A Study Evaluating the Efficacy and Safety of Vismodegib (GDC-0449, Hedgehog Pathway Inhibitor) in Patients With Advanced Basal Cell Carcinoma

NCT00833417 | Completed Phase 2 Results

• 2 other identifiers: SHH4476gGO01541
• Study Type: interventional
• Target: 104
• Locations: 6 countries
• Sites: 35

Brief Summary

This was a Phase II, single-arm, two-cohort multicenter clinical trial evaluating the efficacy and safety of vismodegib (GDC-0449) in patients with advanced basal cell carcinoma. All patients received vismodegib until evidence of progression, intolerable toxicities most probably attributable to vismodegib, or withdrawal from the study.

Conditions

Basal Cell Carcinoma

Keywords

BCC; Hedgehog Pathway Inhibitor; Hedgehog; Basal Cell Cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response (OR) Determined by the Independent Review Facility

  OR=complete (CR) or partial response (PR). Metastatic-CR:Disappearance of all targets. PR:≥30% decreased sum of longest diameter (SLD) of targets compared to baseline (B). Locally advanced-Response=No progressive disease (PD) and ≥30% decreased SLD from baseline (radiography \[R\]) or ≥30% decreased SLD from B (externally visible dimension \[EVD\]) or completely resolved ulceration. CR:Response with no residual BCC on tumor biopsy (otherwise response was PR). PD:Any of ≥20% increased SLD from nadir (R or EVD), new ulceration, new lesions (R or physical exam) or non-target lesion progression by R.

  From study initiation (enrollment of first patient) through 9 months following the first treatment of the last enrolled patient (clinical cutoff date of 26 November 2010), up to 90 weeks

Secondary Outcomes (5)

• Duration of Objective Response (OR) Determined by the Independent Review Facility

  From study initiation (enrollment of first patient) through 9 months following the first treatment of the last enrolled patient (clinical cutoff date of 26 November 2010), up to 90 weeks

• Progression-free Survival (PFS) Determined by the Independent Review Facility

  From study initiation (enrollment of first patient) through 9 months following the first treatment of the last enrolled patient (clinical cutoff date of 26 November 2010), up to 90 weeks

• Overall Survival

  From study initiation (enrollment of first patient) through 9 months following the first treatment of the last enrolled patient (clinical cutoff date of 26 November 2010), up to 90 weeks

• Change From Baseline in Short Form 36 (SF-36) Health Survey Scores

  Baseline, Week 12, Week 24, and at the end of the study or early termination visit, up to 90 weeks

• Percentage of Patients With Absence of Residual Basal Cell Carcinoma (BCC) in Patients With Locally Advanced BCC

  From baseline through end of the study, up to 90 weeks

Study Arms (1)

Vismodegib 150 mg

EXPERIMENTAL

Patients received vismodegib 150 mg orally once daily until disease progression; intolerable toxicity, most probably attributable to vismodegib; or withdrawal from the study.

Drug: Vismodegib 150 mg

Interventions

Vismodegib 150 mg DRUG

Vismodegib 150 mg was provided in hard gelatin capsules.

Also known as: GDC-0449

Vismodegib 150 mg

Eligibility Criteria

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

You may qualify if:

• Men and women ≥ 18 years of age.
• For patients with metastatic basal cell carcinoma (BCC), histological confirmation of distant BCC metastasis (eg, lung, liver, lymph nodes, or bone), with metastatic disease that is Response Evaluation Criteria in Solid Tumors (RECIST) measurable using computed tomography (CT) or magnetic resonance imaging (MRI).
• For patients with locally advanced BCC, histologically confirmed disease that is considered to be inoperable.
• For patients with locally advanced BCC, radiotherapy must have been previously administered for their locally advanced BCC, unless radiotherapy is contraindicated or inappropriate. For patients whose locally advanced BCC has been irradiated, disease must have progressed after radiation.
• For women of childbearing potential, agreement to the use of two acceptable methods of contraception, including one barrier method, during the study and for 12 months after discontinuation of vismodegib (GDC-0449).
• For men with female partners of childbearing potential, agreement to use a latex condom, and to advise their female partner to use an additional method of contraception during the study and for 3 months after discontinuation of vismodegib.

