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

February 6, 2019 updated by: National Cancer Institute (NCI)

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
10

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Comprehensive Cancer Center
      • Detroit, Michigan, United States, 48201
        • Wayne State University/Karmanos Cancer Institute
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
    • Texas
      • Houston, Texas, United States, 77030
        • M D Anderson Cancer Center
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin Hospital and Clinics

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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.
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Vismodegib
Given PO
Other Names:
  • Erivedge
  • GDC-0449
  • Hedgehog Antagonist GDC-0449
Drug: Goserelin Acetate
Given SC
Other Names:
  • ZDX
  • Zoladex
Drug: Leuprolide Acetate
Given IM
Other Names:
  • Enantone
  • LEUP
  • Lupron
  • Lupron Depot
  • Leuprorelin Acetate
  • A-43818
  • Abbott 43818
  • Abbott-43818
  • Carcinil
  • Depo-Eligard
  • Eligard
  • Enanton
  • Enantone-Gyn
  • Ginecrin
  • Leuplin
  • Lucrin
  • Lucrin Depot
  • Lupron Depot-3 Month
  • Lupron Depot-4 Month
  • Lupron Depot-Ped
  • Procren
  • Procrin
  • Prostap
  • TAP-144
  • Trenantone
  • Uno-Enantone
  • Viadur
Active Comparator: 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.
Drug: Goserelin Acetate
Given SC
Other Names:
  • ZDX
  • Zoladex
Drug: Leuprolide Acetate
Given IM
Other Names:
  • Enantone
  • LEUP
  • Lupron
  • Lupron Depot
  • Leuprorelin Acetate
  • A-43818
  • Abbott 43818
  • Abbott-43818
  • Carcinil
  • Depo-Eligard
  • Eligard
  • Enanton
  • Enantone-Gyn
  • Ginecrin
  • Leuplin
  • Lucrin
  • Lucrin Depot
  • Lupron Depot-3 Month
  • Lupron Depot-4 Month
  • Lupron Depot-Ped
  • Procren
  • Procrin
  • Prostap
  • TAP-144
  • Trenantone
  • Uno-Enantone
  • Viadur

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Proportion of Patients With =< 5% Tumor Involvement
Time Frame: Baseline up to 4 months or radical prostatectomy, whichever comes first
Each patient's pathologic staging will be assessed from the samples collected from prostatectomy. Will be descriptively summarized. Two-sided Chi-Square test will be used to provide the test of significance between the 2 groups of LHRHa versus LHRHa plus vismodegib.
Baseline up to 4 months or radical prostatectomy, whichever comes first

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Differences in Relapse Rates by PSA Levels (Biochemical)
Time Frame: Date of surgery, then every 6 months, up to 8 years
Will be descriptively summarized.
Date of surgery, then every 6 months, 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
Will be descriptively summarized. PSA recurrence is defined as two (2) serial measureable rises in PSA concentration above the undetectable level with the standard assay (> 0.1 ng/mL).
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
Will be descriptively summarized. PSA recurrence is defined as two (2) serial measureable rises in PSA concentration above the undetectable level with the standard assay (> 0.1 ng/mL).
From the date of surgery and elevated post operative PSA concentration, assessed up to 8 years
Proportion of Patients With PSA =< 0.2 ng/mL
Time Frame: Up to 8 years
Will be descriptively summarized.
Up to 8 years
Differences in the Rate of Positive Surgical Margins Between the Two Groups
Time Frame: Baseline to up to 8 years
Will be descriptively summarized.
Baseline to up to 8 years
Differences in Relapse Rates by Bone Scan/Computed Tomography Scan (Objective)
Time Frame: Baseline to up to 8 years
Will be descriptively summarized.
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
Up to 8 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
National Cancer Institute (NCI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Christopher Logothetis, M.D. Anderson Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 9, 2010

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2012

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2012

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 14, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 14, 2010

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 15, 2010

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 28, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 6, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NCI-2010-01737 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • P30CA016672 (U.S. NIH Grant/Contract)
  • N01CM62202 (U.S. NIH Grant/Contract)
  • U01CA062491 (U.S. NIH Grant/Contract)
  • N01CM00039 (U.S. NIH Grant/Contract)
  • U01CA062461 (U.S. NIH Grant/Contract)
  • 2009-0473 (M D Anderson Cancer Center)
  • CDR0000670590
  • 8384 (Other Identifier: CTEP)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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