• metastatic BCC with histologic confirmation of a distant BCC metastasis (e.g., lung, liver, lymph nodes, or bone) • locally advanced BCC considered inoperable or with medical contraindication to surgery • nevoid BCC syndrome (Gorlin syndrome), meeting the criteria for locally advanced or metastatic disease MedDRA version: 14.1 Level: PT Classification code 10004146 Term: Basal cell carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Vismodegib (GDC-0449)
Product Code: GDC-0449
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Vismodegib
CAS Number: 879085-55-9
Current Sponsor code: GDC-0449
Concentration unit:
Sponsors
Genentech, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Signed informed consents • Men and women age = 18 years • ECOG performance status 0, 1, or 2 • For patients with mBCC, histologic confirmation of distant BCC metastasis (e.g., lung, liver, lymph nodes, or bone), with metastatic disease that is RECIST measurable using CT or MRI • For patients with locally advanced BCC, at least one histologically confirmed lesion = 10 mm in the longest diameter that is considered to be inoperable or to have a medical contraindication to surgery (see below), in the opinion of a Mohs dermatologic surgeon, head and neck surgeon, or plastic surgeon • For patients with locally advanced BCC, radiotherapy must have been previously administered for their locally advanced BCC, unless radiotherapy is contraindicated or inappropriate (e.g., hypersensitivity to radiation due to genetic syndrome such as Gorlin syndrome, limitations because of location of tumor, or cumulative prior radiotherapy dose). For patients whose locally advanced BCC has been irradiated, disease must have progressed after radiation. • Patients with nevoid BCC syndrome (Gorlin syndrome) may enroll in this study but must meet the criteria for locally advanced or metastatic disease listed above. • For patients with locally advanced BCC, willingness to consent to biopsy of tumor(s) at baseline and during the study, as mandated by the protocol • For all patients, representative tumor specimens in paraffin blocks (preferred)or at least 15 unstained slides, with an associated pathology report, obtained at any time prior to entry of study • Adequate hematopoietic capacity, as defined by the following: Hemoglobin > 8.5 g/dL and not transfusion dependent Granulocyte count = 1000/µL Platelet count = 75,000/µL • Adequate hepatic function, as defined by the following: AST and ALT = 3 × the upper limit of normal (ULN) Total bilirubin = 1.5 × the ULN or within 3 × the ULN for patients with Gilbert disease • For women of childbearing potential, agreement to the use of two acceptable methods of contraception, including one barrier method, during the study and for 7 months after discontinuation of vismodegib • For men with female partners of childbearing potential, agreement to use a condom, and to advise their female partner to use an additional method of contraception during the study and for 7 months after discontinuation of vismodegib) • Agreement not to donate blood or blood products during the study and for 7 months after discontinuation of GDC-0449; for male patients, agreement not to donate sperm during the study and for 2 months after discontinuation of vismodegib Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: •Inability or unwillingness to swallow capsules •Prior treatment with Vismodegib or other antagonists of the Hh pathway •Pregnancy or lactation See Inclusion Criteria for women of childbearing potential and men withfemale partners of childbearing potential. Patients who are unable or are unwilling to adhere to the required contraceptive methods are excluded from the study. •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 (e.g., chemotherapy, other targeted therapy, topical therapy such as 5-fluorouracil or imiquimod, radiation therapy, or photodynamic therapy). For patients with multiple cutaneous BCCs at baseline that are not designated by the investigator as target lesions, treatment of these non-target BCCs with surgery may be permitted but must be discussed with the Medical Monitor prior to any surgical procedure. For patients with locally advanced BCC whose target lesion(s) is/are inoperable at baseline but is/are later deemed potentially operable because of tumor response to vismodegib, surgery with curative intent may be permitted but must be discussed with the Medical Monitor prior to any surgical procedure. •Recent (within 4 weeks of Day 1), current, or planned participation in an experimental drug study •History of other malignancies within 3 years of 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 •History of other 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 renders the patient at high risk from treatment complications
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is - to estimate the clinical benefit of Vismodegib given as therapy for patients with locally advanced or metastatic BCC, as measured by overall response rate (ORR).;Secondary Objective: The secondary objectives of this study are the following: • To estimate the duration of response, progression-free survival (PFS), and overall survival (OS) • To assess the safety and tolerability of vismodegib in this patient population • To assess the pharmacokinetics of vismodegib in this population (at participating sites only) • To assess patient-reported outcomes • To assess the histopathologic effect of vismodegib in tumor biopsies obtained at baseline and following vismodegib treatment in patients with locally advanced BCC • To evaluate the status of the Hh signaling pathway using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in archival tissue;Primary end point(s): The primary efficacy endpoint for this study is ORR. ORR will be assessed separately for patients with mBCC and locally advanced BCC: • For patients with metastatic BCC, RECIST will be used. • For patients with locally advanced BCC, a composite response endpoint will be used that incorporates externally visible tumor dimension and tumor ulceration, as well as RECIST for lesions with a RECIST-measurable component. In patients achieving a clinical response, tumor biopsies will be used in the final determination of complete versus partial response.;Timepoint(s) of evaluation of this end point: Objective response is defined as a complete or partial response determined on two consecutive assessments = 4 weeks apart and such patients will be referred to as ‘responders’. ORR will be defined as the proportion of responders. Patients without a post-baseline tumor assessment will be considered non-responders. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Duration of response, PFS, and OS PFS and OS will be defined from the time of first treatment with vismodegib. • The number and attribution of all adverse events (including vital signs, physical findings, and clinical laboratory results) in patients who receive any amount of study drug. • Steady-state plasma concentrations of vismodegib at Week 8 for patients enrolled at selected sites. • Change from Day 1 in patient-reported outcomes, as measured on the Short Form 36 (SF-36) Health Survey, Version 2 (see Appendix E) • Absence of residual BCC in patients with locally advanced BCC achieving a clinical response to vismodegib, as measured by independent pathological review • The relative expression of GLI1 and PTCH2 in archival tissue as measured by qRT PCR;Timepoint(s) of evaluation of this end point: Duration of PFS will be defined as the time from the initial dose of vismodegib until the earlier of documented disease progression or death within 30 days of last exposure to study treatment. Duration of OS will be defined as the time from the initial dose of vismodegib until death from any cause. | — |
Countries
Australia, Belgium, France, Germany, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line TISL
F. Hoffman-La Roche Ltd
Outcome results
None listed