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Trial · Interventional

TerminatedPhase 1/2Results postedRegistry data

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

NCTNCT01163084 (opens ClinicalTrials.gov in a new tab)Other idNCI-2010-01737Other idNCI-2010-01737Other idCDR0000670590Other id2009-0473

Overview

Status
Terminated
Phase
Phase 1/2
Enrollment
10 participants (actual)
Sponsor
National Cancer Institute (NCI) · Nih
Design
Randomized · Open label (no masking)
Countries
1 country

United States

Start
9 Jul 2010
Primary completion
1 Jun 2012
Completion
1 Jun 2012
First posted
15 Jul 2010 (estimated)
Last update posted
28 Feb 2019
Conditions
Prostate Adenocarcinoma · Stage IIA Prostate Cancer AJCC v7 · Stage IIB Prostate Cancer AJCC v7

Timeline

1 trial · 1 stopped early · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2010201120122013
  1. Ph 1/2

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

    NCT01163084

    9 Jul 2010 to 1 Jun 2012

    Terminated

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

  • Goserelin AcetateDrug
  • Laboratory Biomarker AnalysisOther
  • Leuprolide AcetateDrug
  • VismodegibDrug

Arms2

  • 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.

  • 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.

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Proportion of Patients With =< 5% Tumor Involvement

    Time frame · Baseline up to 4 months or radical prostatectomy, whichever comes first

    Registry description

    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.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcome· Baseline up to 4 months or radical prostatectomy, whichever comes first

Proportion of Patients With =< 5% Tumor Involvement

GroupValue
Group A-GDC-0449 and Androgen Ablation (LHRHanot posted
Group B Androgen Ablation (LHRHa) Alonenot posted
Secondary and other outcome results(7)
Other pre specified outcome· Date of surgery, then every 6 months, up to 8 years

Differences in Relapse Rates by PSA Levels (Biochemical)

GroupValue
Other pre specified outcome· From the date of surgery and elevated post operative PSA concentration, assessed up to 8 years

Time to PSA (Biochemical) Progression, Defined as PSA Recurrence

GroupValue
Other pre specified outcome· 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

GroupValue
Other pre specified outcome· Up to 8 years

Proportion of Patients With PSA =< 0.2 ng/mL

GroupValue
Other pre specified outcome· Baseline to up to 8 years

Differences in the Rate of Positive Surgical Margins Between the Two Groups

GroupValue
Other pre specified outcome· Baseline to up to 8 years

Differences in Relapse Rates by Bone Scan/Computed Tomography Scan (Objective)

GroupValue
Other pre specified outcome· Up to 8 years

Proportion of Patients Expressing Differences in Hedgehog, Androgen Signaling and Related Genes Markers

GroupValue

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Group A- GDC-0449 and Androgen Ablation (LHRHa)Group A will receive 150mg GDC-0449 daily for 3 months prior to radical prostatectomy.0 / 40 / 44 / 4
Group B- Androgren Ablation (LHRHa) AlonePatients will receive an LHRHa (monthly injection or three-month injection) for a maximum of 4 months before a prostatectomy is performed.0 / 50 / 55 / 5

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Other registry references

References listed at the registry that are not in PepBank. They link to PubMed.

  • DerivedKarlou 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 20818327

Eligibility

Who could join, as posted.

Sex
Male
Age
from 18 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
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

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