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

Prostate Adenocarcinoma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01163084
• Other study ID #: NCI-2010-01737
• Secondary ID: NCI-2010-01737CD
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: July 9, 2010
• Est. completion date: June 1, 2012

Study information

• Verified date: February 2019
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. completion date: June 1, 2012
• Est. primary completion date: June 1, 2012
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Prostate Adenocarcinoma
• Prostatic Neoplasms
• Stage IIA Prostate Cancer AJCC v7
• Stage IIB Prostate Cancer AJCC v7

Intervention

Drug:
• Goserelin Acetate
Given SC

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Leuprolide Acetate
Given IM
• Vismodegib
Given PO

Locations

Country	Name	City	State
United States	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

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Differences in Relapse Rates by PSA Levels (Biochemical)	Will be descriptively summarized.	Date of surgery, then every 6 months, up to 8 years
Other	Time to PSA (Biochemical) Progression, Defined as PSA Recurrence	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
Other	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	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
Other	Proportion of Patients With PSA =< 0.2 ng/mL	Will be descriptively summarized.	Up to 8 years
Other	Differences in the Rate of Positive Surgical Margins Between the Two Groups	Will be descriptively summarized.	Baseline to up to 8 years
Other	Differences in Relapse Rates by Bone Scan/Computed Tomography Scan (Objective)	Will be descriptively summarized.	Baseline to up to 8 years
Other	Proportion of Patients Expressing Differences in Hedgehog, Androgen Signaling and Related Genes Markers		Up to 8 years
Primary	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