Prostate CancerPhase 1LDE225NCT02111187
A Pre-surgical Study of LDE225 in Men With High-risk Localized Prostate Cancer
A Phase 1 study testing LDE225 in people with Prostate Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 100 years, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- LDE225
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2014to 18 Jan 2017
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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)
- AST and ALT ≤ 2.5 x ULN
- Plasma creatine phosphokinase (CK) < 1.5 x ULN, if known
- Serum creatinine ≤ 1.5 x ULN [or 24-hour creatinine clearance ≥ 50ml/min]
- Patient is able to swallow and retain oral medications
Who cannot join
- 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.
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- 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
- Other clinically significant heart disease (e.g. heart failure, uncontrolled/labile hypertension, or history of poor compliance with an antihypertensive regimen)
- Patients who are not willing to apply highly effective contraception during the study and through the duration of LDE225 treatment.
- Male patients must use highly effective (double barrier) methods of contraception (e.g., spermicidal gel plus condom) for the entire duration of the study, and continuing using contraception and refrain from fathering a child for 6 months following the last dose of the study drug. A condom is also required to be used by vasectomized men as well as during intercourse with a male partner in order to prevent delivery of the study treatment via seminal fluid. Sexually active males must be willing to use a condom during intercourse while taking the study drug and for 6 months after stopping investigational medications and agree not to father a child during this period.
- Patients unwilling or unable to comply with the research protocol.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Pharmacodynamic Pre-surgical Study of Hedgehog Pathway Inhibition With LDE225 in Men With High-risk Localized Prostate Cancer.
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.
Read the detailed description
High-risk patients will be identified based on their core-needle biopsy features, PSA levels, and clinical stage. After obtaining baseline laboratory and clinical values (including an ECG, PSA, hematologic, and renal and hepatic panels), men will receive oral LDE225 800 mg/day or observation daily for 4 weeks (±3 days) prior to prostatectomy. Patients will have a clinical visit and an ECG and laboratory testing will be performed at 2 weeks and then again at 4 weeks, including a 4-week pre-prostatectomy measurement of PSA and a blood sample to determine plasma LDE225 levels. Men will undergo radical prostatectomy (with bilateral pelvic lymphadenectomy as appropriate), at which point two 250-mg biopsies of prostate tissue will be obtained, frozen and stored for analysis.
- Conditions
- Prostate Cancer
- Being tested
- LDE225
- Keywords
- LDE225, High risk localized prostate cancer, Pre-surgical
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LDE225Drug
Also called Sonidegib
Sonidegib was given as an oral drug at 800mg daily for 28 days prior to prostetoctomy
| Study group | Role | What they receive |
|---|---|---|
| LDE225 (Arm1) | Active comparator | Treatment arm (Arm 1) will receive LDE225 by mouth 800 mg daily for 4 weeks (+/- 3 days) Receives: Drug: LDE225 |
| Observation Arm (Arm2) | No intervention | Observation Arm (Arm2) will receive no treatment prior to prostatectomy. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 3 Years
Secondary outcomes (3)
Percentage of Participants With a Pathological Effect of Presurgical Treatment With LDE225
To determine whether presurgical treatment with LDE225 can exert a pathological effect on high-risk tumors (i.e. increase apoptosis, decrease proliferation).
Measured: Up to 3 years
Effect of LDE225 on PSA Recurrence Following Prostatectomy
To evaluate whether presurgical treatment with LDE225 diminishes the risk of PSA recurrence following prostatectomy.
Measured: Up to 3 years
Number of Participants With Adverse Events in Each Group (LDE225 and Observation)
Safety and tolerability, including any drug-related toxicities of Sonidegib, were reported via CTCAE version 4.0.
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2014 (estimated)
- Study startApr 2014
- Primary completion18 Jan 2017
- Study completion18 Jan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Emmanuel Antonarakis, M.D., Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02111187
- Sponsor's protocol ID
- J1402
- Other IDs
- NA_00091602
- Acronym
- LDE225
- Status last verified
- Nov 2018
- First submitted
- 1 Apr 2014
- Last updated
- 7 Mar 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pharmacodynamic Pre-surgical Study of Hedgehog Pathway Inhibition With LDE225 in Men With High-risk Localized Prostate Cancer.
- ClinicalTrials.gov ID
- NCT02111187
- Acronym / sponsor ID
- LDE225 / J1402
- Conditions
- Prostate Cancer
- Keywords
- LDE225, High risk localized prostate cancer, Pre-surgical
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Study start
- Apr 2014 (actual)
- Primary completion
- 18 Jan 2017 (actual)
- Study completion
- 18 Jan 2017 (actual)
- First posted
- 11 Apr 2014 (estimated)
- Results
- Posted 7 Mar 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
High-risk patients will be identified based on their core-needle biopsy features, PSA levels, and clinical stage. After obtaining baseline laboratory and clinical values (including an ECG, PSA, hematologic, and renal and hepatic panels), men will receive oral LDE225 800 mg/day or observation daily for 4 weeks (±3 days) prior to prostatectomy. Patients will have a clinical visit and an ECG and laboratory testing will be performed at 2 weeks and then again at 4 weeks, including a 4-week pre-prostatectomy measurement of PSA and a blood sample to determine plasma LDE225 levels. Men will undergo radical prostatectomy (with bilateral pelvic lymphadenectomy as appropriate), at which point two 250-mg biopsies of prostate tissue will be obtained, frozen and stored for analysis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LDE225 (Arm1) | Active comparator | Drug: LDE225Treatment arm (Arm 1) will receive LDE225 by mouth 800 mg daily for 4 weeks (+/- 3 days) |
| Observation Arm (Arm2) | No intervention | –Observation Arm (Arm2) will receive no treatment prior to prostatectomy. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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:
Key exclusion criteria (19 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LDE225Also: SonidegibSonidegib was given as an oral drug at 800mg daily for 28 days prior to prostetoctomy | Drug | LDE225 (Arm1) |
Primary outcome
Change From Baseline in Tissue Gli1 Expression Levels Using qRT-PCR Analysis in Each Group (LDE225 and Observation)
Time frame: Up to 3 Years
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.
3 secondary outcomes
Percentage of Participants With a Pathological Effect of Presurgical Treatment With LDE225
Time frame: Up to 3 years
Effect of LDE225 on PSA Recurrence Following Prostatectomy
Time frame: Up to 3 years
Number of Participants With Adverse Events in Each Group (LDE225 and Observation)
Time frame: Up to 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Emmanuel Antonarakis, M.D. principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing LDE225 in people with Prostate Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Mar 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Tissue Gli1 Expression Levels Using qRT-PCR Analysis in Each Group (LDE225 and Observation) (time frame: Up to 3 Years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Mar 2019.