Overview

This trial is active, not recruiting.

Conditions prostate adenocarcinoma, stage iia prostate cancer, stage iib prostate cancer
Treatments goserelin acetate, laboratory biomarker analysis, leuprolide acetate, vismodegib
Phase phase 1/phase 2
Target PTCH1
Sponsor National Cancer Institute (NCI)
Start date July 2010
End date January 2020
Trial size 66 participants
Trial identifier NCT01163084, 2009-0473, 8384, CDR0000670590, N01CM00039, N01CM62202, NCI-2010-01737, P30CA016672, U01CA062461, U01CA062491

Summary

This randomized phase I/II trial studies giving leuprolide acetate or goserelin acetate together with or without vismodegib followed by surgery to see how well they work in treating patients with prostate cancer that has spread from where it started to nearby tissue or lymph nodes. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as leuprolide acetate or goserelin acetate, may lessen the amount of androgens made by the body. Vismodegib may slow the growth of tumor cells. Giving antihormone therapy together with vismodegib may be an effective treatment for prostate cancer.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Patients receive LHRH analogue comprising leuprolide acetate IM or goserelin acetate SC on day 1 and vismodegib PO QD on days 1-28. Treatment repeats every 28 days for up to 16 weeks in the absence of disease progression or unacceptable toxicity.
goserelin acetate ZDX
Given SC
laboratory biomarker analysis
Correlative studies
leuprolide acetate A-43818
Given IM
vismodegib Erivedge
Given PO
(Active Comparator)
Patients receive LHRH analogue comprising leuprolide acetate or goserelin acetate as in Arm I. Treatment repeats every 28 days for up to 16 weeks in the absence of disease progression or unacceptable toxicity.
goserelin acetate ZDX
Given SC
leuprolide acetate A-43818
Given IM

Primary Outcomes

Measure
Proportion of patients with =< 5% tumor involvement
time frame: Up to 8 years

Secondary Outcomes

Measure
Differences in relapse rates by bone scan/computed tomography scan (objective)
time frame: Baseline to up to 8 years
Differences in relapse rates by PSA levels (biochemical)
time frame: Baseline to up to 8 years
Differences in the rate of positive surgical margins between the two groups
time frame: Baseline to up to 8 years
Proportion of patients expressing differences in hedgehog, androgen signaling and related genes markers
time frame: Up to 8 years
Proportion of patients with PSA =< 0.2 ng/mL
time frame: Up to 8 years
Time to PSA (biochemical) progression, defined as PSA recurrence
time frame: From the date of surgery and elevated post operative PSA concentration, assessed up to 8 years
Time to PSA (clinical) progression, defined as a serial rise in PSA concentration in the presence of castrate serum testosterone concentration or radiographic evidence of progression
time frame: From the date of surgery and elevated post operative PSA concentration, assessed up to 8 years

Eligibility Criteria

Male participants at least 18 years old.

Inclusion Criteria: - Patients must have histologic proof of prostatic adenocarcinoma via a minimum of 6 core biopsy samples - Clinical stage T1c or T2 with high-grade disease (Gleason's 8-10) on initial biopsy and prostate specific antigen (PSA) > 10 ng/ml, or clinical stage T2b-T2c with Gleason's grade >= 7 - No evidence of metastatic disease as determined by imaging - Initial therapy with antiandrogen treatment is allowed but must be within 4 weeks prior to study enrollment - Appropriate surgical candidate for radical prostatectomy and an Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%) - Absence of major co-morbidity as determined by the treating physician - Leukocytes >= 3,000/mcL - Absolute neutrophil count >= 1,500/mcL - Platelets >=100,000/mcL - Total bilirubin within normal institutional limits - Aspartate aminotransferase (AST/serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT/serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal - Creatinine within normal institutional limits OR creatinine clearance >= 50 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal - Patients must have prothrombin time (PT), partial thromboplastin time (PTT) and fibrinogen levels within institutional normal limits and no history of substantial non-iatrogenic bleeding diathesis - Men and their female partners must agree to use two forms of contraception (i.e., barrier contraception and one other method of contraception) during study treatment and for at least 12 months post-treatment - Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: - Histologic variants in the primary tumor (histologic variants other than adenocarcinoma) - Patients who have had chemotherapy or radiotherapy for prostate cancer prior to entering the study - Patients who have received prior treatment with GDC-0449 - Patients may not be receiving any other investigational agents - Patients receiving previous androgen ablation or current androgen ablation of greater than 4 week's duration - Patients who are not appropriate surgical candidates for radical prostatectomy based on the evaluation of co-existent medical diseases and competing causes of death (such as but not limited to, unstable angina, myocardial infarction within the previous 6 months, or use of ongoing maintenance therapy for life-threatening ventricular arrhythmia, uncontrolled hypertension) - History of allergic reactions attributed to compounds of similar chemical or biologic composition to GDC-0449 or LHRH analogues - Patients taking medications with narrow therapeutic indices that are metabolized by cytochrome P450 (CYP450), including warfarin sodium (Coumadin®) are ineligible - Patients with malabsorption syndrome or other condition that would interfere with intestinal absorption; patients must be able to swallow capsules - Patients with clinically important (in the opinion of the treating physician) history of liver disease, including viral or other hepatitis or cirrhosis are ineligible - Patients with uncontrolled hypocalcemia, hypomagnesemia, hyponatremia or hypokalemia defined as less than the lower limit of normal for the institution, despite adequate electrolyte supplementation are excluded from this study - Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements - Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible - Patients with prior malignancy if there is an increased chance (>= 30%) of relapse in the following five years (in the opinion of the treating physician) - Patients who have received systemic treatment for cancer within the last 6 months

Additional Information

Official title A Randomized Phase Ib/II Study of Preoperative GDC-0449 and Androgen Ablation Compared to Androgen Ablation Alone Followed by Radical Prostatectomy for Select Patients With Locally Advanced Adenocarcinoma of the Prostate
Principal investigator Christopher Logothetis
Description PRIMARY OBJECTIVES: I. To assess the difference in less than or equal to 5% tumor involvement between patients between the two arms. SECONDARY OBJECTIVES: I. To assess differences in hedgehog signaling, androgen signaling, markers linked to high grade prostate cancer (PCa) progression, proliferation, apoptosis, and the expression of androgen producing enzymes in the tumor microenvironment between the two arms. II. To assess safety of preoperative GDC-0449 (vismodegib) in combination with luteinizing hormone-releasing hormone (LHRH). III. To assess the difference in proportion of patients with negative disease surgical margins between the two arms. IV. To collect and archive tissue from the primary tumor, bone marrow and blood (serum, plasma), bone marrow aspirate for future study. V. To assess difference in relapse rate (biochemical, objective) and time to progression. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I (androgen-ablation therapy and vismodegib): Patients receive LHRH analogue comprising leuprolide acetate intramuscularly (IM) or goserelin acetate subcutaneously (SC) on day 1 and vismodegib orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 16 weeks in the absence of disease progression or unacceptable toxicity. ARM II (androgen-ablation therapy): Patients receive LHRH analogue comprising leuprolide acetate or goserelin acetate as in Arm I. Treatment repeats every 28 days for up to 16 weeks in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients undergo radical prostatectomy. After completion of study therapy, patients are followed up every 6 months for up to 8 years.
Trial information was received from ClinicalTrials.gov and was last updated in July 2016.
Information provided to ClinicalTrials.gov by National Cancer Institute (NCI).