicities using CTCAE v3.0 * Evaluate overall survival (OS) using Kaplan-Meier analysis * Evaluate objective response rate (RR) by RECIST criteria * Explore biomarkers of tumor response: CEA, CA 19.9, and serum VEGF * Bank serum and tissue for future correlative studies * Evaluate CT Perfusion to predict early therapeutic response to combination chemotherapy and anti-angiogenic therapy (OPTIONAL).
Interventions
DRUGbevacizumab
Intravenous 15 mg/kg
DRUGcarboplatin
AUC 6, Intravenously Day 1 every 21 days
DRUGcapecitabine
850mg/m2, Orally twice daily days 1-14 every 21 days.
Sponsors
Genentech, Inc.
Stanford University
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
Subjects must be treated at Stanford University Medical Center for the entire length of study participation. 1. Patients with histologically or cytologically confirmed adenocarcinoma of the GEJ or stomach. 2. Patients must be deemed unresectable due to involvement of critical vasculature or adjacent organ invasion. If unresectable, patients must show evidence of disease progression prior to enrollment. 3. Patients with prior surgical resection who develop radiological or clinical evidence of metastatic cancer do not require separate histological or cytological confirmation of metastatic disease unless an interval of \> 5 years has elapsed between the primary surgery and the development of metastatic disease. Clinicians should consider biopsy of lesions to establish diagnosis of metastatic disease if there is substantial clinical ambiguity regarding the nature or source of apparent metastases. 4. Prior carboplatin as neoadjuvant or adjuvant therapy will be allowed if \>= 6 months from the time of study entry. 5. If patients use aspirin (\>325mg/day) or NSAIDS at the time of enrollment, they must have a 10 day washout period prior to beginning protocol treatment. 6. Low molecular weight heparin (or its equivalent, excluding warfarin) will be allowed for treatment of venous thromboembolic events if patients have no evidence of bleeding on full-dose anticoagulation. 7. Patients must have a primary or metastatic lesion measurable in at least one dimension by Modified RECIST criteria (see Section 11.2.3) within 4 weeks prior to entry of study 8. Patients must have ECOG performance status of 0-1 9. Patients must be \>= 18 years of age 10. Laboratory values \<= 2 weeks prior to randomization: * Absolute Neutrophil Count (ANC) \>= 1.5 x 109/L (\>= 1500/mm3) * Platelets (PLT) \>= 100 x 109/L (\>= 100,000/mm3) * Hemoglobin (Hgb) \>= 9 g/dL * Serum creatinine \<= 1.5 x ULN * Serum bilirubin \<= 1.5 x ULN (\<= 3.0 x ULN if liver metastases present) * Aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT) \<= 3.0 x ULN (\<= 5.0 x ULN if liver metastases present). Note: ERCP or percutaneous stenting may be used to normalize the liver function tests. 11. Life expectancy \>= 12 weeks 12. Inclusion and
Exclusion criteria
for DCE-MRI and DWI imaging will be determined by CT scan as part of routine post-chemotherapy imaging. Subjects will be eligible if one liver metastasis is greater than 1 cm in size. Participation in the DCE-MRI and DWI correlate is not required for eligibility. 13. Ability to give written informed consent according to local guidelines
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | 12 months | Tumor progression was assessed according to the Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1), presented below. * Complete Response (CR) = Disappearance of all target lesions * Partial Response (PR) = ≥ 30% decrease in the sum of the longest diameter of target lesions * Objective Response (OR) = CR + PR * Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s) * Stable disease (SD) = Small changes that do not meet any of the above criteria. Progression-Free Survival is assessed as the number of evaluable participants who were alive without disease progression at 1 year. Participants without out assessment at 12 months will not be included. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events ≥ Grade 3 and Related to Bevacizumab | 12 months | Toxicity was assessed as the number of adverse events ≥ Grade 3 and also possibly, probably, or definitely related to bevacizumab. The outcome is reported as the total number of applicable events, and as the number of events that were a hematologic toxicity; a non-hematologic toxicity; which are numbers without dispersion. |
| Overall Survival (OS) | 7.5 years | Overall survival (OS) will be assessed from time from the date of enrollment to the date of death due to any cause or the last date the patient was known to be alive (censored observation) at the date of data cutoff for the final analysis. The outcome is presented as the median survival in days with standard deviation. |
| Objective (Overall) Therapeutic Response | 12 months | Tumor response was assessed per the Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1) for target lesions, and assessed by physical measurement; magnetic resonance imaging (MRI); computed tomography (CT), positron emission tomography (PET)-CT; and/or X-rays/radiologic scan. Response was determined based on the criteria below. * Complete Response (CR) = Disappearance of all target lesions * Partial Response (PR) = ≥ 30% decrease in the sum of the longest diameter of target lesions * Objective Response (OR) = CR + PR * Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s) * Stable disease (SD) = Small changes that do not meet any of the above criteria The outcome is provided as the number of participants who achieved each of the defined responses, with objective (overall) response defined as the sum of CR and PR. The outcome is reported as values without dispersion. |
| CEA and CA 19.9 Tumor Response Biomarkers | 9 weeks | The detected blood levels for tumor biomarkers CEA and CA 19.9 were to be correlated to the results for progression-fee survival (PFS), with the outcome presented as the median with standard deviation. |
| Vascular Endothelial Growth Factor Tumor Response Biomarker | 9 weeks | The detected blood levels for tumor biomarker vascular endothelial growth factor (VEGF) were to be correlated to the results for progression-fee survival (PFS), with the outcome presented as the median with standard deviation. |
Countries
United States
Participant flow
Recruitment details
Indicated participant number is accurate for the number of subjects who started study treatment and completed treatment.
