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.
Neoadjuvant dose-dense gemcitabine and cisplatin for bladder cancer
Docetaxel and lapatinib for metastatic transitional cell carcinoma of the bladder
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.
Sponsor: Fox Chase Cancer Center
ClinicalTrials.gov Identifier: NCT01611662
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.
Sponsor: University of Southern California/Norris Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01382706
Cabazitaxel versus standard treatment for metastatic castration-resistant prostate cancer
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.
ClinicalTrials.gov Identifier: NCT01308567
Neoadjuvant MDV3100 for prostate cancer
Orteronel for advanced prostate cancer
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.
Sponsor: Medivation, Inc and Astellas Pharma, Inc
ClinicalTrials.gov Identifier: NCT01547299
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.
Sponsor: Millennium Pharmaceuticals, Inc
ClinicalTrials.gov Identifier: NCT01193257; C21005