November 2012: Clinical Trials in Progress for Urologic Cancers

Bladder Cancer

Neoadjuvant dose-dense gemcitabine and cisplatin for bladder cancer

Sponsor: Fox Chase Cancer Center

ClinicalTrials.gov Identifier: NCT01611662

This single-arm phase II study will test the use of neoadjuvant dose-dense gemcitabine and cisplatin in patients with muscle-invasive bladder cancer who plan to undergo cystectomy with curative intent. An initial transurethral biopsy tissue may be obtained at an outside institution but must be confirmed by pathologic review at a study site. Patients will undergo radiographic staging before the start of chemotherapy and after the completion of chemotherapy and surgery. Patients will continue on surveillance follow-up per National Comprehensive Cancer Network guidelines following surgery for a total of 5 years from study enrollment or until death. Treatment with 3 cycles of dose-dense gemcitabine and cisplatin will be administered on an inpatient or outpatient basis. The primary outcome measure is the rate of complete response at cystectomy. Secondary outcome measures include treatment tolerability, overall survival (OS), and relapse-free survival. The investigators will also analyze molecular markers of chemotherapy resistance in tissue specimens from cystectomy and transurethral resection of bladder tumor specimens, when available, in order to gauge their predictability for chemotherapy efficacy and survival.

The Trials in Progress section is intended to stimulate discussion about ongoing clinical trials and to promote collaboration across the urology community. Urologists in Cancer Care presents summaries of ongoing research relating to a variety of urologic cancers.

Docetaxel and lapatinib for metastatic transitional cell carcinoma of the bladder

Sponsor: University of Southern California/Norris Comprehensive Cancer Center

ClinicalTrials.gov Identifier: NCT01382706

Prostate Cancer

This phase II study will assess the efficacy of 1250 mg of lapatinib ditosylate combined with docetaxel in patients with metastatic, previously treated transitional cell carcinoma of the bladder. Individuals are eligible provided they have locally recurrent or advanced, nonresectable or stage IV transitional cell carcinoma and have undergone prior platinum salt-based chemotherapy for their disease. Patients are also required to have tumor tissue available for evaluation for epidermal growth factor receptor and human epidermal growth factor receptor 2/neu status. Study participants will receive docetaxel IV over one hour on day 1 and lapatinib ditosylate PO daily for 21 days; the regimen is repeated every 21 days until disease progression or unacceptable toxicity. The primary outcome measure is progression-free survival (PFS). Secondary outcome measures include objective response rate (ORR), OS, and treatment safety and tolerability.Cabazitaxel versus standard treatment for metastatic castration-resistant prostate cancer

Sponsor: sanofi-aventis

ClinicalTrials.gov Identifier: NCT01308567

This phase III study will test whether first-line cabazitaxel in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer (mCRPC) is superior to docetaxel. Both treatment groups will receive concurrent prednisone. Cabazitaxel is a novel taxane active in D-sensitive and -resistant tumor models. Docetaxel/prednisone as first-line chemotherapy in patients with mCRPC is the current standard of care; however, treatment is not curative, and D-resistant disease typically develops. Patients with ECOG performance status of 0-2, histologically/cytologically confirmed metastatic prostate adenocarcinoma with no prior chemotherapy, and with disease progression following medical or surgical castration are eligible. The primary endpoint is OS. Secondary endpoints include PFS, radiologic PFS, tumor response in measurable disease, prostate-specific antigen (PSA) response and PSA PFS, pain response and pain PFS, time to occurrence of any skeletal-related events, safety profile, and health-related quality of life. Cabazitaxel pharmacokinetics and pharmacogenomics will be assessed in patient subgroups.

Neoadjuvant MDV3100 for prostate cancer

Sponsor: Medivation, Inc and Astellas Pharma, Inc

ClinicalTrials.gov Identifier: NCT01547299

This phase II study will test the effect of neoadjuvant androgen receptor (AR) blockade with AR inhibition alone using MDV3100 or combined with maximal suppression of androgens involving MDV3100 plus leuprolide and dutasteride. MDV3100 is a potent AR-signaling inhibitor (ARSI) that inhibits AR signaling via three mechanisms: inhibition of androgen binding to AR, inhibition of AR nuclear translocation, and inhibition of nuclear AR-DNA binding. The study population includes men with treatment-naïve, localized prostate cancer who are candidates for radical prostatectomy and have either a PSA greater than 10 ng/mL or Gleason score of 7 (4 + 3) or higher with 3 or more cores containing tumor and no evidence of metastatic/nodal disease. All patients receive MDV3100 (160 mg/day orally); those randomized to MDV3100 plus leuprolide and dutasteride therapy also receive leuprolide (22.5 mg IM every 3 months) and dutasteride (0.5 mg/day orally). The primary efficacy endpoint is pathological complete response rate at the time of radical prostatectomy.

