Bladder Cancer
Conditions
Keywords
transitional cell carcinoma of the bladder, stage II bladder cancer, stage III bladder cancer, stage IV bladder cancer
Brief summary
RATIONALE: Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving sunitinib before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. PURPOSE: This phase II trial is studying the side effects and how well sunitinib works in treating patients with locally advanced bladder cancer.
Detailed description
OBJECTIVES: Primary * To determine the pathologic complete response rate of sunitinib malate in patients with muscle-invasive locally advanced transitional cell carcinoma (TCC) of the bladder. * To evaluate the safety and tolerability of sunitinib malate administered prior to radical cystectomy, including surgical outcome and surgical complications. Secondary * To determine the clinical effects of sunitinib malate administered prior to radical cystectomy and bilateral lymph node dissection, including overall response rate using RECIST defined criteria, cytology, and histologic appearance of surgical specimen as well as time to progression. Tertiary * To assess pre-treatment tissue baseline angiogenic markers and to evaluate the magnitude of the difference among these variables with post-treatment tumor tissue after neoadjuvant sunitinib malate. * To evaluate the effects of sunitinib malate on immunosuppressive regulatory T cells. OUTLINE: Patients receive oral sunitinib malate once daily in weeks 1-4 (1 course). Patients undergo restaging within 1 week prior to surgery and then undergo radical cystectomy and bilateral lymph node dissection on day 42. Patients achieving a complete pathologic response at the time of surgery may receive 6 more courses of adjuvant sunitinib malate beginning 28 days after surgery at the discretion of the treating physician. Patients found to have high-risk features (i.e. pT3 or greater tumor and evidence of disease in any of the lymph nodes resected) are offered standard adjuvant systemic chemotherapy at the discretion of the treating physician. Tumor tissue from pretreatment biopsy and radical cystectomy will be tested for VEGFR-1, VEGFR-2 and PDGF-R expression by IHC. Samples are also analyzed for quantification of cell proliferation and apoptosis and immunosuppressive regulatory T cells (T-reg) and T-reg functions. After completion of study treatment, patients are followed at 28 days after surgery.
Interventions
DRUGsunitinib malate
50mg PO daily 4 weeks on -2 weeks off
Sponsors
National Cancer Institute (NCI)
Case Comprehensive 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
DISEASE CHARACTERISTICS: Inclusion criteria: * Histological confirmed transitional cell carcinoma (TCC) of the bladder * Patients with mixed tumors (i.e., tumors containing elements of squamous cell or adenocarcinoma) are eligible * Patients with pure non-transitional cell carcinomas are not eligible * Meets 1 of the following staging criteria: * Tumors ≥ cT2 * Patients with cT2 lesions must have either a bulky or fixed lesion at the time of physical examination and/or scans * Any cT stage with nodal-positive disease (documented by scans) * Patients with (+) N1-N3 disease are eligible * Candidate for radical cystectomy in ≥ 8 weeks while neoadjuvant sunitinib malate is administered
Exclusion criteria
* Any evidence of distant metastasis (excluding pelvic or retroperitoneal lymph nodes) PATIENT CHARACTERISTICS: Inclusion criteria: * ECOG performance status (PS) 0-1 (Karnofsky PS greater than 70%) * Absolute neutrophil count ≥ 1,500/mcL * Platelet count ≥ 100,000/mcL * Hemoglobin ≥ 8.5 g/dL * Total bilirubin ≤ 1.5 times institutional upper limit of normal (ULN) * AST and ALT ≤ 3.5 times ULN * Alkaline phosphatase ≤ 2.5 times ULN (≤ 10 times ULN in presence of bone metastasis) * Serum calcium ≤ 12 mg/dL * Creatinine ≤ 1.5 times ULN * INR ≤ 1.5 (except for patients receiving warfarin therapy) * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 3 months after completion of study treatment * Disease-free of prior malignancies for ≥ 5 years except for currently treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic Complete Response Rate of Sunitinib | at 6 weeks | Number of participants who at the time of cystectomy, to have no evidence of tumor grossly and microscopically on routine Hematoxylin and Eosin stain (H&E) (pathologic complete response or P0) will be defined as responders. All cases will be defined as responders (P0) or non-responders based on the presence of residual tumor. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. Progression (PD): At least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum LD since the treatment started. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate Treatment to Surgical Complication and Morbidity | following surgery at 6 weeks | Determine if surgical morbidity was increased from time of last dose to time of surgery is defined as the number of subjects with increase non-ileus related morbidity due to treatment drug during the 2 week rest period. |
| Time to Progression | at 4 weeks post-surgery | Time to progression will be measured as the time from when the patient started treatment to the time the patient is first recorded as having disease progression or the date of death if the patient dies due to causes other than disease progression. |
Countries
United States
Participant flow
Recruitment details
Eleven patients were entered into the trial between 9/07 and 12/09 from medical clinic. Two patients were considered ineligible and received no treatment.
Participants by arm
| Arm | Count |
|---|---|
| Sunitinib Malate Drug
sunitinib malate : 50mg PO daily 4 weeks on -2 weeks off | 9 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
| Overall Study | Refused surgery | 1 |
Baseline characteristics
| Characteristic | Sunitinib Malate |
|---|---|
| Age, Continuous | 62 years |
| Region of Enrollment United States | 9 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 7 / 9 |
| other Total, other adverse events | 9 / 9 |
| serious Total, serious adverse events | 4 / 9 |
Outcome results
Primary
Pathologic Complete Response Rate of Sunitinib
Number of participants who at the time of cystectomy, to have no evidence of tumor grossly and microscopically on routine Hematoxylin and Eosin stain (H&E) (pathologic complete response or P0) will be defined as responders. All cases will be defined as responders (P0) or non-responders based on the presence of residual tumor. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. Progression (PD): At least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum LD since the treatment started.
Time frame: at 6 weeks
Population: Participants who completed treatment and surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sunitinib Malate | Pathologic Complete Response Rate of Sunitinib | 0 Participants |
Secondary
Evaluate Treatment to Surgical Complication and Morbidity
Determine if surgical morbidity was increased from time of last dose to time of surgery is defined as the number of subjects with increase non-ileus related morbidity due to treatment drug during the 2 week rest period.
Time frame: following surgery at 6 weeks
Population: Participants who received treatment and surgery.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sunitinib Malate | Evaluate Treatment to Surgical Complication and Morbidity | 0 Participants |
Secondary
Time to Progression
Time to progression will be measured as the time from when the patient started treatment to the time the patient is first recorded as having disease progression or the date of death if the patient dies due to causes other than disease progression.
Time frame: at 4 weeks post-surgery
Population: Data not collected.