Clinical Trials in Progress for Urologic Cancers

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 will present summaries of ongoing research relating to a variety of urologic cancers.

Bladder Cancer

Intravesical EN3348 vs mitomycin C for bladder cancer

This phase III study will compare EN3348 (Mycobacterial Cell Wall-DNA Complex [MCC]) with mitomycin C in the intravesical treatment of patients with bacillus Calmette-Guérin (BCG)-recurrent or -refractory nonmuscle invasive bladder cancer (Ta high grade, T1 low or high grade, or carcinoma in situ). Refractory disease in the roughly 450-patient study is defined as evidence of persistent high-grade bladder cancer (Ta HG, T1, and/or CIS) at least 6 months from the start of a full induction course of BCG with or without maintenance/retreatment at 3 months. Recurrent disease is defined as the reappearance of disease after achieving a tumor-free status by 6 months following a full induction course of BCG with or without maintenance/retreatment at 3 months; subjects with recurrent disease must have had their recurrence within 18 months following the last dose of BCG. The primary outcome measure is efficacy. About 450 patients will participate at 77 sites.

Sponsor: Endo Pharmaceuticals

ClinicalTrials.gov Identifier: NCT01200992

Prostate Cancer

Zoledronate for bone loss prevention in prostate cancer

This phase III trial study will compare the effectiveness of the bisphosphonate zoledronate combined with calcium versus calcium alone for preventing bone loss in men with stage III or IV prostate cancer who have received long-term androgen-deprivation therapy. Patients randomized to the experimental arm receive zoledronate administered intravenously over 15 minutes on day 1 and oral calcium gluconate and oral cholecalciferol daily, with the regimen repeated every 3 months for 12 months in the absence of toxicity. Patients assigned to the active comparator arm receive oral calcium gluconate and oral cholecalciferol without zoledronate. The primary outcome measure is bone density change as measured by dual-energy x-ray absorptiometry from baseline to 13 months. The researchers will also determine the percentage change in lumbar spine and hip bone density as measured by plain film x-rays of lumbar spine and pelvis and assess markers of bone formation and resorption, the incidence of skeletal events, and the incidence of new or progressive bone metastatic disease.

Sponsor: Northwestern University

ClinicalTrials.gov Identifier: NCT00058188

Tadalafil for preventing post-radiotherapy erectile dysfunction in prostate cancer

This phase III study is testing the effectiveness of the phosphodiesterase 5 inhibitor tadalafil for preventing erectile dysfunction in men treated with radiotherapy for prostate cancer. Patients are stratified according to age (≤ 65 years vs > 65 years) and radiotherapy treatment (external-beam radiotherapy alone to the prostate ± seminal vesicles only at a dose of 75-79.2 Gy or brachytherapy alone). Afterwards, they are randomized to receive oral tadalafil or placebo once daily for 24 weeks in the absence of disease progression or unacceptable toxicity. The primary outcome measure is spontaneous (off-drug) erectile function as measured by the International Index of Erectile Function at weeks 28-30. The estimated primary completion date is April 2013.

Sponsor: Radiation Therapy Oncology Group

ClinicalTrials.gov Identifier: NCT00931528

Prechemotherapy tasquinimod for advanced prostate cancer

This phase III study will compare tasquinimod versus placebo in men with asymptomatic to mildly symptomatic metastatic castration-resistant prostate cancer prior to chemotherapy. Tasquinimod is a second-generation oral quinoline-3-carboxamide analogue. Approximately 1200 patients will be randomly assigned in a 2:1 ratio to treatment with tasquinimod 0.25, 0.5, or 1 mg daily, or placebo. The primary outcome measure is progression-free survival. Investigators at 219 sites are participating and hope to complete the study by January 2016. In order to be eligible, patients must have evidence of bone metastatic disease on radiographic examination and evidence of progressive disease after castration levels of testosterone have been achieved, and a Karnofsky score ≥70%.

Sponsor: Active Biotech AB

ClinicalTrials.gov Identifier: NCT01234311

Recombinant vaccine for metastatic prostate cancer

This phase III study will compare the use of the viral-based anti-prostate-specific antigen vaccine PROSTVAC alone or in combination with GM-CSF in men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer. The primary outcome measure is overall survival, which will be determined in two separate comparisons: PROSTVAC plus adjuvant-dose GM-CSF versus controls, and PROSTVAC without GM-CSF versus controls. As a secondary endpoint, the investigators will determine the percentage of patients receiving PROSTVAC with or without GM-CSF who remain event-free (defined as an absence of radiological progression, pain progression, initiation of chemotherapy, or death) at 6 months compared with placebo. The study has an estimated enrollment of 1200 patients, with an estimated completion date of August 2015.

Sponsor: BN ImmunoTherapeutics

ClinicalTrials.gov Identifier: NCT01322490

Renal Cancer

Adjuvant pazopanib under study for localized renal cancer

This phase III study will compare the multitargeted tyrosine kinase inhibitor pazopanib versus placebo as adjuvant therapy in patients with localized or locally advanced renal cell carcinoma following nephrectomy. Patients will be randomized to 12 months’ daily treatment with oral pazopanib 800 mg daily or placebo. The pazopanib or placebo dose can be reduced or treatment interrupted or stopped due to adverse events or intolerance. The primary outcome measure is disease-free survival. Secondary outcome measures are overall survival, disease-free survival rates at yearly time points, safety, and health outcome defined as the change from baseline in patients’ self-reports on health outcome and quality of life as measured by two instruments: the Functional Assessment of Cancer Therapy-Kidney Symptom Index-19 and EuroQoL-5D. Investigators at 290 sites are aiming to recruit 1500 patients.

Sponsor: GlaxoSmithKline

ClinicalTrials.gov Identifier: NCT01235962

Sorafenib in patients with resected renal cancer at risk of relapse

This phase III study will compare the multitargeted tyrosine kinase inhibitor sorafenib with placebo for treating patients with resected primary renal cell carcinoma who have an intermediate or high risk of relapse. Subjects will be randomized to one of three treatment arms: Patients in arm I will receive oral placebo twice daily for 3 years in the absence of disease progression or unacceptable toxicity; patients in arm II will receive oral sorafenib twice daily for 1 year and oral placebo twice daily for 2 years in the absence of disease progression or unacceptable toxicity; and patients in arm III will receive oral sorafenib twice daily for 3 years in the absence of disease progression or unacceptable toxicity. Patients in arms I and II with progressive disease may cross over and receive treatment in arm III. The primary outcome measure is disease-free survival. Secondary outcome measures are metastasis-free survival, disease-specific survival time, overall survival, cost-effectiveness, and toxicity. The investigators intend to recruit 1656 patients.

Sponsor: Medical Research Council

ClinicalTrials.gov Identifier: NCT00492258

Bevacizumab plus temsirolimus or interferon-alfa in advanced renal cancer

This phase IIIb study will compare bevacizumab plus temsirolimus versus bevacizumab plus interferon-alfa as first-line treatment in patients with advanced renal cell carcinoma. Subjects are required to have histologically and/or cytologically confirmed advanced renal cell carcinoma with a majority component of conventional clear-cell type, plus at least one measurable lesion per Response Evaluation Criteria In Solid Tumors (RECIST).

About 791 patients will be randomized to bevacizumab IV 10 mg/kg every 8 weeks plus either temsirolimus 25 mg IV weekly or interferon-alfa 9MU given subcutaneously every 3 weeks. The primary outcome measure is independently assessed progression-free survival (PFS). Secondary outcome measures are safety, investigator-assessed PFS, objective response rate, and survival.

Sponsor: Pfizer

ClinicalTrials.gov Identifier: NCT00631371