A Pilot Study Of A Hedgehog Pathway Inhibitor (LDE-225) In Surgically Resectable Pancreas Cancer

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2012-09-24	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2014-12-10
First Submitted that Met QC Criteria 2012-09-24	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2014-12-12
First Posted (ESTIMATED) 2012-09-27	Results First Posted N/A	Last Verified 2014-12

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: LDE-225 LDE-225: dose - 800 mg, taken by mouth once daily for 2 weeks.	DRUG: LDE-225 LDE-225 capsules will be administered as a fixed dose of 800 mg daily for two weeks.

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: LDE-225

LDE-225: dose - 800 mg, taken by mouth once daily for 2 weeks.

DRUG: LDE-225

LDE-225 capsules will be administered as a fixed dose of 800 mg daily for two weeks.

Primary Outcome Measures	Measure Description	Time Frame
Changes in mean Gli-1 levels before and after drug	Means and variances of the (transformed) data for samples from stroma and tumor are calculated. Data is collected from patients in pairs (with the first observation from the biopsy prior to drug and the second after surgery, and after the drug), and it is expected these two observations will be correlated. Detectable differences for a range of four correlations will be computed.	2 years

Secondary Outcome Measures	Measure Description	Time Frame
Complications from surgery by time of hospital discharge up to 30 days post-operatively		2 years

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Patients with biopsy probable, resectable pancreatic cancer. Patients will be expected to undergo surgery a minimum of 14 days following signing consent.
Patients must give informed consent.
Patients must be over 18 and have an ECOG performance status ≤2 and life expectancy > 3 months.
Patients must have normal organ and marrow function as defined below:

ANC ≥1,500 /µL
Platelets ≥100,000 /µL
Hemoglobin>10gm/dl
creatinine <1.5 X ULN
Plasma creatine phosphokinase (CK) < 1.5 x ULN
PT/PTT WNL
Patients may have abnormal bilirubin, which is concluded by the surgeon to be related to biliary ductal obstruction, may be included if bilirubin < 3 X ULN.
Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) < 2.5 x upper limit of normal (ULN).

Poor surgical risk due to comorbidities or poor performance status
Patients who have received prior treatment with a smoothened antagonist, (GDC-0449 (Genentech), IPI-926 (Infinity).
Patients who have received chemotherapy within a period of time that is < the cycle length used for that treatment (e.g. <6 weeks for nitrosoureas, mitomycin-C) prior to starting study drug or who have not recovered from the side effects of such therapy
Patients who have received wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy.
Patients who have received biologic therapy (e.g. antibodies) ≤ 4 weeks prior to starting study drug or who have not recovered from the side effects of such therapy
Patients who have been treated with a targeted agent ≤ 5 t1/2 or ≤ 4 weeks (whichever is shorter) prior to starting study drug or who have not recovered from the side effects of such therapy
Patients who have received any other investigational agents ≤ 5 t1/2 or ≤ 4 weeks (whichever is shorter) prior to starting study drug or who have not recovered from the side effects of such therapy
Poor oral intake and/or inability to take capsules
Impairment of gastrointestinal function or gastrointestinal disease such as Chron's Disease or Ulcerative Cholitis, short-gut syndrome, celiac sprue disease that may significantly alter the absorption of LDE225
Urgent/emergent need for surgery (< 7 days)
Documented cirrhotic liver disease, ongoing alcohol abuse, or known active or acute hepatitis
Impaired cardiac function or clinically significant heart disease, including any one of the following:

Angina pectoris within 3 months
Acute myocardial infarction within 3 months
QTcF > 450 msec for males and > 470 msec for females 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. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
Patients who have had a venous thromboembolic event (e.g., pulmonary embolism or deep vein thrombosis) requiring anticoagulation
Presence of active infection or systemic use of antibiotics within 72 hours of enrollment.
Significant co-morbid condition or disease which in the judgment of the Investigator would place the patient at undue risk or interfere with the study. Examples include, but are not limited to sepsis, recent significant cardiac or pulmonary disease, or other conditions.
Known human immunodeficiency virus (HIV) positivity
Known hypersensitivity to LDE-225, or any of the excipients in LDE-225
Pregnant or lactating women.
Patients who are receiving treatment with medications known to be moderate and 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 at least 7 days and strong CYP3A/5 inducers for at least 2 weeks prior to starting treatment with LDE225.
Patients who have neuromuscular disorders (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy) or are on concomitant treatment with drugs that are recognized to cause rhabdomyolysis, such as HMG CoA inhibitors (statins), clofibrate and gemfibrozil, and that cannot be discontinued at least 2 weeks prior to starting LDE225 treatment. If it is essential that the patient stays on a statin to control hyperlipidemia, only pravastatin may be used with extra caution.

Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 4 months after stopping study treatment.
Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.
Sexually active males must use a condom during intercourse while taking the drug and for 6 months after stopping treatment and should not father a child in this period.
Patients unwilling or unable to comply with the protocol.

Collaborators and Investigators

Publications

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