Orteronel for advanced prostate cancer

Sponsor: Millennium Pharmaceuticals, Inc

ClinicalTrials.gov Identifier: NCT01193257; C21005

This phase III study will compare the investigational agent orteronel (TAK-700) plus prednisone versus placebo plus prednisone in patients with mCRPC that has progressed during or following docetaxelbased therapy. Orteronel is a selective inhibitor of 17,20-lyase, a key enzyme in the testosterone synthesis pathway. In order to be eligible, patients must have evidence of disease progression during or after receiving a total of 360 mg/m² docetaxel or more within a 6-month period. Patients who cannot tolerate docetaxel or who have progressive disease before receiving 360 mg/m² or more are also eligible if they have received at least 225 mg/m² of docetaxel within a 6-month period and satisfy the other inclusion criteria, which include radiographically documented metastatic disease and baseline testosterone level lower than 50 ng/dL following surgical or medical castration. The primary endpoint is OS. Secondary endpoints include radiographic PFS, PSA decrease of 50% or greater at 12 weeks, pain response at 12 weeks, safety, time to PSA progression, ORR by RECIST, circulating tumor cell and endocrine marker changes, and patientreported outcomes. Tumor specimens will be analyzed for biomarkers that may predict orteronel antitumor activity.

Hormone therapy, radiation therapy, and TAK-700 for prostate cancer

Sponsor: Radiation Therapy Oncology Group

ClinicalTrials.gov Identifier: NCT01546987

Renal Cancer

This phase III study will compare standard treatment involving androgen-deprivation therapy with radiotherapy versus standard treatment with the addition of 24 months of steroid 17alpha-monooxygenase TAK- 700 in men with clinically localized prostate cancer with unfavorable prognostic features. TAK-700 (orteronel) is a novel, selective, and potent inhibitor of 17,20-lyase. In order to be eligible, patients must have a histologically confirmed diagnosis of adenocarcinoma of the prostate within 180 days prior to enrollment with a high risk of recurrence as determined by one of the following combinations: Gleason Score (GS) ≥ 9, PSA ≤ 150 ng/mL, any T stage; GS ≥ 8, PSA < 20 ng/mL, T stage ≥ T2; GS ≥ 8, PSA ≥ 20-150 ng/mL, any T stage; or GS ≥ 7, PSA ≥ 20-150 ng/mL, any T stage. The primary outcome measure is OS. Investigators intend to recruit 900 patients.Everolimus alternating with sunitinib for renal cancer

This phase II study is aiming to determine the activity and safety of an alternating regimen of two therapies with different targets (sunitinib and everolimus) in patients with advanced renal cell carcinoma (RCC). Individuals are eligible provided they have RCC with a clear-cell component, metastatic or locally advanced disease not suitable for resection, ECOG performance status of 0-1, and low or intermediate Memorial Sloan-Kettering Cancer Center prognostic score. Treatment is administered in 12-week cycles consisting of 4 weeks of sunitinib 50 mg daily followed by 2 weeks rest, followed by 5 weeks of everolimus (10 mg daily), followed by 1 week rest. The primary endpoint is the status of being alive and progression-free by RECIST 1.1 criteria 6 months after enrollment. Participants who stop one drug because of toxicity or disease progression on or before the 6-month assessment will continue the other drug until subsequent progression or unacceptable toxicity on the second drug.

Everolimus after surgery for renal cancer

Sponsor: Southwest Oncology Group

ClinicalTrials.gov Identifier: NCT01120249

This phase III study will evaluate everolimus in patients with RCC who have undergone radical or partial nephrectomy, including removal of all clinically positive nodes. Study participants will be stratified according to pathologic stage (intermediate high risk vs very high risk), histologic subtype (clear cell vs non-clear cell), and performance status (0 vs 1), and then randomized to 1 of 2 treatment arms. One group of patients will receive oral everolimus once daily on days 1 though 42, and treatment is repeated every 6 weeks for 9 courses in the absence of disease progression or unacceptable toxicity. The other group of patients will receive oral placebo once daily on days 1 through 42, and treatment is repeated every 6 weeks for 9 courses in the absence of disease progression or unacceptable toxicity. The primary endpoint is recurrence-free survival. Secondary endpoints include OS and toxicity. After the end of treatment, patients are followed up every 6 months for 2 years, and then annually for 8 years.