Participants by arm
| Arm | Count |
|---|---|
| Bevacizumab+ Carboplatin +Capecitabine Participants receive bevacizumab 15 mg/kg intravenously followed by carboplatin AUC 6 intravenously on Day 1 of a 21-day cycle, concurrently with capecitabine 850 mg/m2 twice-daily by mouth on Cycle Days 1-to-14, followed by a 1-week break. | 35 |
| Total | 35 |
Baseline characteristics
| Characteristic | Bevacizumab+ Carboplatin +Capecitabine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 25 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Age, Continuous | 56.7 years STANDARD_DEVIATION 14.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants |
| Race (NIH/OMB) Black or African American | 0 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 | 3 Participants |
| Race (NIH/OMB) White | 27 Participants |
| Region of Enrollment United States | 35 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 31 / 35 |
| other Total, other adverse events | 35 / 35 |
| serious Total, serious adverse events | 35 / 35 |
Outcome results
Primary
Progression-Free Survival (PFS)
Tumor progression was assessed according to the Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1), presented below. * Complete Response (CR) = Disappearance of all target lesions * Partial Response (PR) = ≥ 30% decrease in the sum of the longest diameter of target lesions * Objective Response (OR) = CR + PR * Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s) * Stable disease (SD) = Small changes that do not meet any of the above criteria. Progression-Free Survival is assessed as the number of evaluable participants who were alive without disease progression at 1 year. Participants without out assessment at 12 months will not be included.
Time frame: 12 months
Population: Those participants who did not receive follow-up at 12 months were considered lost-to-follow-up and not evaluable for progression, and were censored from the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Bevacizumab+ Carboplatin +Capecitabine | Progression-Free Survival (PFS) | 9 Participants |
Secondary
Adverse Events ≥ Grade 3 and Related to Bevacizumab
Toxicity was assessed as the number of adverse events ≥ Grade 3 and also possibly, probably, or definitely related to bevacizumab. The outcome is reported as the total number of applicable events, and as the number of events that were a hematologic toxicity; a non-hematologic toxicity; which are numbers without dispersion.
Time frame: 12 months
Population: All participants were included in this analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab+ Carboplatin +Capecitabine | Adverse Events ≥ Grade 3 and Related to Bevacizumab | Total Toxicity Events | 18 Adverse events |
| Bevacizumab+ Carboplatin +Capecitabine | Adverse Events ≥ Grade 3 and Related to Bevacizumab | Total Hematologic Toxicities | 3 Adverse events |
| Bevacizumab+ Carboplatin +Capecitabine | Adverse Events ≥ Grade 3 and Related to Bevacizumab | Total Non-hematologic Toxicities | 15 Adverse events |
Secondary
CEA and CA 19.9 Tumor Response Biomarkers
The detected blood levels for tumor biomarkers CEA and CA 19.9 were to be correlated to the results for progression-fee survival (PFS), with the outcome presented as the median with standard deviation.
Time frame: 9 weeks
Population: Based on the objective results, it was determined that the any results from tumor biomarker analyses would be of little value, and the measurement for tumor biomarkers in the collected samples were not conducted. Accordingly, there is no data to be analyzed.
Secondary
Objective (Overall) Therapeutic Response
Tumor response was assessed per the Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1) for target lesions, and assessed by physical measurement; magnetic resonance imaging (MRI); computed tomography (CT), positron emission tomography (PET)-CT; and/or X-rays/radiologic scan. Response was determined based on the criteria below. * Complete Response (CR) = Disappearance of all target lesions * Partial Response (PR) = ≥ 30% decrease in the sum of the longest diameter of target lesions * Objective Response (OR) = CR + PR * Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s) * Stable disease (SD) = Small changes that do not meet any of the above criteria The outcome is provided as the number of participants who achieved each of the defined responses, with objective (overall) response defined as the sum of CR and PR. The outcome is reported as values without dispersion.
Time frame: 12 months
Population: Data for clinical response was not available for all participants. Response data are only reported for participants for whom response is known.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Bevacizumab+ Carboplatin +Capecitabine | Objective (Overall) Therapeutic Response | Partial Response | 18 Participants |
| Bevacizumab+ Carboplatin +Capecitabine | Objective (Overall) Therapeutic Response | Complete Response (CR) | 0 Participants |
| Bevacizumab+ Carboplatin +Capecitabine | Objective (Overall) Therapeutic Response | Objective Response (OR) = CR + PR | 18 Participants |
| Bevacizumab+ Carboplatin +Capecitabine | Objective (Overall) Therapeutic Response | Stable Disease | 6 Participants |
| Bevacizumab+ Carboplatin +Capecitabine | Objective (Overall) Therapeutic Response | Progressive Disease | 5 Participants |
Secondary
Overall Survival (OS)
Overall survival (OS) will be assessed from time from the date of enrollment to the date of death due to any cause or the last date the patient was known to be alive (censored observation) at the date of data cutoff for the final analysis. The outcome is presented as the median survival in days with standard deviation.
Time frame: 7.5 years
Population: Data were available for all participants. Participants remaining alive were censored at last date assessed.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Bevacizumab+ Carboplatin +Capecitabine | Overall Survival (OS) | 458 Days | Standard Deviation 738 |
Secondary
Vascular Endothelial Growth Factor Tumor Response Biomarker
The detected blood levels for tumor biomarker vascular endothelial growth factor (VEGF) were to be correlated to the results for progression-fee survival (PFS), with the outcome presented as the median with standard deviation.
Time frame: 9 weeks
Population: Studies published during the conduct of this study demonstrated that this assessment was not useful, and the samples were not collected. Accordingly, there is no data to be analyzed.