Neoadjuvant ABI-007, Carboplatin and Gemcitabine in Locally Advanced Bladder Cancer
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
Drug: ABI-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.
Drug: Carboplatin
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.
Drug: Gemcitabine
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.
Procedure: Radical Cystectomy
|
Outcome Measures
Primary Outcome Measures
- 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.
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Michigan | Ann Arbor | Michigan | United States | 48109 |
Sponsors and Collaborators
- University of Michigan Rogel Cancer Center
- Celgene Corporation
Investigators
- Principal Investigator: David C Smith, MD, University of Michigan
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- UMCC 2007.061
- HUM 13486
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Neoadjuvant ABI-007, Carboplatin, and Gemcitabine |
|---|---|
| Arm/Group Description | 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. |
| Period Title: Overall Study | |
| STARTED | 29 |
| COMPLETED | 22 |
| NOT COMPLETED | 7 |
Baseline Characteristics
| Arm/Group Title | Neoadjuvant ABI-007, Carboplatin, and Gemcitabine |
|---|---|
| Arm/Group Description | 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. |
| Overall Participants | 29 |
| Age (years) [Median (Full Range) ] | |
| Median (Full Range) [years] |
66
|
| Sex: Female, Male (Count of Participants) | |
| Female |
7
24.1%
|
| Male |
22
75.9%
|
| Performance Status (ECOG) (participants) [Number] | |
| 0 |
17
58.6%
|
| 1 |
12
41.4%
|
| Clinical Disease Stage (participants) [Number] | |
| T2N0 |
18
62.1%
|
| T2N1 |
2
6.9%
|
| T2N2 |
1
3.4%
|
| T3N0 |
6
20.7%
|
| T4N0 |
2
6.9%
|
| Hydronephrosis Present (participants) [Number] | |
| Yes |
8
27.6%
|
| No |
21
72.4%
|
| Angiolymphatic Invasion Present (participants) [Number] | |
| Yes |
9
31%
|
| No |
20
69%
|
| Adjacent Carcinoma in Situ Present (participants) [Number] | |
| Yes |
16
55.2%
|
| No |
13
44.8%
|
| Mixed Histological Features Present (participants) [Number] | |
| 70% Plasmacytoid, 5% Sarcomatoid |
1
3.4%
|
| 10% Plasmacytoid, 10% Signet Ring |
1
3.4%
|
| 5% Squamous |
1
3.4%
|
| 10% Spindle |
1
3.4%
|
| 20% Glandular |
1
3.4%
|
| Nested |
3
10.3%
|
| Micropapillary |
1
3.4%
|
| Micropapillary and Nested |
1
3.4%
|
| None |
19
65.5%
|
Outcome Measures
| Title | Percentage of Patients With Complete Pathologic Response After 3 Cycles of Treatment |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Neoadjuvant ABI-007, Carboplatin, and Gemcitabine |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 22 |
| Number (95% Confidence Interval) [percentage of patients] |
27.3
|
Adverse Events
| Time Frame | ||
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Neoadjuvant ABI-007, Carboplatin, and Gemcitabine | |
| Arm/Group Description | 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. | |
All Cause Mortality |
||
| Neoadjuvant ABI-007, Carboplatin, and Gemcitabine | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Neoadjuvant ABI-007, Carboplatin, and Gemcitabine | ||
| Affected / at Risk (%) | # Events | |
| Total | 26/29 (89.7%) | |
| Blood and lymphatic system disorders | ||
| Anemia | 1/29 (3.4%) | 1 |
| Neutropenia | 22/29 (75.9%) | 34 |
| Thrombocytopenia | 9/29 (31%) | 9 |
| Febrile neutropenia | 4/29 (13.8%) | 4 |
| Gastrointestinal disorders | ||
| Dehydration | 1/29 (3.4%) | 1 |
| General disorders | ||
| Flu-like syndrome | 1/29 (3.4%) | 1 |
| Infections and infestations | ||
| Infection with Grade 3 or 4 neutrophils | 1/29 (3.4%) | 1 |
| Infection with normal ANC or Grade 1 or 2 neutrophils | 1/29 (3.4%) | 1 |
| Nervous system disorders | ||
| Hemorrhage, CNS | 1/29 (3.4%) | 1 |
| Renal and urinary disorders | ||
| Renal failure | 1/29 (3.4%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||
| Adult Respiratory Distress Syndrome (ARDS) | 1/29 (3.4%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| Neoadjuvant ABI-007, Carboplatin, and Gemcitabine | ||
| Affected / at Risk (%) | # Events | |
| Total | 29/29 (100%) | |
| Blood and lymphatic system disorders | ||
| Anemia | 19/29 (65.5%) | 32 |
| Leukopenia | 19/29 (65.5%) | 37 |
| Lymphopenia | 2/29 (6.9%) | 2 |
| Neutropenia | 25/29 (86.2%) | 59 |
| Thrombocytopenia | 25/29 (86.2%) | 46 |
| Cardiac disorders | ||
| Hypertension | 2/29 (6.9%) | 2 |
| Gastrointestinal disorders | ||
| Anorexia | 11/29 (37.9%) | 11 |
| Constipation | 8/29 (27.6%) | 9 |
| Dehydration | 3/29 (10.3%) | 3 |
| Diarrhea | 9/29 (31%) | 9 |
| Nausea | 15/29 (51.7%) | 18 |
| Taste alteration (dysgeusia) | 3/29 (10.3%) | 3 |
| Vomiting | 4/29 (13.8%) | 5 |
| General disorders | ||
| Fatigue (asthenia, lethargy, malaise) | 25/29 (86.2%) | 32 |
| Rigors/chills | 2/29 (6.9%) | 2 |
| Weight loss | 2/29 (6.9%) | 2 |
| Edema: limb | 2/29 (6.9%) | 2 |
| Pain - Other (Specify) | 4/29 (13.8%) | 8 |
| Infections and infestations | ||
| Febrile neutropenia | 4/29 (13.8%) | 4 |
| Infection with normal ANC or Grade 1 or 2 neutrophils | 2/29 (6.9%) | 2 |
| Metabolism and nutrition disorders | ||
| ALT, SGPT (serum glutamic pyruvic transaminase) | 7/29 (24.1%) | 8 |
| AST, SGOT(serum glutamic oxaloacetic transaminase) | 6/29 (20.7%) | 6 |
| Creatinine | 2/29 (6.9%) | 2 |
| Glucose, serum-high (hyperglycemia) | 9/29 (31%) | 10 |
| Musculoskeletal and connective tissue disorders | ||
| Arthritis (non-septic) | 2/29 (6.9%) | 2 |
| Muscle weakness | 5/29 (17.2%) | 5 |
| Back Pain | 4/29 (13.8%) | 4 |
| Limb Pain | 6/29 (20.7%) | 6 |
| Joint Pain | 5/29 (17.2%) | 7 |
| Muscle Pain | 7/29 (24.1%) | 8 |
| Pelvic Pain | 4/29 (13.8%) | 6 |
| Nervous system disorders | ||
| Dizziness | 3/29 (10.3%) | 3 |
| Neuropathy: sensory | 17/29 (58.6%) | 20 |
| Headache Pain | 3/29 (10.3%) | 3 |
| Renal and urinary disorders | ||
| Cystitis | 3/29 (10.3%) | 3 |
| Urinary frequency/urgency | 6/29 (20.7%) | 6 |
| Respiratory, thoracic and mediastinal disorders | ||
| Dyspnea (shortness of breath) | 4/29 (13.8%) | 4 |
| Skin and subcutaneous tissue disorders | ||
| Hair loss/alopecia (scalp or body) | 22/29 (75.9%) | 25 |
| Rash/desquamation | 5/29 (17.2%) | 6 |
| Vascular disorders | ||
| Hot flashes/flushes | 3/29 (10.3%) | 3 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. David Smith, M.D. |
|---|---|
| Organization | University of Michigan Comprehensive Cancer Center |
| Phone | 734-936-6884 |
| dcsmith@umich.edu |
- UMCC 2007.061
- HUM 13486