A Pre-surgical Study of LDE225 in Men With High-risk Localized Prostate Cancer

NCT02111187 | Completed Phase 1 Results DMC

• 2 other identifiers: J1402NA_00091602
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

This trial is designed as a randomized two-arm (LDE225 vs. observation groups) open-label prospective clinical trial in men with localized high-risk prostate cancer undergoing radical prostatectomy. The investigators propose to determine the effects of LDE225 on neoplastic prostate tissue from men at high risk of systemic disease progression, by comparing pre-surgical core-biopsy specimens to tumor tissue harvested at the time of prostatectomy.

Conditions

Prostate Cancer

Keywords

LDE225; High risk localized prostate cancer; Pre-surgical

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Tissue Gli1 Expression Levels Using qRT-PCR Analysis in Each Group (LDE225 and Observation)

  This was defined as the number of patients who achieved at least a two-fold reduction in GLI1 expression in post-treatment vs. pre-treatment tumor tissues.

  Up to 3 Years

Secondary Outcomes (3)

• Percentage of Participants With a Pathological Effect of Presurgical Treatment With LDE225

  Up to 3 years

• Effect of LDE225 on PSA Recurrence Following Prostatectomy

  Up to 3 years

• Number of Participants With Adverse Events in Each Group (LDE225 and Observation)

  Up to 3 years

Study Arms (2)

LDE225 (Arm1)

ACTIVE COMPARATOR

Treatment arm (Arm 1) will receive LDE225 by mouth 800 mg daily for 4 weeks (+/- 3 days)

Drug: LDE225

Observation Arm (Arm2)

NO INTERVENTION

Observation Arm (Arm2) will receive no treatment prior to prostatectomy.

Interventions

LDE225 DRUG

Sonidegib was given as an oral drug at 800mg daily for 28 days prior to prostetoctomy

Also known as: Sonidegib

LDE225 (Arm1)

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide written informed consent prior to any screening procedures.
• Age 18 years or older.
• Histologically-documented prostatic adenocarcinoma in ≥2 cores
• ECOG performance status ≤2
• Localized prostate cancer with at least one of the following NCCN high-risk features:
• Gleason sum ≥8
• PSA \>20 ng/mL
• Clinical stage ≥T3
• Must be a candidate for radical prostatectomy
• No evidence of known metastatic disease (M0 or Mx allowed)
• Adequate bone marrow, liver and renal function as specified below:
• Absolute neutrophil count (ANC) ≥ 1500/µL
• Hemoglobin (Hgb) ≥ 9.0 g/dL
• Platelets ≥100,000/µL
• Serum total bilirubin ≤ 1.5 x ULN (upper limit of normal)

You may not qualify if:

• Patients who have had major surgery within 4 weeks of enrollment.
• Patients with concurrent uncontrolled medical conditions that may interfere with their participation in the study.
• Patients unable to take oral drugs (e.g. lack of physical integrity of the upper GI tract or known malabsorption syndromes).
• Patients who have previously been treated with LDE225 or other Hh pathway inhibitors
• Patients who have neuromuscular or muscular disorders (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy) or are on concomitant treatment with drugs that are known to cause rhabdomyolysis (such as statins and fibrates), and that cannot be discontinued at least 2 weeks prior to starting LDE225. If it is essential that the patient stays on a statin for hyperlipidemia, only pravastatin may be used with extra caution. Patients should not plan to embark on a new strenuous exercise regimen after initiation of study treatment. (NB: Muscular activities, such as strenuous exercise, that can result in significant increases in plasma CK levels should be avoided whilst on LDE225 treatment).
• Patients who have taken part in an experimental drug study within 4 weeks or 5 half-lives (whichever is longer) of initiating treatment with LDE225.
• Patients who are receiving other anti-neoplastic therapy (e.g. chemotherapy, targeted therapy or radiotherapy) concurrently or within 2 weeks of starting LDE225.
• Patients taking moderate/strong inhibitors or inducers of CYP3A4/5 or drugs metabolized by CYP2B6 or CYP2C9 that have narrow therapeutic index, and that cannot be discontinued before starting treatment with LDE225. Medications that are strong CYP3A4/5 inhibitors should be discontinued for at least 7 days and strong CYP3A/5 inducers for at least 2 weeks prior to starting treatment with LDE225.
• No concurrent use of statins (except for pravastatin, if absolutely necessary)
• No concurrent warfarin or Coumadin-derivatives
• Impaired cardiac function or significant heart disease, including any one of the following:
• Angina pectoris within 3 months
• Acute myocardial infarction within 3 months
• QTc \>450 msec on the screening ECG
• A past medical history of clinically significant ECG abnormalities or a family history of prolonged QT-interval syndrome

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead

Study Sites (1)

Johns Hopkins Hospital

Baltimore, Maryland, 21205, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

sonidegib

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Emmanuel Antonarakis
• Organization: Associate professor of oncology and urology

eantona1@jhmi.edu

443-287-0553

Study Officials

• Emmanuel Antonarakis, M.D.

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2014
• First Posted: April 11, 2014
• Study Start: April 1, 2014
• Primary Completion: January 18, 2017
• Study Completion: January 18, 2017
• Last Updated: March 7, 2019
• Results First Posted: March 7, 2019

Record last verified: 2018-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)