To Determine The Efficacy and Safety of GDC-0449 in Patients With Basal Cell Nevus Syndrome (BCNS)

NCT00957229 | Completed Phase 2 Results DMC

• 2 other identifiers: 2009-026SHH-4685s
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Basal Cell Nevus Syndrome; Gorlin Syndrome

Outcome Measures

Primary Outcomes (1)

• Number of New Surgically Eligible Basal-cell Carcinomas

  Number of new surgically eligible basal-cell carcinomas per patient per year

  3 months of receiving study drug

Secondary Outcomes (2)

• Change in Size of the Existing Carcinomas, Expressed as the Sum of Cumulative Diameters in Millimeters Over an 18 Month Period

  Baseline and 18 months

• Number of New Surgically Eligible Basal-cell Carcinomas After Stopping Vismodegib Treatment

  These five patients were given placebo for a mean of 7.4 months (SD 2.3). After receiving vismodegib for a mean of 13.8 months (SD 6.8) and then discontinuing vismodegib for a mean of 11.8 months (SD 7.9) the new basal-cell carcinoma rate is reported.

Study Arms (2)

Sugar pill

PLACEBO COMPARATOR

placebo pill by mouth once daily

Drug: GDC-0449

GDC-0449

EXPERIMENTAL

vismodegib 150MG by mouth once daily

Drug: GDC-0449

Interventions

GDC-0449 DRUG

capsule, 150 mg, one pill daily, 18 months

Also known as: Hedgehog Inhibitor, Hedgehog Antagonist

GDC-0449; Sugar pill

Eligibility Criteria

• Age: 35 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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. 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

You may not qualify if:

• 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 to more than 5% of the skin (ii) retinoids systemically or topically to more than 5% of the skin during the six months prior to study entry; (iii) alpha-hydroxy acids to more than 5% of the skin during the six months prior to study entry (iv) 5-fluorouracil or imiquimod 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.
• 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.

Sponsors & Collaborators

• UCSF Benioff Children's Hospital Oakland: lead
• Genentech, Inc.: collaborator

Study Sites (2)

Children's Hospital Oakland Research Institiute

Oakland, California, 94609, United States

Location

Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

New York, New York, 10032, United States

Location

Related Publications (3)

• 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.

  PMID: 22670904 RESULT

• Ally MS, Tang JY, Joseph T, Thompson B, Lindgren J, Raphael MA, Ulerio G, Chanana AM, Mackay-Wiggan JM, Bickers DR, Epstein EH Jr. The use of vismodegib to shrink keratocystic odontogenic tumors in patients with basal cell nevus syndrome. JAMA Dermatol. 2014 May;150(5):542-5. doi: 10.1001/jamadermatol.2013.7444.

  PMID: 24623282 RESULT

• Tang JY, Ally MS, Chanana AM, Mackay-Wiggan JM, Aszterbaum M, Lindgren JA, Ulerio G, Rezaee MR, Gildengorin G, Marji J, Clark C, Bickers DR, Epstein EH Jr. Inhibition of the hedgehog pathway in patients with basal-cell nevus syndrome: final results from the multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2016 Dec;17(12):1720-1731. doi: 10.1016/S1470-2045(16)30566-6. Epub 2016 Nov 10.

  PMID: 27838224 RESULT

MeSH Terms

Conditions

Basal Cell Nevus Syndrome

Interventions

HhAntag691

Condition Hierarchy (Ancestors)

Odontogenic Cysts; Jaw Cysts; Bone Cysts; Cysts; Neoplasms; Carcinoma, Basal Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Basal Cell; Neoplastic Syndromes, Hereditary; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Jaw Diseases; Stomatognathic Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Results Point of Contact

• Title: Ervin H Epstein Jr., MD
• Organization: Children's Hospital of Oakland Research Institute, Oakland

eepstein@chori.org

510-450-5688

Study Officials

• Ervin Epstein, MD

  UCSF Benioff Children's Hospital Oakland

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2009
• First Posted: August 12, 2009
• Study Start: August 1, 2009
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: January 11, 2021
• Results First Posted: January 11, 2021

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)