The Purpose of This Study is to Determine The Efficacy and Safety of a Systemic Hedgehog Pathway Antagonist (GDC-0449) in Patients With Basal Cell Nevus Syndrome (BCNS)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Genentech
Information provided by (Responsible Party):
Rajnesh Prasad, MBA, Children's Hospital & Research Center Oakland
ClinicalTrials.gov Identifier:
NCT00957229
First received: August 5, 2009
Last updated: February 19, 2013
Last verified: February 2013

August 5, 2009
February 19, 2013
August 2009
January 2014   (final data collection date for primary outcome measure)
OBJECTIVES Primary: - To evaluate the efficacy of GDC-0449 in reducing new surgically eligible BCCs in BCNS patients during month 3-18 of ingestion of 150 mg/day. - To evaluate the safety of this dose of GDC-0449 in these patients [ Time Frame: Monthly ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT00957229 on ClinicalTrials.gov Archive Site
Secondary: - To assess the effect of GDC-0449 in reducing the total number of BCCs of diameter 5mm or greater on the upper back. - To determine the duration of any anti-BCC effect of GDC-0449 after administration of the drug is stopped. [ Time Frame: Effacacy will assessed at 1 year and duration of anti-BCC effect will be assessed 6 months after study med is stopped. ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
The Purpose of This Study is to Determine The Efficacy and Safety of a Systemic Hedgehog Pathway Antagonist (GDC-0449) in Patients With Basal Cell Nevus Syndrome (BCNS)
A Randomized, Phase II Multicenter Trial Evaluating the Efficacy and Safety of a Systemic Hedgehog Pathway Antagonist (GDC-0449) in Patients With Basal Cell Nevus Syndrome (BCNS)

The purpose of this study is to reduce the number of new surgically eligible BCCs by 50% appearing during month 3-18 of medication ingestion.

This is a Phase II, 18 month, double blind, randomized placebo-controlled, two arm multicenter clinical study design. During the 18-month treatment period, the safety and chemopreventive efficacy of 150 mg/day GDC-0449 versus placebo will be assessed, and include evaluations of the skin at monthly intervals for the first three months and then every 3 months for the next 15 months. Removal of new surgically eligible BCCs (SEBs) will be done by primary skin care physicians (PSCPs) or at Study Centers. A Data Safety Monitoring Board (DSMB) will review unblinded results for an interim analysis when 20 subjects have completed 12 months of drug. This review will focus on adverse events and efficacy results. Subjects will be monitored for the development of new SEBs after they discontinue study treatment. At the end of the 18 months, given that the observed adverse events are minimal, patients on placebo will be offered the opportunity to take GDC-0449 for 18 months in an open label continuation, followed by six months observation, and patients on GDC449 will be monitored for the next 24 months for assessment of the duration of benefit after stopping the drug.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Basal Cell Nevus Syndrome
  • Gorlin Syndrome
Drug: GDC-0449
capsule, 150 mg, one pill daily, 18 months
Other Names:
  • Hedgehog Inhibitor
  • Hedgehog Antagonist
  • Placebo Comparator: Sugar pill
    Intervention: Drug: GDC-0449
  • Experimental: GDC-0449
    Intervention: Drug: GDC-0449
Tang JY, Mackay-Wiggan JM, Aszterbaum M, Yauch RL, Lindgren J, Chang K, Coppola C, Chanana AM, Marji J, Bickers DR, Epstein EH Jr. Inhibiting the hedgehog pathway in patients with the basal-cell nevus syndrome. N Engl J Med. 2012 Jun 7;366(23):2180-8. doi: 10.1056/NEJMoa1113538.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
41
January 2015
January 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

The subject:

  • has had diagnosed at least 10 SEB (of diameter 3 mm diameter or greater on the nose or periorbital skin, 5 mm or greater elsewhere on the face, or 9 mm or greater on non-facial areas excluding the skin below the knees) during the two years before study entry, as documented histologically in physicians' records and/or diagnosed clinically by a Study Investigator at baseline.
  • meet diagnostic criteria for basal cell nevus syndrome
  • is willing to abstain from application of non-study topical medications to the skin for the duration of the study, including prescription and over the counter preparations. For example, topical preparations containing corticosteroids (other than Triamcinolone applied no more than 6x/month) or vitamin A derivatives are not allowed. Moisturizers and emollients are allowable. Subjects will be encouraged to use sunscreen (SPF 15) at least once daily on all exposed skin sites.
  • is willing to forego treatment of BCCs unless the BCCs are documented by Study Investigators, preferably on two separate visits, except when the PSCP believes that delay in treatment potentially might compromise the health of the subject.
  • has normal laboratory tests as defined by the following: Normal hematopoietic capacity, Normal hepatic function: AST and ALT greater than or equal to 2x the upper limit of normal (ULN) Total bilirubin within normal range 0.20 mg/dl to 1.50 mg/dl or within 3x ULN for patients with Gilbert's disease Normal renal function: normal serum creatinine or measured creatinine clearance less than 50 mL/minute. Fasting cholesterol greater than or equal to 220 untreated
  • be willing to not donate blood or semen for three months following discontinuation of Study medications.
  • is willing to avoid pregnancy in his partner as defined by the following: Male subject is willing to use a latex condom during the study and for 3 months after the last dose during sexual contact with a female of childbearing potential, even if he has had a successful vasectomy. His partner must also use a form of birth control

Exclusion Criteria:

The subject:

  • has used topical or systemic therapies that might interfere with the evaluation of the study medication during the study. Specifically these include the use of: (i) glucocorticoids (other than Triamcinolone on no more than 36 days during the six months prior to study entry) to more than 5% of the skin (ii) retinoids (e.g., etretinate, isotretinoin, tazarotene, tretinoin, adapalene) systemically or topically to more than 5% of the skin during the six months prior to study entry; (iii) alpha-hydroxy acids (e.g., glycolic acid, lactic acid) to more than 5% of the skin during the six months prior to study entry (iv) 5-fluorouracil or imiquimod (except as topical treatment to discrete BCCs) systemically or topically to the skin above the knees during the six months prior to study entry. (v) treatment with systemic chemotherapy within one year prior to starting study medication.
  • has a history of hypersensitivity to any of the ingredients in the study medication formulations.
  • is unable to return for follow-up visits and tests.
  • has uncontrolled systemic disease, including known HIV positive patients.
  • has history of congestive heart failure.
  • has uncontrolled hypocalcemia, hypomagnesemia, or hypokalemia
  • has clinically important history of liver disease, including viral or hepatitis, current alcohol abuse, or cirrhosis.
  • has any condition or situation which in the Investigator's opinion may put the subject at significant risk, could confound the study results, or could interfere significantly with the subject's participation in the study. This includes history of other skin conditions or disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or that might affect interpretation of the results of the study or render the patient at high risk from treatment complications
  • has a history of invasive cancer within the past five years excluding non-melanoma skin cancer, Stage I cervical cancer, ductal carcinoma in situ of the breast, or CLL Stage 0.
  • has current, recent (within 4 weeks of Day 1), or planned participation in an experimental drug study while enrolled in this study.
  • is a female who is pregnant, plans to ever to become pregnant, capable of becoming pregnant or is breast feeding.
  • is a male who is unwilling or unable to comply with pregnancy prevention measures.
Both
35 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00957229
2009-026, SHH-4685s
Yes
Rajnesh Prasad, MBA, Children's Hospital & Research Center Oakland
Children's Hospital & Research Center Oakland
Genentech
Principal Investigator: Ervin Epstein, MD Children's Hospital & Research Center Oakland
Children's Hospital & Research Center Oakland
February 2013

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