Leuprolide Acetate or Goserelin Acetate With or Without Vismodegib Followed by Surgery in Treating Patients With Locally Advanced Prostate Cancer
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
9 other identifiers
interventional
10
1 country
5
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Jul 2010
5 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 9, 2010
CompletedFirst Submitted
Initial submission to the registry
July 14, 2010
CompletedFirst Posted
Study publicly available on registry
July 15, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2012
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2012
CompletedResults Posted
Study results publicly available
February 28, 2019
CompletedFebruary 28, 2019
February 1, 2019
1.9 years
July 14, 2010
September 10, 2018
February 6, 2019
Conditions
Outcome Measures
Primary Outcomes (1)
Proportion of Patients With =< 5% Tumor Involvement
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 Outcomes (7)
Differences in Relapse Rates by PSA Levels (Biochemical)
Date of surgery, then every 6 months, up to 8 years
Time to PSA (Biochemical) Progression, Defined as PSA Recurrence
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
From the date of surgery and elevated post operative PSA concentration, assessed up to 8 years
- +4 more other outcomes
Study Arms (2)
Arm I (leuprolide acetate, goserelin acetate, vismodegib)
EXPERIMENTALPatients 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.
Arm II (leuprolide acetate, goserelin acetate)
ACTIVE COMPARATORPatients 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.
Interventions
Given SC
Correlative studies
Given IM
Given PO
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (5)
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
Related Publications (1)
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.
PMID: 20818327DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Logothetis, Christopher, M.D. / Genitourinary Medical Oncology
- Organization
- UT MD Anderson Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Christopher Logothetis
M.D. Anderson Cancer Center
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 14, 2010
First Posted
July 15, 2010
Study Start
July 9, 2010
Primary Completion
June 1, 2012
Study Completion
June 1, 2012
Last Updated
February 28, 2019
Results First Posted
February 28, 2019
Record last verified: 2019-02