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Leuprolide Acetate or Goserelin Acetate With or Without Vismodegib Followed by Surgery in Treating Patients With Locally Advanced Prostate Cancer

Information source: National Cancer Institute (NCI)
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Prostate Adenocarcinoma; Stage IIA Prostate Cancer; Stage IIB Prostate Cancer

Intervention: Goserelin Acetate (Drug); Laboratory Biomarker Analysis (Other); Leuprolide Acetate (Drug); Vismodegib (Drug)

Phase: Phase 1/Phase 2

Status: Active, not recruiting

Sponsored by: National Cancer Institute (NCI)

Official(s) and/or principal investigator(s):
Christopher Logothetis, Principal Investigator, Affiliation: M.D. Anderson Cancer Center


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.

Clinical Details

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

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Proportion of patients with =< 5% tumor involvement

Secondary outcome:

Differences in relapse rates by bone scan/computed tomography scan (objective)

Differences in relapse rates by PSA levels (biochemical)

Differences in the rate of positive surgical margins between the two groups

Proportion of patients expressing differences in hedgehog, androgen signaling and related genes markers

Proportion of patients with PSA =< 0.2 ng/mL

Time to PSA (biochemical) progression, defined as PSA recurrence

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

Detailed 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.


Minimum age: 18 Years. Maximum age: N/A. Gender(s): Male.


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


- 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

Locations and Contacts

University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan 48109, United States

Wayne State University/Karmanos Cancer Institute, Detroit, Michigan 48201, United States

Duke University Medical Center, Durham, North Carolina 27710, United States

M D Anderson Cancer Center, Houston, Texas 77030, United States

University of Wisconsin Hospital and Clinics, Madison, Wisconsin 53792, United States

Additional Information

Starting date: July 2010
Last updated: May 6, 2015

Page last updated: August 23, 2015

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