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Pilot LDE225 in Locally Advanced or Metastatic BCC + Previously Tx Non-LDE225 Smoothened Inhibitors

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ClinicalTrials.gov Identifier: NCT01529450
Recruitment Status : Completed
First Posted : February 8, 2012
Results First Posted : November 2, 2016
Last Update Posted : January 16, 2017
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
Anne Chang, Stanford University

Tracking Information
First Submitted Date  ICMJE October 11, 2011
First Posted Date  ICMJE February 8, 2012
Results First Submitted Date  ICMJE March 11, 2016
Results First Posted Date  ICMJE November 2, 2016
Last Update Posted Date January 16, 2017
Study Start Date  ICMJE February 2012
Actual Primary Completion Date August 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 23, 2016)
Progression Free Survival (PFS) of All Participants [ Time Frame: End of treatment or at time of disease progression (up to 58 weeks) ]
Original Primary Outcome Measures  ICMJE
 (submitted: February 6, 2012)
Progression Free Survival (PFS) of individuals with locally advanced or metastatic BCC who have been previously treated with a non-LDE225 Smo inhibitor [ Time Frame: End of Treatment or 12 months whichever comes first ]
Change History Complete list of historical versions of study NCT01529450 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 23, 2016)
Molecular Markers Associated With Clinical Response [ Time Frame: Assessed on day 1 ]
Following consent, historical biopsy samples were analyzed for molecular markers associated with clinical response. Tumors were analyzed and present of Smooth mutation (SMO [genetic changes which influence Ki 67 and Gli levels]). was determined. The number of participants with and without SMO were reported by clinical outcome (SD = stable disease; PD = progressive disease).
Original Secondary Outcome Measures  ICMJE
 (submitted: February 6, 2012)
Biomarker levels of oral LDE225 on tumor tissue biomarkers of BCC activation (Gli 1, 2, Patched 1,2 and Ki67) in individuals which are non-naïve to Smo inhibitors other than LDE225 [ Time Frame: End of treatment or 12 months whichever comes first ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pilot LDE225 in Locally Advanced or Metastatic BCC + Previously Tx Non-LDE225 Smoothened Inhibitors
Official Title  ICMJE A Pilot Open-Label Study to Examine the Safety and Efficacy of Oral LDE225 in Patients With Locally Advanced or Metastatic Basal Cell Carcinoma Who Have Been Previously Treated With Non-LDE225 Smoothened Inhibitor(s)
Brief Summary

This is a prospective single-center, open label, pilot study to investigate the safety and efficacy of LDE225 in patients with locally advanced or metastatic basal cell carcinoma.

Primary Objectives:

• To explore the effects of oral LDE225 on the Progression Free Survival (PFS) of individuals with locally advanced or metastatic BCC who have been previously treated with a non-LDE225 Smo inhibitor.

Secondary Objectives:

  • To evaluate the effect of oral LDE225 on tumor tissue biomarkers of BCC activation (Gii 1, 2, Patched 1,2 and Ki67) in individuals which are non-na"ive to Smo inhibitors other than LDE225, at baseline and at end-of-treatment
  • To describe adverse effects of oral LDE225 in individuals with a history of non-LDE225 Smo inhibitor usage
  • To assess the overall survival rates of individuals with locally advanced BCC or metastatic BCC who have previously taken a non-LDE225 Smo inhibitor after treatment with LDE225
Detailed Description

This is a prospective single-center, open label, pilot study to investigate the safety and efficacy of LDE225 in patients with locally advanced or metastatic basal cell carcinoma.

Primary Objectives:

• To explore the effects of oral LDE225 on the Progression Free Survival (PFS) of individuals with locally advanced or metastatic BCC who have been previously treated with a non-LDE225 Smo inhibitor.

