Urologic Neoplasm
Conditions
Keywords
urothelial, urologic, neoplasm, advanced, metastatic
Brief summary
The purpose of this research study is to determine whether the investigational drug cetuximab, (Erbitux) alone or with paclitaxel (Taxol) can stabilize the growth of urothelial cancer.
Detailed description
This research study is being done to find out if cetuximab, alone or with paclitaxel will slow the growth of urothelial cancers. Cetuximab is an antibody that blocks a protein called epidermal growth factor receptor (EGFR). EGFR sits on the outside of tumor cells and controls tumor cell growth. This agent has been looked at alone and with other chemotherapy drugs including paclitaxel. It has been found to be safe and can shrink other types of cancer. This research study is also being done to find out if cetuximab, alone or with paclitaxel shrinks urothelial tumors. If it extends the time the tumors shrink. If it helps people live longer. The purpose of this research study is to find out what effects (good and bad) these treatments have on you and your cancer. We do not know if you will benefit from this research study. It is possible that your condition will get better, but it is also possible that there will be no effect on your condition or that your condition will get worse. We can use what we learn from this research study to help other people with the same disease.
Interventions
DRUGCetuximab
Cetuximab 250mg/m2 IV weekly for each 28 day cycle.
DRUGPaclitaxel
Paclitaxel 80mg/m2 IV weekly for each 28 day cycle.
Sponsors
Bristol-Myers Squibb
Fox Chase Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed carcinoma of the urothelium (bladder,renal pelvis, ureter) * Measurable disease by RECIST * Patients who received only one prior systemic non-taxane regimen for urothelial cancer. May have received this in the adjuvant or neoadjuvant setting or for advanced disease. * Signed IRB approved consent * Must have tissue available for EGFR assessment and additional correlative studies * ECOG PS 0-2 * 18 years of age or older * Not of child bearing potential or negative pregnancy test within 7 days of treatment * ANC greater than or equal to 1,500/ul * Platelets greater than or equal to 100,00/ul * Creatinine less than or equal to 2x institutional ULN or create. clearance greater than or equal to 30, bilirubin less than or equal to 1.5x ULN, AST&ALT less than or equal to 5x ULN
Exclusion criteria
* Received more than one prior regimen for advanced disease * Prior radiation to more than 30% of marrow containing skeleton * Prior therapy that specifically and directly targets the EGFR pathway * Prior severe infusion reaction to a monoclonal antibody, pre-existing neuropathy greater than or equal to grade 2 * Prior reaction to Cremophor EL * Known acute hepatitis B or C or known HIV * Active or uncontrolled infection * Significant history of uncontrolled cardiac disease * Any concurrent chemotherapy not indicated in this study; or * Any other investigational agents
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression Free Survival | Measures by CT scans following each 2 cycles of treatment and about every 8 weeks after off treatment for disease progression. Follow up for survival until time of death. |
Secondary
| Measure | Time frame |
|---|---|
| Response Rate, Duration of Response, Time to Progression Will be Assessed With Radiographic Imaging | Measured by CT scans after every 2 cycles of treatment (about every 8 weeks) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm A - Cetuximab Treatment Arm Cetuximab 250mg/m2 IV weekly during each 28 day cycle. Arm A closed to accrual June 11, 2009 for lack of efficacy
Cetuximab: Cetuximab 250mg/m2 IV weekly for each 28 day cycle. | 11 |
| Arm B Paclitaxel and Cetuximab Combination Treatment Arm Paclitaxel 80 mg/m2 IV weekly for every 28 day cycle. Cetuximab 250mg/m2 IV weekly for every 28 day cycle.
Cetuximab: Cetuximab 250mg/m2 IV weekly for each 28 day cycle.
Paclitaxel: Paclitaxel 80mg/m2 IV weekly for each 28 day cycle. | 28 |
| Total | 39 |
Baseline characteristics
| Characteristic | Total | Arm B Paclitaxel and Cetuximab Combination Treatment Arm | Arm A - Cetuximab Treatment Arm |
|---|---|---|---|
| Age, Continuous | 69 years | 69 years | 70 years |
| Performance Status 0-1 | 36 participants | 25 participants | 11 participants |
| Performance Status 2 | 3 participants | 3 participants | 0 participants |
| Previous Chemotherapy, No. of Patients Gemcitabine and Platinum | 37 Participants | 26 Participants | 11 Participants |
| Previous Chemotherapy, No. of Patients MVAC | 2 Participants | 2 Participants | 0 Participants |
| Primary site, No. of patients Bladder | 35 Participants | 26 Participants | 9 Participants |
| Primary site, No. of patients Renal Pelvis | 4 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 31 Participants | 22 Participants | 9 Participants |
| Sex: Female, Male Female | 9 Participants | 7 Participants | 2 Participants |
| Sex: Female, Male Male | 30 Participants | 21 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 11 | 28 / 28 |
| serious Total, serious adverse events | 4 / 11 | 15 / 28 |
Outcome results
Primary
Progression Free Survival
Time frame: Measures by CT scans following each 2 cycles of treatment and about every 8 weeks after off treatment for disease progression. Follow up for survival until time of death.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A - Cetuximab Treatment Arm | Progression Free Survival | 7.6 weeks |
| Arm B Paclitaxel and Cetuximab Combination Treatment Arm | Progression Free Survival | 16.4 weeks |
Secondary
Response Rate, Duration of Response, Time to Progression Will be Assessed With Radiographic Imaging
Time frame: Measured by CT scans after every 2 cycles of treatment (about every 8 weeks)
Population: Overall Survival
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Arm A - Cetuximab Treatment Arm | Response Rate, Duration of Response, Time to Progression Will be Assessed With Radiographic Imaging | Overall Survival | 17 weeks |
| Arm A - Cetuximab Treatment Arm | Response Rate, Duration of Response, Time to Progression Will be Assessed With Radiographic Imaging | Overall Response Rate | NA weeks |
| Arm B Paclitaxel and Cetuximab Combination Treatment Arm | Response Rate, Duration of Response, Time to Progression Will be Assessed With Radiographic Imaging | Overall Survival | 42 weeks |
| Arm B Paclitaxel and Cetuximab Combination Treatment Arm | Response Rate, Duration of Response, Time to Progression Will be Assessed With Radiographic Imaging | Overall Response Rate | 25 weeks |