Trial Comparing the Effects of Intermittent Vismodegib Versus Photodynamic Therapy in Patients With Multiple Basal Cell Carcinomas

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Genentech
Information provided by (Responsible Party):
Children's Hospital & Research Center Oakland
ClinicalTrials.gov Identifier:
NCT01556009
First received: March 14, 2012
Last updated: July 30, 2013
Last verified: July 2013
  Purpose

The purpose of this study is to evaluate and compare the safety and efficacy of intermittent vismodegib and of Photodynamic Therapy (PDT).


Condition Intervention Phase
Basal Cell Nevus Syndrome
Gorlin's Syndrome
Drug: GDC-0449
Procedure: Aminolevulinic acid %20 topical solution + blue light
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Randomized, Open Label Trial Comparing the Effects of Intermittent Vismodegib Versus Photodynamic Therapy on the Maintenance of Benefit Following 7 Months of Continuous Vismodegib Treatment in Patients With Multiple Basal Cell Carcinomas

Resource links provided by NLM:


Further study details as provided by Children's Hospital & Research Center Oakland:

Primary Outcome Measures:
  • Time to recurrence to baseline SEB burden following 7 months of continuous vismodegib treatment. [ Time Frame: A Data Safety Monitoring Board (DSMB) will review results for an interim analysis when 12 subjects have completed 28 months. ] [ Designated as safety issue: Yes ]

    Primary:

    i. To compare the efficacy of (i) intermittent vismodegib vs. (ii) the efficacy of photodynamic therapy (PDT) in preventing the return of the burden of surgically eligible BCCs (SEBs) to baseline level following 7 months of continuous vismodegib therapy.

    ii. To compare the cumulative diameter (burden) of SEBs in patients treated intermittently with vismodegib vs. with photodynamic therapy (PDT).



Secondary Outcome Measures:
  • The cumulative diameter (burden) of SEBs in patients treated intermittently with vismodegib vs PDT during months 8-28 maintenance period. [ Time Frame: A Data Safety Monitoring Board (DSMB) will review results for an interim analysis when 12 subjects have completed 28 months. ] [ Designated as safety issue: Yes ]

    i. To assess the safety of intermittent vismodegib in patients with multiple BCCs (BCNS and non-BCNS) during months 8-28.

    ii. To assess resistance of SEBs to treatments in patients with multiple BCCs (BCNS and non-BCNS) treated intermittently during months 8-28.

    iii. To assess the degree of reduction of SEBs after 7 months of continuous daily vismodegib therapy.

    iv. To conduct an exploratory evaluation in non-BCNS patients with multiple BCCs (high burden of disease) of the efficacy and tolerability of intermittent vismodegib vs PDT



Estimated Enrollment: 24
Study Start Date: April 2012
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Drug (Vismodegib)
Vismodegib is a small molecule inhibitor of SMO developed by Genentech for treatment of tumors in which the HH signaling pathway appears to contribute to development and maintenance of tumorigenesis. Vismodegib, a systemic HH pathway antagonist, has been shown to have oral bioavailability and potent anti-tumor activity in a variety of primary human tumor xenografts and tumor cell line xenograft models (see the Vismodegib Investigator Brochure).
Drug: GDC-0449
150 mg per day for 7 continuous months then randomized for 3 month intervals to 28 months.
Other Name: Erivedge
Experimental: Photodyanmic Therapy

Levulan(aminolevulinic acid HCl) is a drug that has come into prominence over the last two decades for its potential use in photodynamic therapy (PDT) of superficial, benign and malignant skin disorders. Aminolevulinic acid (ALA) is the natural precursor of protoporphyrin IX (PpIX) in the biosynthetic pathway leading to heme; it has been estimated that at least 358 mg ALA per day are synthesized by the human body to support endogenous heme production.

A New Drug Application (NDA) for treatment of non-hyperkeratotic actinic keratoses of the face or scalp with Levulan Kerastick for Topical Solution, 20% and 10 J/cm2 of visible (417 nm) blue light, was approved by the United States Food and Drug Administration (FDA) on December 03, 1999.

Procedure: Aminolevulinic acid %20 topical solution + blue light
Randomized for 3 month intervals beginning month 7 until month 28, 3 hour treatment every 4 weeks.
Other Name: Levulan

Detailed Description:

This is a Phase II, 28 month, randomized, two arm multicenter clinical study design. During the initial 7 months of the study, all 24 subjects will receive vismodegib, 150mg/day. They then will be randomized in a 1:1 ratio to receive intermittent vismodegib, 150 mg/day, during months 10-13, 16-19, and 22-25 or to receive treatment with PDT at month 10 and at three month intervals thereafter. The safety and efficacy of intermittent vismodegib and of PDT will be assessed at the time of the subjects' visits to the Study Center and at the time of telephone contacts. A Data Safety Monitoring Board (DSMB) will review results for an interim analysis when 12 subjects have completed 28 months. The DSMB review will focus on adverse events and efficacy results. Subjects will be monitored for the presence of surrogate endpoint biomarkers (SEBs) at each Study visit.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01556009

Locations
United States, California
Children's Hospital Research Center Oakland
Oakland, California, United States, 94609
Sponsors and Collaborators
Children's Hospital & Research Center Oakland
Genentech
Investigators
Principal Investigator: Ervin Epstein, MD Children's Hospital Research Institute
  More Information

No publications provided

Responsible Party: Children's Hospital & Research Center Oakland
ClinicalTrials.gov Identifier: NCT01556009     History of Changes
Other Study ID Numbers: 2011-077, ML28244
Study First Received: March 14, 2012
Last Updated: July 30, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Children's Hospital & Research Center Oakland:
Basal Cell Carcinoma
Photodynamic Therapy

Additional relevant MeSH terms:
Basal Cell Nevus Syndrome
Eye Abnormalities
Tooth Abnormalities
Carcinoma
Carcinoma, Basal Cell
Hamartoma Syndrome, Multiple
Odontogenic Cysts
Jaw Cysts
Bone Cysts
Cysts
Neoplasms
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
Genetic Diseases, Inborn
Eye Diseases
Stomatognathic System Abnormalities
Tooth Diseases
Hamartoma
Neoplasms, Multiple Primary
Aminolevulinic Acid
Photosensitizing Agents

ClinicalTrials.gov processed this record on April 17, 2014