Urologic Trials in Progress

Genitourinary Cancer

PREDICT looking for predictive biomarkers in renal cell carcinoma

The PREDICT (Personalized RNA Interference to Enhance the Delivery of Individualized Cytotoxic and Targeted Therapeutics) Consortium is conducting multicenter, single-arm phase II trials of everolimus (EPREDICT) or sunitinib (S-PREDICT) administered around the time of the nephrectomy in patients with untreated metastatic renal cell carcinoma (mRCC). Although inhibitors of the vascular endothelial growth factor receptor (VEGFR) and the mammalian target of rapamycin (mTOR) have transformed mRCC therapy, predictive biomarkers have not been identified. The researchers plan to analyze the molecular markers of paired biopsies before and after treatment and compare them to clinical data to find predictive biomarkers. Sunitinib and everolimus will be given before and after nephrectomy and will continue until disease progression at metastatic sites. The primary clinical endpoint is the safety of peri-nephrectomy everolimus and sunitinib. Secondary endpoints include efficacy and biomarker measurements. The researchers hope to recruit 60 patients per trial.

Sponsor: The PREDICT Consortium

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

Everolimus alternating with sunitinib for renal cancer

Sponsor: The University of Sydney; Novartis Australian New Zealand Clinical Trials Registry

Identifier: ACTRN12609000643279

Prostate 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 of rest. The primary endpoint is the status of being alive and progression- free by Response Evaluation Criteria in Solid Tumors (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. Abstract TPS4681. Oral MDV3100 in chemotherapy-naïve patients with metastatic prostate cancer

Sponsor: Medivation, Inc

ClinicalTrials.gov Identifier: NCT01212991

Renal Cancer

Sunitinib or placebo for patients at high risk of recurrent renal cell cancer

This phase III study is comparing sunitinib with placebo as adjuvant treatment in patients at high risk of recurrent kidney cancer per modified University of California Los Angeles Integrated Staging System (UISS) criteria after surgery. Subjects are Eastern Cooperative Oncology Group (ECOG) grade 0 to 2 and have predominant clear-cell histology. In addition, they have not undergone prior anticancer treatment but have had their kidney tumor removed with no evidence of macroscopic disease following surgery. Approximately 720 patients will be randomized to sunitinib 50 mg PO or placebo on a 4/2 schedule: 4 weeks on, 2 weeks off for 1 year or until disease recurrence or occurrence of a secondary malignancy, significant toxicity, or withdrawal of consent. The primary outcome measure is disease-free survival. Investigators will also determine overall survival, safety, tolerability, and patient-reported outcomes.

Sponsor: Pfizer

ClinicalTrials.gov Identifier: NCT00375674

This phase III study will test the efficacy and safety of the novel androgen signaling inhibitor MDV3100 in chemotherapy-naïve patients who have progressive metastatic prostate cancer despite androgendeprivation therapy (ADT) as defined by rising prostate-specific antigen levels or progressive soft-tissue or bony disease. Study participants are asymptomatic or mildly symptomatic from prostate cancer. The primary outcome measures are overall survival and progression-free survival. Secondary outcome measures are time to first skeletal-related event and time to initiation of cytotoxic chemotherapy. An estimated 1680 men will participate in the study, which has a targeted primary completion date of September 2014.

Axitinib (AG-013736) for the treatment of metastatic renal cell cancer

This phase III study is designed to determine whether axitinib is superior to sorafenib in delaying tumor progression in patients with metastatic renal cell cancer. Participants are required to have histologically documented metastatic renal cell cancer with a component of clear-cell histology and evidence of measurable disease. They cannot have received prior systemic first-line therapy or must have progressive disease per Response Evaluation Criteria In Solid Tumors (RECIST) - version 1.0 after one prior systemic first-line regimen for metastatic disease containing sunitinib, cytokine(s), or both. Subjects will be randomized to axitinib at a starting dose of 5 mg bid with continuous dosing or sorafenib at a dose of 400 mg bid with continuous dosing. The primary outcome measure is progression-free survival. Secondary outcome measures include overall survival, response rate, safety and tolerability, duration of response, kidney-specific symptoms, and health status.

Sponsor: Pfizer

ClinicalTrials.gov Identifier: NCT00920816

Supportive Care

Radiopharmaceuticals and zoledronic acid for bone metastases

This phase III study is testing whether zoledronic acid, vitamin D, and calcium is superior to zoledronic acid, vitamin D, and calcium plus either strontium 89 or samarium 153 in the delaying of bone problems in patients with bone metastases from lung, breast, and prostate cancer. The primary outcome measure is the time to development of a malignant skeletal-related event (SRE). Secondary outcome measures include SRE at 1 year, overall survival, changes in quality of life, changes in pain control, and the utility and cost-effectiveness of the use of radiopharmaceuticals and bisphosphonates. The study is aiming to recruit about 352 patients, with an estimated primary completion date of March 2013.

Sponsor: Radiation Therapy Oncology Group

ClinicalTrials.gov Identifier: NCT00365105

Opioid titration order sheet or standard care in treating patients with cancer pain

Sponsor: Vanderbilt-Ingram Cancer Center

ClinicalTrials.gov Identifier: NCT00666211

This phase III study is comparing the use of an opioid titration order sheet versus standard care for the management of cancer pain. An opioid titration order sheet allows healthcare providers to adjust the dosage and schedule of pain medication. The primary outcome measure is pain, including intensity, duration, and pain-related distress. Secondary outcome measures are function, mood, and quality of life. All participants have cancer-related pain and have received at least 1 week of fixed-dose opioid therapy and satisfy any of the following criteria: self-reported inadequate pain control; the need for two or more rescue doses per day; or the need for adjustments in their pain regimen involving either fixed or breakthrough dosing.

American ginseng for cancerrelated fatigue

This phase III study intends to determine whether the perennial American ginseng (also known as Panax quinquefolius) improves cancer-related fatigue. Subjects had been diagnosed with cancer within the past 2 years and had a history of cancer-related fatigue as defined by an average score of ≥ 4 over the past 30 days on the numeric analogue scale (1-10). Patients are stratified according to baseline fatigue score, disease status of current cancer, current treatment, duration of all prior cancer treatment in their lifetime, and current tumor type, after which they are randomized to receive oral American ginseng or placebo twice daily for 14 days. Treatment is repeated every 2 weeks for a total of 4 courses. The primary outcome measure is the duration of response as measured by the general subscale Multidimensional Fatigue Symptom Inventory— Short Form (MFSI-SF).

Sponsor: North Central Cancer Treatment Group

ClinicalTrials.gov Identifier: NCT00719563

Adding custirsen for pain relief in advanced prostate cancer

This phase III study is assessing the pain palliation benefit of adding the clusterin inhibitor custirsen to docetaxel retreatment or cabazitaxel as second-line chemotherapy in men with metastatic castration-resistant prostate cancer. Selection of the chemotherapy is to be determined by the treating physician based on the patient’s first-line response. The study’s main objective is to assess pain and analgesic use for the evaluation of durable pain palliation in response to the study treatment. Pain and analgesic use are determined via a third-party contact center. Secondary outcome measures include time to pain progression and safety. An estimated 292 patients will be recruited for the study.

Sponsor: OncoGenex Technologies and Teva Pharmaceuticals USA

ClinicalTrials.gov Identifier: NCT01083615