Hepatocellular CarcinomaPhase 1NCT02151864
LDE225 in Patients With Advanced or Metastatic Hepatocellular Carcinoma and Child-Pugh A/B7 Cirrhosis
A Phase 1 study testing LDE225 in people with Hepatocellular Carcinoma and Cirrhosis, run by Jason K. Sicklick, M.D. at 1 site in United States.
Trial summary
The purpose of this study is to test the safety and determine the maximum safe dose of an experimental drug called LDE225 (hedgehog inhibitor) in people with liver cancer. We have identified hedgehog dysregulation as a novel mechanism for hepatocarcinogenesis and hepatic fibrosis/cirrhosis. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma, Cirrhosis
- 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
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2014to Sep 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 years or older
- Pathological confirmation of advanced or metastatic HCC
- HCC not amenable to surgical resection, liver transplantation, chemoembolization, or ablation therapy
- Patients with Child-Pugh A and Child-Pugh B7 (if due to low albumin but not elevated INR or bilirubin) cirrhosis are allowed.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- At least one measurable site of disease (as defined by Response Evaluation Criteria in Solid Tumors)
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- Patients with adequate bone marrow, liver and renal function
- Inability to tolerate first-line treatment with sorafenib
- Patient amenable to liver tumor biopsy
Who cannot join
- Child-Pugh B or Child-Pugh C cirrhosis
- Patients with known Gilbert's Syndrome
- Ongoing alcohol use or abuse defined as > an average of 2 alcoholic beverages daily
- Patients who have had major surgery within 4 weeks of initiation of study medication
- Patients with known brain metastases
- Patients with concurrent uncontrolled medical conditions that may interfere with their participation in the study
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- Patients with known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness
- Patients with Hepatitis B and/or Hepatitis C infection are excluded if they are on any of the following viral suppressive agents: boceprevir (Victrelis), ribavirin (Rebetol, Ribatab, Ribasphere), telaprevir (Incivek)
- Patients unable to take oral drugs or with lack of physical integrity of the upper gastrointestinal tract or known malabsorption syndromes
- Patients who have previously been treated with systemic LDE225 or with other Hh pathway inhibitors
- Patients who have neuromuscular disorders or are on concomitant treatment with drugs that are recognized to cause rhabdomyolysis
- Patients who are planning on embarking on a new strenuous exercise regimen after initiation of study treatment
- Patients who have taken part in an experimental drug study within 4 weeks of initiating study treatment with LDE225
- Patients who are receiving other anti-neoplastic therapy concurrently or within 2 weeks of starting study treatment with LDE225
- Patients who are receiving any anti-coagulation or anti-platelet therapy
- Patients who are receiving treatment with medications known to be strong inhibitors or inducers of cytochrome P450 3A4 (CYP3A4/5) or drugs metabolized by cytochrome P450 2B6 (CYP2B6) or cytochrome P450 2C9 (CYP2C9) that have narrow therapeutic index, and that cannot be discontinued before starting study treatment with LDE225
- Impaired cardiac function or clinically significant heart disease
- Patients with contraindications for MRI and/or MRI contrast agents
- Pregnant or nursing (lactating) women
- Women of child-bearing potential must use highly effective contraception during the study and through 6 months after the final dose of study treatment
- Sexually active males who are unwilling to use a condom during intercourse while taking drug and for 6 months after stopping investigational medications and agree not to father a child in this period
Trial locations and contacts
1 site in 1 country.
United States1 site
UCSD Moores Cancer Center
La Jolla, California, 92093
About this study
Official title: Phase Ib Study of Single Agent LDE225, an Oral Hedgehog Inhibitor, as Second-Line Therapy in Patients With Advanced or Metastatic Hepatocellular Carcinoma and Child-Pugh A/B7 Cirrhosis
The purpose of this study is to test the safety and determine the maximum safe dose of an experimental drug called LDE225 (hedgehog inhibitor) in people with liver cancer. We have identified hedgehog dysregulation as a novel mechanism for hepatocarcinogenesis and hepatic fibrosis/cirrhosis. Therefore, we hypothesize that the hedgehog inhibitor may be an ideal drug target for treating both hepatocellular carcinoma (HCC) and Child-Pugh A cirrhosis (CPA).
Read the detailed description
This is an open-label, single institution, Phase I, 3+3 dose escalation study of LDE225 in patients with advanced or metastatic hepatocellular carcinoma and Child-Pugh A Cirrhosis who are intolerant to sorafenib. The investigational treatment cycle (21 days) will consist of daily oral LDE225.
Dose escalation will be performed in serial patient cohorts. Up to six patients can be studied at each dose level. Safety and clinical data will be tabulated and the decision to open the next cohort level will be the responsibility of the principal investigator. Dose escalation will be based on the dose-limiting toxicities encountered through Day 42 of investigational treatment.
Patients will be dosed on a flat scale of daily dosing of LDE225 prescribed by the dose cohort.
