Basal Cell Nevus SyndromePhase 2GDC-0449NCT00957229
To Determine The Efficacy and Safety of GDC-0449 in Patients With Basal Cell Nevus Syndrome (BCNS)
A Phase 2 study testing GDC-0449 in people with Basal Cell Nevus Syndrome and Gorlin Syndrome, run by UCSF Benioff Children's Hospital Oakland at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 35 to 75 years
- Conditions the study is for
- Basal Cell Nevus Syndrome, Gorlin Syndrome
- What is being tested?
- GDC-0449
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 41 participants
- Where
- 2 sitesUnited States
- Study dates
- Aug 2009to Jan 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 13Show fewer
- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
New York, New York, 10032
Children's Hospital Oakland Research Institiute
Oakland, California, 94609
About this study
Official title: 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.
Read the detailed description
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.
- Conditions
- Basal Cell Nevus Syndrome, Gorlin Syndrome
- Being tested
- GDC-0449
- Medical subject headings
- Basal Cell Nevus Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GDC-0449Drug
Also called Hedgehog Inhibitor, Hedgehog Antagonist
capsule, 150 mg, one pill daily, 18 months
| Study group | Role | What they receive |
|---|---|---|
| Sugar pill | Placebo comparator | placebo pill by mouth once daily Receives: Drug: GDC-0449 |
| GDC-0449 | Experimental | vismodegib 150MG by mouth once daily Receives: Drug: GDC-0449 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of New Surgically Eligible Basal-cell Carcinomas
Number of new surgically eligible basal-cell carcinomas per patient per year
Measured: 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
Measured: Baseline and 18 months
Number of New Surgically Eligible Basal-cell Carcinomas After Stopping Vismodegib Treatment
The number of new surgically eligible basal-cell carcinomas per patient per month is reported.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2009 (estimated)
- Study startAug 2009
- Primary completionJan 2014
- Study completionJan 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Basal Cell Nevus SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- UCSF Benioff Children's Hospital Oakland
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- Ervin Epstein, MD, Principal investigator, UCSF Benioff Children's Hospital Oakland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00957229
- Sponsor's protocol ID
- 2009-026
- Other IDs
- SHH-4685s
- Acronym
- GDC-0449
- Status last verified
- Dec 2020
- First submitted
- 5 Aug 2009
- Last updated
- 11 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 22670904Ally 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.
PubMed 24623282Tang 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.
PubMed 27838224
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT00957229
- Acronym / sponsor ID
- GDC-0449 / 2009-026
- Conditions
- Basal Cell Nevus Syndrome, Gorlin Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- UCSF Benioff Children's Hospital OaklandUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- Aug 2009
- Primary completion
- Jan 2014 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 12 Aug 2009 (estimated)
- Results
- Posted 11 Jan 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sugar pill | Placebo comparator | Drug: GDC-0449placebo pill by mouth once daily |
| GDC-0449 | Experimental | Drug: GDC-0449vismodegib 150MG by mouth once daily |
Who may qualify
- Ages
- 35 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GDC-0449Also: Hedgehog Inhibitor, Hedgehog Antagonistcapsule, 150 mg, one pill daily, 18 months | Drug | GDC-0449, Sugar pill |
Primary outcome
Number of New Surgically Eligible Basal-cell Carcinomas
Time frame: 3 months of receiving study drug
Number of new surgically eligible basal-cell carcinomas per patient per year
2 secondary outcomes
Change in Size of the Existing Carcinomas, Expressed as the Sum of Cumulative Diameters in Millimeters Over an 18 Month Period
Time frame: Baseline and 18 months
Number of New Surgically Eligible Basal-cell Carcinomas After Stopping Vismodegib Treatment
Time frame: 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22670904Tang 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.
- Results publication: PubMed 24623282Ally 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.
- Results publication: PubMed 27838224Tang 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ervin Epstein, MD principal investigator
UCSF Benioff Children's Hospital Oakland
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GDC-0449 in people with Basal Cell Nevus Syndrome and Gorlin Syndrome, run by UCSF Benioff Children's Hospital Oakland at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of New Surgically Eligible Basal-cell Carcinomas (time frame: 3 months of receiving study drug). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00957229, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jan 2021.