Clinical trial NCT01200810
Conditions: Adenocarcinoma of the Prostate Recurrent Prostate Cancer Stage IV Prostate Cancer
Sponsor: National Cancer Institute (NCI)
Start date: 2010-08-01; Completion date: 2012-11-01
Enrollment: 10 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This partially randomized phase II trial is studying how well giving bicalutamide together with RO4929097 works in treating patients with previously treated prostate cancer. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as bicalutamide, may lessen the amount of androgens made by the body. RO4929097 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving bicalutamide together with RO4929097 may be an effective treatment for prostate cancer

Detailed description:
PRIMARY OBJECTIVES:

I. To determine the difference in the time to PSA progression in patients with adenocarcinoma of the prostate who have rising PSA after definitive local therapy treated with bicalutamide with vs without gamma-secretase/Notch signalling pathway inhibitor RO4929097 (RO4929097).

SECONDARY OBJECTIVES:

I. To determine the proportion of patients from each arm who achieve complete response (by PSA) during the combination phase.

II. To determine the proportion of patients from each arm with PSA progression during the combination phase.

III. To determine the time to PSA nadir during the combination phase for patients in each arm.

IV. To determine the time to PSA progression during the combination phase for patients in each arm.

V. To determine the time to PSA progression during the observation phase. VI. To determine the proportion of patients with PSA progression during the observation phase.

VII. To assess the safety and tolerability of gamma-secretase inhibitor RO4929097 in combination with bicalutamide.

VIII. To evaluate expression for targets of gamma secretase inhibitor in a prostate tissue microarray.

IX. To collect serum for future evaluation of soluble markers of gamma-secretase inhibition and angiogenesis.

OUTLINE: This is a multicenter study.

INDUCTION PHASE: All patients receive induction therapy comprising oral bicalutamide once daily for at least 16 weeks. Patients whose PSA declines at least 50% continue to the randomization phase.

RANDOMIZATION PHASE: Patients are stratified according to prior therapy (radiotherapy vs surgery) and randomized to 1 of 2 treatment arms.

ARM I: Patients receive oral placebo once daily on days 1-3, 8-10, and 15-17. Treatment repeats every 21 days for 18 courses in the absence of PSA progression.

ARM II: Patients receive oral gamma-secretase/Notch signalling pathway inhibitor RO4929097 (RO4929097) once daily on days 1-3, 8-10, and 15-17. Treatment repeats every 21 days for 18 courses in the absence of PSA progression.

Patients with no disease progression continue to the combination phase. Patients with disease progression undergo imaging studies to verify the absence of metastatic disease before continuing to the combination phase.

COMBINATION PHASE: All patients then receive oral bicalutamide once daily on days 1-21 and oral RO4929097 once daily on days 1-3, 8-10, and 15-17. Courses repeat every 21 days for 12 months in the absence of disease progression or unacceptable toxicity.

Blood and tumor tissue samples may be collected periodically for correlative studies. After completion of study treatment, patients are followed up every 6 weeks for 12 months.

Arms: arm 1: Patients receive oral placebo once daily on days 1-3, 8-10, and 15-17. Treatment repeats every 21 days for 18 courses in the absence of PSA progression.

COMBINATION PHASE: All patients then receive oral bicalutamide once daily on days 1-21 and oral RO4929097 once daily on days 1-3, 8-10, and 15-17. Courses repeat every 21 days for 12 months in the absence of disease progression or unacceptable toxicity. arm 2: Patients receive oral RO4929097 once daily on days 1-3, 8-10, and 15-17. Treatment repeats every 21 days for 18 courses in the absence of PSA progression.

COMBINATION PHASE: All patients then receive oral bicalutamide once daily on days 1-21 and oral RO4929097 once daily on days 1-3, 8-10, and 15-17. Courses repeat every 21 days for 12 months in the absence of disease progression or unacceptable toxicity.
Interventions: intervention 1: placebo intervention 2: gamma-secretase/Notch signalling pathway inhibitor RO4929097 intervention 3: bicalutamide
Intervention descriptions: intervention 1: Given orally intervention 2: Given orally intervention 3: Given orally

Protocol documents: