Clinical trial NCT00526656: Sunitinib in Treating Patients With Locally Advanced Bladder Cancer
Official title: Phase II Single Arm, Open Label, Single Institution Study of Neoadjuvant Sunitinib (SUTENT) in Patients With Muscle-Invasive Locally Advanced Transitional Cell Carcinoma of the Bladder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Bladder Cancer
Keywords: transitional cell carcinoma of the bladder
stage II bladder cancer
stage III bladder cancer
stage IV bladder cancer
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-09-10
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Pathologic Complete Response Rate of Sunitinib
timeFrame: at 6 weeks
Secondary outcomes:
measure: Evaluate Treatment to Surgical Complication and Morbidity
timeFrame: following surgery at 6 weeks
measure: Time to Progression
timeFrame: at 4 weeks post-surgery
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
name: Jorge A. Garcia, MD
role: PRINCIPAL_INVESTIGATOR
References: