Sunitinib in Treating Patients With Locally Advanced Bladder Cancer

Case Comprehensive Cancer Center (Case CCC)

Status and phase

Completed

Phase 2

Conditions

Bladder Cancer

Treatments

Drug: sunitinib malate

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00526656

GA6180CV (Other Grant/Funding Number)

CASE24806

P30CA043703 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment

9 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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

Exclusion criteria:

NCI CTCAE grade 3 hemorrhage within 4 weeks of starting study treatment
Any of the following within 6 months prior to study drug administration:
- Myocardial infarction
- Severe/unstable angina
- Coronary/peripheral artery bypass graft
- Symptomatic congestive heart failure
- Cerebrovascular accident or transient ischemic attack
- Pulmonary embolism
Ongoing cardiac dysrhythmias of NCI CTCAE grade ≥ 2, atrial fibrillation of any grade, or prolongation of the QTc interval to > 450 msec for males or > 470 msec for females
Hypertension that cannot be controlled by medications
Known HIV or AIDS-related illness
Infectious hepatitis type A, B, or C
Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

Other systemic chemotherapy must have been completed at least 5 years prior to enrollment
No prior systemic chemotherapy for bladder cancer
No other approved or investigational anticancer treatment will be permitted during the study period, including chemotherapy, biological response modifiers, hormone therapy, surgery, palliative radiotherapy, or immunotherapy
No other investigational drug may be used during treatment on this protocol
No concurrent participation in another clinical trial

Exclusion criteria:

Prior intravesical chemotherapy or immunotherapy
Prior treatment with any other antiangiogenic therapy (including immunomodulatory agents such as thalidomide and lenalidomide and anti-VEGF therapy with agents such as bevacizumab, sunitinib malate, and sorafenib tosylate)
Prior surgery, radiotherapy, or systemic therapy within 4 weeks of starting the study treatment