Bladder Cancer
Conditions
Keywords
Bladder Cancer, Chemotherapy, Bladder Neoplasms
Brief summary
Phase I: To determine the safety, toxicity and efficacy profiles of intravesically administered Abraxane at the Maximum Tolerated Dose. To assemble tissue bank to assess molecular correlates for response to intravesical Abraxane therapy. The antibodies analyzed will include p53, p63, Stathmin, Tau and Ki67. Phase II: To evaluate the utility (potential for clinical efficacy) of Abraxane in the treatment of refractory non-muscle invasive and a subset of T2 TCC of the bladder as measured by response rate (defined as negative cytology and bladder biopsy). To further evaluate the safety and toxicity profile of intravesically administered Abraxane therapy.
Detailed description
In 2006, it is estimated that 61,420 cases of bladder cancer will be diagnosed in the United States and 13,060 people will die from the disease. This makes bladder cancer the fourth leading cause of cancer in men and the ninth leading cause of cancer in women in the United States. Non-muscle invasive bladder cancer accounts for 70 to 80 percent of these cases and the natural history can vary widely with recurrence being common. In individual cases with high-risk clinical and pathological features (Ta, Tis, and T1) the use of intravesical therapy following complete transurethral resection of the tumor has become the standard of care. However up to 50 percent of patients treated with intravesical therapy for high-risk non-muscle invasive bladder cancer will recur. Response rates to second-line intravesical therapy are 20 percent or less in this population. Innovations in the efficacy of intravesical agents also have applications within a subset of patients with muscle-invasive disease who are undergoing complete transurethral resection in conjunction with local chemotherapy.
Interventions
DRUGAbraxane
Abraxane is an anti-cancer (antineoplastic or cytotoxic) chemotherapy drug. Intravesically administered, dose escalation, 6 weekly instillations
Sponsors
Celgene Corporation
Columbia University
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have a diagnosis of transitional cell carcinoma (TCC) of the urinary bladder confirmed at the study institution. The patient must have demonstrated superficial recurrent bladder cancer refractory to standard intravesical therapy. This will include stage Ta, T1, Tis and exclude all patients with muscle invasion (T2). All patients with stage Ta will require documentation of high-grade histology. All grossly visible disease must be fully resected and pathologic stage will be confirmed at the institution where the patient is enrolled. Patients must exhibit disease recurrence after receiving some form of standard intravesical therapy, including Bacillus Calmette-Guerin (BCG), mitomycin, interferon or any combination thereof. * Age \> 18 and must be able to read, understand and sign informed consent * Performance Status: Eastern Cooperative Oncology Group (ECOG) 0,1 (See Appendix II ) * Peripheral neuropathy: must be \< grade 1 * Hematologic-Inclusion within 2 weeks of start of treatment * Absolute neutrophil count \> 1,500/mm3 * Hemoglobin \>9.0 g/dl * Platelet count \> 100,000/mm3 * Hepatic-Inclusion within 2 weeks of entry * Total Bilirubin must be within normal limits. * Adequate renal function with serum creatinine ≤ 2.0 mg/dL * Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x upper limit of normal (ULN) for the institution, Alkaline phosphatase ≤ 2.5 x ULN for the institution, unless bone metastasis is present in the absence of liver metastasis * Women of childbearing potential must have a negative pregnancy test. * All patients of childbearing potential must be willing to consent to using effective contraception, i.e., intrauterine device (IUD), Birth control pills, Depo-Provera, and condoms while on treatment and for 3 months after their participation in the study ends. * No intravesical therapy within 6 weeks of study entry * No prior radiation to the pelvis
Exclusion criteria
* Prior systemic docetaxel or paclitaxel therapy. * Any other malignancy diagnosed within 2 years of study entry (except basal or squamous cell skin cancers or non-invasive cancer of the cervix) is excluded. * Concurrent treatment with any chemotherapeutic agent. * Women who are pregnant or lactating. * History of vesicoureteral reflux or an indwelling urinary stent. * Participation in any other research protocol involving administration of an investigational agent within 3 months prior to study entry aside from the phase I segment of this study. * History of neuropathy of any cause