Secondary Objectives:

  • To evaluate the effect of oral LDE225 on tumor tissue biomarkers of BCC activation (e.g. Gli and Ki67) in individuals which are non-naive to Smo inhibitors other than LDE225, at baseline and at end-of-treatment
  • To describe adverse effects of oral LDE225 in individuals with a history of non-LDE225 Smo inhibitor usage
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Basal Cell Carcinoma
Intervention  ICMJE Drug: LDE225
800-mg (4 200-mg capsules/day) capsule
Other Name: NVP-LDE225
Study Arms  ICMJE
  • Active Comparator: Refractory Group
    Patients previously treated with non-LDE225 Smo inhibitor who were refractory.
    Intervention: Drug: LDE225
  • Active Comparator: Resistance Developed Group
    Patients previously treated with non-LDE225 Smo inhibitor who were initially responsive but became resistant with progressive disease.
    Intervention: Drug: LDE225
Publications * Danial C, Sarin KY, Oro AE, Chang AL. An Investigator-Initiated Open-Label Trial of Sonidegib in Advanced Basal Cell Carcinoma Patients Resistant to Vismodegib. Clin Cancer Res. 2016 Mar 15;22(6):1325-9. doi: 10.1158/1078-0432.CCR-15-1588. Epub 2015 Nov 6.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 2, 2013)
11
Original Estimated Enrollment  ICMJE
 (submitted: February 6, 2012)
22
Actual Study Completion Date  ICMJE August 2013
Actual Primary Completion Date August 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Age 18 years or older.
  2. Histologically documented diagnosis of basal cell carcinoma deemed to be locally advanced or metastatic who have previously received a non-LDE225 Smo inhibitor.
  3. World Health Organization (WHO) performance status <= 2
  4. At least one measurable site of disease (as defined by Response Evaluation Criteria in Solid Tumors), or other disease specific response assessment criteria, as appropriate. State age restriction and/or gender/race-ethnic restrictions.
  5. Patients with adequate bone marrow, liver and renal function, as specified below:

    • Absolute Neutrophil Count (ANC) >= 1.5 x 10^9/L
    • Hemoglobin (Hgb) >= 9 g/dL
    • Platelets >= 80 x 10^9/L
    • Serum total bilirubin <= 1.5 x upper limit of normal (ULN)
    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 2.5 x ULN or <= 5 x ULN if liver metastases are present
    • Plasma creatine phosphokinase (CK) < 1.5 x ULN
    • Serum creatinine <= 1.5 x ULN or 24-hour clearance >= 50ml/min
  6. Written informed consent obtained prior to any screening procedures

Exclusion Criteria:

  1. Patients who have had major surgery within 4 weeks of initiation of study medication.
  2. Patients with concurrent uncontrolled medical conditions that may interfere with their participation in the study or potentially affect the interpretation of the study data.

    State restrictions regarding use of other Investigational Agents.

  3. Patients unable to take oral drugs or with lack of physical integrity of the upper gastrointestinal tract or known malabsorption syndromes.

    State exclusion requirements due to co-morbid disease or incurrent illness, as needed.

  4. Patients who have previously been treated with systemic LDE225.
  5. 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 3-hydroxy-3-methylglutaryl-coenzyme A (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.

    b) Patients who are planning on embarking on a new strenuous exercise regimen after initiation of study treatment. Note: Muscular activities, such as strenuous exercise, that can result in significant increases in plasma CK levels should be avoided whilst on LDE225 treatment.

  6. Patients who have taken part in an experimental drug study within 4 weeks of initiating treatment with LDE225.
  7. Patients who are receiving other anti-neoplastic therapy (e.g. chemotherapy, targeted therapy or radiotherapy) concurrently or within 2 weeks of starting treatment with LDE225.
  8. Patients who are receiving treatment with medications known to be moderate and strong inhibitors or inducers of cytochrome (CYP)3A4/5 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.
  9. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test (> 5 mIU/mL).

10 Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they are using two birth control methods. The two methods can be a double barrier method or a barrier method plus a hormonal method. Adequate barrier methods of contraception include:

  • Diaphragm, condom (by the partner), intrauterine device (copper or hormonal), sponge or spermicide. Hormonal contraceptives include any marketed contraceptive agent that includes an estrogen and/or a progestational agent.
  • Reliable contraception should be maintained throughout the study and for 3 months after study drug discontinuation.

    11 Patients unwilling or unable to comply with the protocol.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01529450
Other Study ID Numbers  ICMJE SKIN0009
SU-09022011-8371 ( Other Identifier: Stanford University )
21759 ( Other Identifier: Stanford IRB )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Anne Chang, Stanford University
Study Sponsor  ICMJE Anne Chang
Collaborators  ICMJE Novartis
Investigators  ICMJE
Principal Investigator: Anne Chang, MD Stanford University
PRS Account Stanford University
Verification Date November 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP