Prostate Adenocarcinoma, Stage IIA Prostate Cancer AJCC v7, Stage IIB Prostate Cancer AJCC v7
Conditions
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.
Interventions
DRUGGoserelin Acetate
Given SC
OTHERLaboratory Biomarker Analysis
Correlative studies
DRUGLeuprolide Acetate
Given IM
DRUGVismodegib
Given PO
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients With =< 5% Tumor Involvement | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Differences in Relapse Rates by PSA Levels (Biochemical) | Date of surgery, then every 6 months, up to 8 years | Will be descriptively summarized. |
| 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 | 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). |
| 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 | 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). |
| Proportion of Patients Expressing Differences in Hedgehog, Androgen Signaling and Related Genes Markers | Up to 8 years | — |
| Differences in the Rate of Positive Surgical Margins Between the Two Groups | Baseline to up to 8 years | Will be descriptively summarized. |
| Differences in Relapse Rates by Bone Scan/Computed Tomography Scan (Objective) | Baseline to up to 8 years | Will be descriptively summarized. |
| Proportion of Patients With PSA =< 0.2 ng/mL | Up to 8 years | Will be descriptively summarized. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited by physicians in the Genitourinary Medical Oncology Clinic and Urology clinic.
Pre-assignment details
10 participants started but only 9 were randomized
Participants by arm
| Arm | Count |
|---|---|
| Group A- GDC-0449 and Androgen Ablation (LHRHa) Group A will receive 150mg GDC-0449 daily for 3 months prior to radical prostatectomy. | 4 |
| Group- B Androgren Ablation (LHRHa) Alone Patients will receive an LHRHa (monthly injection or three-month injection) for a maximum of 4 months before a prostatectomy is performed. | 5 |
| Total | 9 |
Baseline characteristics
| Characteristic | Group A- GDC-0449 and Androgen Ablation (LHRHa) | Group- B Androgren Ablation (LHRHa) Alone | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 1 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 4 Participants | 6 Participants |
| Age, Continuous | 63 years | 63 years | 63 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 1 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 3 Participants | 4 Participants | 7 Participants |
| Region of Enrollment United States | 4 participants | 5 participants | 9 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 4 Participants | 5 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 5 |
| other Total, other adverse events | 4 / 4 | 5 / 5 |
| serious Total, serious adverse events | 0 / 4 | 0 / 5 |
Outcome results
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.
Time frame: Baseline up to 4 months or radical prostatectomy, whichever comes first
Population: Results was not determined.
Other Pre-specified
Differences in Relapse Rates by Bone Scan/Computed Tomography Scan (Objective)
Will be descriptively summarized.
Time frame: Baseline to up to 8 years
Other Pre-specified
Differences in Relapse Rates by PSA Levels (Biochemical)
Will be descriptively summarized.
Time frame: Date of surgery, then every 6 months, up to 8 years
Other Pre-specified
Differences in the Rate of Positive Surgical Margins Between the Two Groups
Will be descriptively summarized.
Time frame: Baseline to up to 8 years
Other Pre-specified
Proportion of Patients Expressing Differences in Hedgehog, Androgen Signaling and Related Genes Markers
Time frame: Up to 8 years
Other Pre-specified
Proportion of Patients With PSA =< 0.2 ng/mL
Will be descriptively summarized.
Time frame: Up to 8 years
Other Pre-specified
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).
Time frame: From the date of surgery and elevated post operative PSA concentration, assessed up to 8 years
Other Pre-specified
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).
Time frame: From the date of surgery and elevated post operative PSA concentration, assessed up to 8 years