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) | 6 weeks | To determine the safety, toxicity and efficacy profiles of intravesically administered Abraxane at the Maximum Tolerated Dose (MTD). A DLT is defined by the National Cancer Institute Common Toxicity Criteria version 3.0 |
| Number of Participants With Complete Response (CR) or No Response (NR) After Treatment | 6 weeks | To evaluate the utility (potential for clinical efficacy) of Abraxane in the treatment of refractory superficial transitional cell carcinomas (TCC) as measured by response rate (defined as negative cytology and bladder biopsy). Patients were considered to have a complete response if they had a negative biopsy and negative cytology. All patients with positive biopsies or cytology were classified as having no response. |
Secondary
| Measure | Time frame |
|---|---|
| To Further Evaluate the Safety and Toxicity Profile of Intravesically Administered Abraxane Therapy. | 6 months |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Abraxane 150 mg Phase 1, dose level 1: Patients will receive intravesical 150 mg Abraxane by sterile urethral catheterization once weekly for six weeks. | 3 |
| Abraxane 225 mg Phase 1, dose level 2: Patients will receive intravesical 225 mg Abraxane by sterile urethral catheterization once weekly for six weeks. | 3 |
| Abraxane 300 mg Phase 1, dose level 3: Patients will receive intravesical 300 mg Abraxane by sterile urethral catheterization once weekly for six weeks. | 3 |
| Abraxane 375 mg Phase 1, dose level 4: Patients will receive intravesical 375 mg Abraxane by sterile urethral catheterization once weekly for six weeks. | 3 |
| Abraxane 450 mg Phase 1, dose level 5: Patients will receive intravesical 450 mg Abraxane by sterile urethral catheterization once weekly for six weeks. | 3 |
| Abraxane 500 mg Phase 1, dose level 6: Patients will receive intravesical 500 mg Abraxane by sterile urethral catheterization once weekly for six weeks. | 3 |
| MTD: Abraxane 500 mg Phase 2: Patients will receive the maximum tolerated dose (MTD) intravesical 500 mg Abraxane by sterile urethral catheterization once weekly for six weeks. | 28 |
| Total | 46 |
Baseline characteristics
| Characteristic | Abraxane 150 mg | Abraxane 225 mg | Abraxane 300 mg | Abraxane 375 mg | Abraxane 450 mg | Abraxane 500 mg | MTD: Abraxane 500 mg | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Customized ≥ 18 years | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 28 Participants | 46 Participants |
| Region of Enrollment United States | 3 participants | 3 participants | 3 participants | 3 participants | 3 participants | 3 participants | 28 participants | 46 participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 6 Participants | 11 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 22 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 2 / 28 |
| other Total, other adverse events | 2 / 3 | 2 / 3 | 1 / 3 | 2 / 3 | 1 / 3 | 2 / 3 | 1 / 28 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 28 |
Outcome results
Primary
Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)
To determine the safety, toxicity and efficacy profiles of intravesically administered Abraxane at the Maximum Tolerated Dose (MTD). A DLT is defined by the National Cancer Institute Common Toxicity Criteria version 3.0
Time frame: 6 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Abraxane 150 mg | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) | Grade 3 or higher local toxicity | 0 Participants |
| Abraxane 150 mg | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) | Grade 2 local toxicity | 0 Participants |
| Abraxane 150 mg | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) | Grade 1 local toxicity | 2 Participants |
| Abraxane 225 mg | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) | Grade 2 local toxicity | 0 Participants |
| Abraxane 225 mg | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) | Grade 1 local toxicity | 2 Participants |
| Abraxane 225 mg | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) | Grade 3 or higher local toxicity | 0 Participants |
| Abraxane 300 mg | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) | Grade 3 or higher local toxicity | 0 Participants |
| Abraxane 300 mg | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) | Grade 1 local toxicity | 1 Participants |
| Abraxane 300 mg | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) | Grade 2 local toxicity | 0 Participants |
| Abraxane 375 mg | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) | Grade 2 local toxicity | 0 Participants |
| Abraxane 375 mg | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) | Grade 1 local toxicity | 3 Participants |
| Abraxane 375 mg | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) | Grade 3 or higher local toxicity | 0 Participants |
| Abraxane 450 mg | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) | Grade 2 local toxicity | 0 Participants |
| Abraxane 450 mg | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) | Grade 1 local toxicity | 0 Participants |
| Abraxane 450 mg | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) | Grade 3 or higher local toxicity | 0 Participants |
| Abraxane 500 mg | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) | Grade 1 local toxicity | 3 Participants |
| Abraxane 500 mg | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) | Grade 3 or higher local toxicity | 0 Participants |
| Abraxane 500 mg | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) | Grade 2 local toxicity | 0 Participants |
| MTD: Abraxane 500 mg | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) | Grade 3 or higher local toxicity | 0 Participants |
| MTD: Abraxane 500 mg | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) | Grade 2 local toxicity | 5 Participants |
| MTD: Abraxane 500 mg | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) | Grade 1 local toxicity | 4 Participants |
Primary
Number of Participants With Complete Response (CR) or No Response (NR) After Treatment
To evaluate the utility (potential for clinical efficacy) of Abraxane in the treatment of refractory superficial transitional cell carcinomas (TCC) as measured by response rate (defined as negative cytology and bladder biopsy). Patients were considered to have a complete response if they had a negative biopsy and negative cytology. All patients with positive biopsies or cytology were classified as having no response.
Time frame: 6 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abraxane 150 mg | Number of Participants With Complete Response (CR) or No Response (NR) After Treatment | NR | 2 participants |
| Abraxane 150 mg | Number of Participants With Complete Response (CR) or No Response (NR) After Treatment | CR | 1 participants |
| Abraxane 225 mg | Number of Participants With Complete Response (CR) or No Response (NR) After Treatment | CR | 3 participants |
| Abraxane 225 mg | Number of Participants With Complete Response (CR) or No Response (NR) After Treatment | NR | 0 participants |
| Abraxane 300 mg | Number of Participants With Complete Response (CR) or No Response (NR) After Treatment | CR | 0 participants |
| Abraxane 300 mg | Number of Participants With Complete Response (CR) or No Response (NR) After Treatment | NR | 3 participants |
| Abraxane 375 mg | Number of Participants With Complete Response (CR) or No Response (NR) After Treatment | NR | 2 participants |
| Abraxane 375 mg | Number of Participants With Complete Response (CR) or No Response (NR) After Treatment | CR | 1 participants |
| Abraxane 450 mg | Number of Participants With Complete Response (CR) or No Response (NR) After Treatment | NR | 3 participants |
| Abraxane 450 mg | Number of Participants With Complete Response (CR) or No Response (NR) After Treatment | CR | 0 participants |
| Abraxane 500 mg | Number of Participants With Complete Response (CR) or No Response (NR) After Treatment | CR | 0 participants |
| Abraxane 500 mg | Number of Participants With Complete Response (CR) or No Response (NR) After Treatment | NR | 3 participants |
| MTD: Abraxane 500 mg | Number of Participants With Complete Response (CR) or No Response (NR) After Treatment | NR | 18 participants |
| MTD: Abraxane 500 mg | Number of Participants With Complete Response (CR) or No Response (NR) After Treatment | CR | 10 participants |
Secondary
To Further Evaluate the Safety and Toxicity Profile of Intravesically Administered Abraxane Therapy.
Time frame: 6 months
Population: Data were not collected.