You may not qualify if:

• Prior treatment with vismodegib or other Hedgehog pathway inhibitors.
• Pregnancy or lactation.
• Life expectancy of \< 12 weeks.
• Patients with superficial multifocal BCC who may be considered unresectable due to breadth of involvement.
• Concurrent non-protocol-specified anti-tumor therapy (eg, chemotherapy, other targeted therapy, radiation therapy, or photodynamic therapy).
• Recent, current, or planned participation in an experimental drug study.
• History of other malignancies within 3 years of the first day of treatment with vismodegib in this study (Day 1), except for tumors with a negligible risk for metastasis or death, such as adequately treated squamous-cell carcinoma of the skin, ductal carcinoma in situ of the breast, or carcinoma in situ of the cervix.
• Uncontrolled medical illnesses such as infection requiring treatment with intravenous antibiotics.

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (35)

Unknown Facility

Scottsdale, Arizona, 85259, United States

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Los Angeles, California, 90025, United States

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San Francisco, California, 94115, United States

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Stanford, California, 94305, United States

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Aurora, Colorado, 80045, United States

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Ormond Beach, Florida, 32174, United States

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Chicago, Illinois, 60611, United States

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Sioux City, Iowa, 51101, United States

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Baltimore, Maryland, 21231-1000, United States

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Boston, Massachusetts, 02114, United States

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Boston, Massachusetts, 02215, United States

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Rochester, Minnesota, 55905, United States

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Las Vegas, Nevada, 89103, United States

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Lebanon, New Hampshire, 03756, United States

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New York, New York, 10029, United States

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Chapel Hill, North Carolina, 27599-7305, United States

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Columbus, Ohio, 43210, United States

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Philadelphia, Pennsylvania, 19104, United States

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Nashville, Tennessee, 37203, United States

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Houston, Texas, 77030-4095, United States

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Kogarah, New South Wales, 2217, Australia

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Melbourne, 3002, Australia

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Woolloongabba, 4102, Australia

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Brussels, 1000, Belgium

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Wilrijk, 2610, Belgium

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Lille, 59037, France

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Nantes, 44093, France

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Paris, 75010, France

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Pierre-Bénite, 69495, France

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Essen, 45122, Germany

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Kiel, 24105, Germany

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Tübingen, 72076, Germany

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Würzburg, 97080, Germany

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London, SW3 6JJ, United Kingdom

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Unknown Facility

Poole, BH15 2JB, United Kingdom

Location

Related Publications (3)

• Sekulic A, Migden MR, Basset-Seguin N, Garbe C, Gesierich A, Lao CD, Miller C, Mortier L, Murrell DF, Hamid O, Quevedo JF, Hou J, McKenna E, Dimier N, Williams S, Schadendorf D, Hauschild A; ERIVANCE BCC Investigators. Long-term safety and efficacy of vismodegib in patients with advanced basal cell carcinoma: final update of the pivotal ERIVANCE BCC study. BMC Cancer. 2017 May 16;17(1):332. doi: 10.1186/s12885-017-3286-5.

  PMID: 28511673 DERIVED

• Chang AL, Arron ST, Migden MR, Solomon JA, Yoo S, Day BM, McKenna EF, Sekulic A. Safety and efficacy of vismodegib in patients with basal cell carcinoma nevus syndrome: pooled analysis of two trials. Orphanet J Rare Dis. 2016 Sep 1;11(1):120. doi: 10.1186/s13023-016-0506-z.

  PMID: 27581207 DERIVED

• Sekulic A, Migden MR, Oro AE, Dirix L, Lewis KD, Hainsworth JD, Solomon JA, Yoo S, Arron ST, Friedlander PA, Marmur E, Rudin CM, Chang AL, Low JA, Mackey HM, Yauch RL, Graham RA, Reddy JC, Hauschild A. Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med. 2012 Jun 7;366(23):2171-9. doi: 10.1056/NEJMoa1113713.

  PMID: 22670903 DERIVED

MeSH Terms

Conditions

Carcinoma, Basal Cell; Neoplasms, Basal Cell

Interventions

HhAntag691

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Results Point of Contact

• Title: Medical Communications
• Organization: Genentech, Inc.

800-821-8590

Study Officials

• Jeannie Hou, M.D.

  Genentech, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2009
• First Posted: February 2, 2009
• Study Start: February 1, 2009
• Primary Completion: November 1, 2010
• Study Completion: April 1, 2014
• Last Updated: May 20, 2015
• Results First Posted: April 30, 2012

Record last verified: 2015-05

Locations

US (20); BE (2); AU (3); DE (4); GB (2); FR (4)