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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01163084
First received: July 14, 2010
Last updated: September 16, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Adenocarcinoma of the Prostate
Stage IIA Prostate Cancer
Stage IIB Prostate Cancer
Drug: leuprolide acetate
Drug: goserelin acetate
Drug: vismodegib
Other: laboratory biomarker analysis
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Proportion of patients with =< 5% tumor involvement [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Proportion of patients expressing differences in hedgehog, androgen signaling and related genes markers [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]
  • Differences in relapse rates by PSA levels (biochemical) [ Time Frame: Baseline to up to 8 years ] [ Designated as safety issue: No ]
    Will be descriptively summarized.

  • Differences in relapse rates by bone scan/computed tomography scan (objective) [ Time Frame: Baseline to up to 8 years ] [ Designated as safety issue: No ]
    Will be descriptively summarized.

  • 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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: From the date of surgery and elevated post operative PSA concentration, assessed up to 8 years ] [ Designated as safety issue: No ]
    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).

  • Differences in the rate of positive surgical margins between the two groups [ Time Frame: Baseline to up to 8 years ] [ Designated as safety issue: No ]
    Will be descriptively summarized.

  • Proportion of patients with PSA =< 0.2 ng/mL [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]
    Will be descriptively summarized.


Estimated Enrollment: 66
Study Start Date: July 2010
Estimated Primary Completion Date: May 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: leuprolide acetate
Given IM
Other Names:
  • Enantone
  • LEUP
  • Lupron
  • Lupron Depot
Drug: goserelin acetate
Given SC
Other Names:
  • ICI-118630
  • ZDX
  • Zoladex
Drug: vismodegib
Given PO
Other Names:
  • Erivedge
  • GDC-0449
  • Hedgehog antagonist GDC-0449
Other: laboratory biomarker analysis
Correlative studies
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: leuprolide acetate
Given IM
Other Names:
  • Enantone
  • LEUP
  • Lupron
  • Lupron Depot
Drug: goserelin acetate
Given SC
Other Names:
  • ICI-118630
  • ZDX
  • Zoladex

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01163084

Locations
United States, Michigan
University of Michigan University Hospital
Ann Arbor, Michigan, United States, 48109
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
Investigators
Principal Investigator: Christopher Logothetis M.D. Anderson Cancer Center
  More Information

No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01163084     History of Changes
Other Study ID Numbers: NCI-2010-01737, NCI-2010-01737, CDR0000670590, 2009-0473, 8384, N01CM62202, N01CM00039, P30CA016672, U01CA062461, U01CA062491
Study First Received: July 14, 2010
Last Updated: September 16, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Prostatic Neoplasms
Adenocarcinoma
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Leuprolide
Goserelin
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on September 22, 2014