Bladder Cancer
Conditions
Keywords
Locally advanced urothelial carcinoma of the bladder
Brief summary
Study participants will have been diagnosed with bladder cancer that has invaded the muscle wall of the bladder. Surgery is used to remove cancer when it is in the muscle of the bladder. Unfortunately, approximately 50% of people may have their cancer return in another location. For this reason, researchers are focusing on new chemotherapy regimens to be given before surgery (to remove the bladder) that may decrease the likelihood of cancer spreading. Paclitaxel, carboplatin and gemcitabine are chemotherapy drugs known to destroy bladder cancer cells. ABI-007 (brand name Abraxane™) is a form of the chemotherapy drug called paclitaxel. Standard paclitaxel is formulated with ethanol and a substance called Cremophor EL (polyoxyethylated castor oil). However, these additives are felt to contribute to the side effects (possibly severe) associated with paclitaxel. ABI-007 does not contain these additives and may deliver more drug to tumor cells. ABI-007 is approved by the United States Food and Drug Administration (FDA) in the treatment of metastatic (advanced) breast cancer, and is being evaluated in other cancers in research studies. This study will evaluate the safety and efficacy of the combination of ABI-007, carboplatin and gemcitabine in the treatment of bladder cancer prior to surgery to remove the bladder.
Interventions
DRUGABI-007
ABI-007 will be administered at a dose of 260 mg/m2 over a 30 min IV infusion on day 1 of each 21 day cycle.
DRUGCarboplatin
Carboplatin will be administered at a dose of TARGET AUC=5 over a 15 min IV infusion of day 1 of each 21 day cycle.
DRUGGemcitabine
Gemcitabine will be administered at a dose of 800 mg/m2 over a 30 min IV infusion on days 1 and 8 of each 21 day cycle.
PROCEDURERadical Cystectomy
Sponsors
Celgene Corporation
University of Michigan Rogel 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
* Histologically proven locally advanced (T2-4,N0,M0 or Tany,N1-3,M0) urothelial carcinoma of the bladder and be candidates for cystectomy following chemotherapy. Tumor specimens must be available for assay of molecular markers (correlative research). * Performance status of 0, 1 or 2 by Eastern Cooperative Oncology Group (ECOG) criteria. * Serum creatinine \<2.0 mg/dl and/or creatinine clearance \>40 ml/min. * Granulocyte count \> 1,500/mm3, platelet \> 100,000/mm3, and hemoglobin \> 9.0 g/dl. * Adequate liver functions: AST and ALT \< 2.5 X upper limit of normal, alkaline phosphatase \< 2.5 X upper limit of normal, and bilirubin \< 1.5 mg/dl. * Pre-existing peripheral neuropathy \> grade 2 * Recovered from any effects of surgery. * Women/men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method. Women with reproductive potential must have a negative pregnancy test.
Exclusion criteria
* Prior systemic or intra-arterial chemotherapy and rior radiotherapy. (intravesical chemotherapy allowed.) * Pre-existing peripheral neuropathy \> grade 2 * Prior malignancy \[except for adequately treated basal cell (or squamous cell) skin cancer, in situ cervical cancer or other cancer for which the patient has been disease free for 2 years\] * Unresolved bacterial infection requiring active treatment with antibiotics. (Treatment may begin at the conclusion of antibiotic therapy.) * Pregnant or lactating women may not participate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Complete Pathologic Response After 3 Cycles of Treatment | 63 days (post 3 cycles) | The rate of pathologic complete response (pT0) following three 21 day cycles of neoadjuvant ABI-007, carboplatin and gemcitabine was determined. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Neoadjuvant ABI-007, Carboplatin, and Gemcitabine Neoadjuvant ABI-007 (260 mg/m\^2) on day 1, Carboplatin (Target AUC \[Area under the curve\] =5) on day 1, and Gemcitabine (800 mg\^m2) on days 1 and 8, every 21 days. | 29 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 1 |
| Overall Study | Patient Declined Surgery | 1 |
| Overall Study | Patient had unresectable disease | 1 |
| Overall Study | Received different ABI-007 schedule | 3 |
Baseline characteristics
| Characteristic | Neoadjuvant ABI-007, Carboplatin, and Gemcitabine |
|---|---|
| Adjacent Carcinoma in Situ Present No | 13 participants |
| Adjacent Carcinoma in Situ Present Yes | 16 participants |
| Age, Continuous | 66 years |
| Angiolymphatic Invasion Present No | 20 participants |
| Angiolymphatic Invasion Present Yes | 9 participants |
| Clinical Disease Stage T2N0 | 18 participants |
| Clinical Disease Stage T2N1 | 2 participants |
| Clinical Disease Stage T2N2 | 1 participants |
| Clinical Disease Stage T3N0 | 6 participants |
| Clinical Disease Stage T4N0 | 2 participants |
| Hydronephrosis Present No | 21 participants |
| Hydronephrosis Present Yes | 8 participants |
| Mixed Histological Features Present 10% Plasmacytoid, 10% Signet Ring | 1 participants |
| Mixed Histological Features Present 10% Spindle | 1 participants |
| Mixed Histological Features Present 20% Glandular | 1 participants |
| Mixed Histological Features Present 5% Squamous | 1 participants |
| Mixed Histological Features Present 70% Plasmacytoid, 5% Sarcomatoid | 1 participants |
| Mixed Histological Features Present Micropapillary | 1 participants |
| Mixed Histological Features Present Micropapillary and Nested | 1 participants |
| Mixed Histological Features Present Nested | 3 participants |
| Mixed Histological Features Present None | 19 participants |
| Performance Status (ECOG) 0 | 17 participants |
| Performance Status (ECOG) 1 | 12 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 29 / 29 |
| serious Total, serious adverse events | 26 / 29 |
Outcome results
Primary
Percentage of Patients With Complete Pathologic Response After 3 Cycles of Treatment
The rate of pathologic complete response (pT0) following three 21 day cycles of neoadjuvant ABI-007, carboplatin and gemcitabine was determined.
Time frame: 63 days (post 3 cycles)
Population: 29 patients were enrolled. 26 of the 29 patients received the planned 3 cycles. 22 of the 26 patients had a cystectomy and were evaluable for the primary endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Neoadjuvant ABI-007, Carboplatin, and Gemcitabine | Percentage of Patients With Complete Pathologic Response After 3 Cycles of Treatment | 27.3 percentage of patients |