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

NCT ID: NCT01163084

Last Updated: 2019-02-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-07-09
• Study Completion Date: 2012-06-01

Brief 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.

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.

Conditions

Prostate Adenocarcinoma; Stage IIA Prostate Cancer AJCC v7; Stage IIB Prostate Cancer AJCC v7

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I (leuprolide acetate, goserelin acetate, vismodegib)

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.

Group Type: EXPERIMENTAL

Goserelin Acetate

Intervention Type: DRUG

Given SC

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Leuprolide Acetate

Intervention Type: DRUG

Given IM

Vismodegib

Intervention Type: DRUG

Given PO

Arm II (leuprolide acetate, goserelin acetate)

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.

Group Type: ACTIVE_COMPARATOR

Goserelin Acetate

Intervention Type: DRUG

Given SC

Leuprolide Acetate

Intervention Type: DRUG

Given IM

Interventions

Goserelin Acetate

Given SC

Intervention Type: DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Leuprolide Acetate

Given IM

Intervention Type: DRUG

Vismodegib

Given PO

Intervention Type: DRUG

Other Intervention Names

ZDX; Zoladex; A-43818; Abbott 43818; Abbott-43818; Carcinil; Depo-Eligard; Eligard; Enanton; Enantone; Enantone-Gyn; Ginecrin; LEUP; Leuplin; Leuprorelin Acetate; Lucrin; Lucrin Depot; Lupron; Lupron Depot; Lupron Depot-3 Month; Lupron Depot-4 Month; Lupron Depot-Ped; Procren; Procrin; Prostap; TAP-144; Trenantone; Uno-Enantone; Viadur; Erivedge; GDC-0449; Hedgehog Antagonist GDC-0449

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christopher Logothetis

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, United States

Duke University Medical Center

Durham, North Carolina, United States

M D Anderson Cancer Center

Houston, Texas, United States

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Countries

United States

References

Karlou M, Tzelepi V, Efstathiou E. Therapeutic targeting of the prostate cancer microenvironment. Nat Rev Urol. 2010 Sep;7(9):494-509. doi: 10.1038/nrurol.2010.134.

Reference Type: DERIVED

PMID: 20818327 (View on PubMed)

Other Identifiers

NCI-2010-01737

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000670590

Identifier Type: -

Identifier Source: secondary_id

2009-0473

Identifier Type: OTHER

Identifier Source: secondary_id

8384

Identifier Type: OTHER

Identifier Source: secondary_id

N01CM00039

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01CM62202

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA016672

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01CA062461

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01CA062491

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2010-01737

Identifier Type: -

Identifier Source: org_study_id