- Conditions
- Hepatocellular Carcinoma, Cirrhosis
- Being tested
- LDE225
- Keywords
- liver cancer, cirrhosis, Child-Pugh A, Hedgehog
- Medical subject headings
- Carcinoma, Hepatocellular, Fibrosis, Liver Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LDE225Drug
Also called hedgehog inhibitor
LDE225 will be administered orally, on a continuous once daily dosing schedule at a dose determined by the cohort the patient is enrolled in until progression or unacceptable toxicity develops
| Study group | Role | What they receive |
|---|---|---|
| LDE225 | Experimental | LDE225 200mg-800mg oral daily Receives: Drug: LDE225 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of dose limiting toxicities
A dose limiting toxicity is a clinically significant adverse event (AE) occurring within 42 days of investigational treatment that is considered by the investigator to be possibly, probably, or definitely related to LDE225.
Measured: occurring within 42 days of investigational treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2014 (estimated)
- Study startJul 2014
- Primary completionDec 2016
- Study completionSep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jason K. Sicklick, M.D.
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Responsible party
- Sponsor-investigator, Jason K. Sicklick, M.D., University of California, San Diego
- Investigators
- Jason K. Sicklick, MD, Principal investigator, University of California Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02151864
- Sponsor's protocol ID
- 131053
- Status last verified
- Mar 2019
- First submitted
- 28 May 2014
- Last updated
- 5 Mar 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib Study of Single Agent LDE225, an Oral Hedgehog Inhibitor, as Second-Line Therapy in Patients With Advanced or Metastatic Hepatocellular Carcinoma and Child-Pugh A/B7 Cirrhosis
- ClinicalTrials.gov ID
- NCT02151864
- Acronym / sponsor ID
- 131053
- Conditions
- Hepatocellular Carcinoma, Cirrhosis
- Keywords
- liver cancer, cirrhosis, Child-Pugh A, Hedgehog
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Jason K. Sicklick, M.D.University, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Study start
- Jul 2014 (actual)
- Primary completion
- Dec 2016 (actual)
- Study completion
- Sep 2017 (actual)
- First posted
- 30 May 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to test the safety and determine the maximum safe dose of an experimental drug called LDE225 (hedgehog inhibitor) in people with liver cancer. We have identified hedgehog dysregulation as a novel mechanism for hepatocarcinogenesis and hepatic fibrosis/cirrhosis. Therefore, we hypothesize that the hedgehog inhibitor may be an ideal drug target for treating both hepatocellular carcinoma (HCC) and Child-Pugh A cirrhosis (CPA).
Detailed description
This is an open-label, single institution, Phase I, 3+3 dose escalation study of LDE225 in patients with advanced or metastatic hepatocellular carcinoma and Child-Pugh A Cirrhosis who are intolerant to sorafenib. The investigational treatment cycle (21 days) will consist of daily oral LDE225.
Dose escalation will be performed in serial patient cohorts. Up to six patients can be studied at each dose level. Safety and clinical data will be tabulated and the decision to open the next cohort level will be the responsibility of the principal investigator. Dose escalation will be based on the dose-limiting toxicities encountered through Day 42 of investigational treatment.
Patients will be dosed on a flat scale of daily dosing of LDE225 prescribed by the dose cohort.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| LDE225 | Experimental | Drug: LDE225LDE225 200mg-800mg oral daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age 18 years or older
- Pathological confirmation of advanced or metastatic HCC
- HCC not amenable to surgical resection, liver transplantation, chemoembolization, or ablation therapy
- Patients with Child-Pugh A and Child-Pugh B7 (if due to low albumin but not elevated INR or bilirubin) cirrhosis are allowed.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
Key exclusion criteria (21 listed)
- Child-Pugh B or Child-Pugh C cirrhosis
- Patients with known Gilbert's Syndrome
- Ongoing alcohol use or abuse defined as > an average of 2 alcoholic beverages daily
- Patients who have had major surgery within 4 weeks of initiation of study medication
- Patients with known brain metastases
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: hedgehog inhibitorLDE225 will be administered orally, on a continuous once daily dosing schedule at a dose determined by the cohort the patient is enrolled in until progression or unacceptable toxicity develops | Drug | LDE225 |
Primary outcome
Rate of dose limiting toxicities
Time frame: occurring within 42 days of investigational treatment
A dose limiting toxicity is a clinically significant adverse event (AE) occurring within 42 days of investigational treatment that is considered by the investigator to be possibly, probably, or definitely related to LDE225.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2019.
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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.
Jason K. Sicklick, MD principal investigator
University of California Medical Center
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 Hepatocellular Carcinoma and Cirrhosis, run by Jason K. Sicklick, M.D. 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 9 inclusion and 21 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 5 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Rate of dose limiting toxicities (time frame: occurring within 42 days of investigational treatment). 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 5 Mar 2019.