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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)

Phase 2
35 Years
75 Years
Open (Enrolling)
Basal Cell Nevus Syndrome, Gorlin Syndrome

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Trial Information

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)

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.

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

- 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.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

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

Outcome Time Frame:


Safety Issue:


Principal Investigator

Ervin Epstein, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Hospital & Research Center Oakland


United States: Food and Drug Administration

Study ID:




Start Date:

August 2009

Completion Date:

January 2015

Related Keywords:

  • Basal Cell Nevus Syndrome
  • Gorlin Syndrome
  • Basal Cell Nevus Syndrome
  • Eye Abnormalities
  • Tooth Abnormalities
  • Nevus
  • Nevus, Pigmented



Children's Hospital Oakland Research Institiute Oakland, California  94609