A Single Arm, Phase II, Multicenter Study To Assess The Efficacy And Safety Of Vismodegib And Radiotherapy In Patients With High Risk Or Locally Advanced Basal Cell Carcinoma Not Amenable To Radical Surgery
Overview
- Phase
- Phase 2
- Intervention
- Vismodegib
- Conditions
- Carcinoma, Basal Cell
- Sponsor
- Istituto Clinico Humanitas
- Enrollment
- 14
- Locations
- 1
- Primary Endpoint
- evaluate the activity of the study therapy in terms of proportion of patients progression free
- Status
- Terminated
- Last Updated
- 6 years ago
Overview
Brief Summary
This is a Fleming-A' Hern, single arm, multicenter, no-profit, phase II study of radiotherapy and Vismodegib in adult patients with high risk or locally advanced basal cell carcinoma not amenable to radical surgery cell carcinoma (BCC) (comparator: not applicable).
The recruitment period is expected to be approximately 24 months. The trial will consist of a Screening/Baseline period (Day -28 to -1), a Treatment Period when patients will be treated with radiotherapy (4 weeks) followed by Vismodegib 150 mg/die continuously for six cycles (24 weeks).
The study will end 14 months after start of treatment of the last patient enrolled and evaluable according to primary end point.
Detailed Description
This is a Fleming-A' Hern, single arm, multicenter, no-profit, phase II study of radiotherapy and Vismodegib in adult patients with high risk or locally advanced basal cell carcinoma not amenable to radical surgery cell carcinoma (BCC) (comparator: not applicable). The recruitment period is expected to be approximately 24 months. The trial will consist of a Screening/Baseline period (Day -28 to -1), a Treatment Period when patients will be treated with radiotherapy (4 weeks) followed by Vismodegib 150 mg/die continuously for six cycles (24 weeks). The study will end 14 months after start of treatment of the last patient enrolled and evaluable according to primary end point. The primary objective is to evaluate the activity of the study therapy (radiotherapy followed by six cycles of Vismodegib 150 mg/d continuously) in terms of proportion of patients progression free at 12 months. The secondary objectives are: to evaluate the efficacy of the study therapy in terms of progression free survival (PFS) and overall survival (OS); to assess the response in terms of overall response rate (ORR) (complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD)); to assess duration of response (DoR); to assess the safety in terms of incidence, type, and severity of adverse events (AEs) and serious adverse events (SAEs) ;to measure the effects of skin disease on quality of life (QoL) of patients under therapy (Skindex-16)
Investigators
Eligibility Criteria
Inclusion Criteria
- •Written, signed informed consent
- •Age ≥ 18 years
- •Histopathologic confirmation that the lesion is BCC before enrollment
- •Patients with high risk of relapse BCC not undergone radical surgery, for which treating physician must consider the disease to be no more operable.
- •Clinical features defining high risk of relapse include infiltrative growth margins, size, tumor location, histological subtype (the morpheaform, the sclerosing, the infiltrating, the micronodular and the metatypical subtypes are associated with higher risk of relapse as compared to the risk associated with the superficial and the nodular types), recurrent-refractory tumors (see Table 1), basal cell carcinoma size (largest tumor diameter) ≤ 5 cm for head and neck tumors
- •Clinical features for definition of "BCC not amenable for radical surgery" include:
- •BCC that has recurred in the same location after minimum 2 surgical procedures (excluding biopsies) and/or curative resection is deemed unlikely
- •multifocal BCC or extensive tumors (see table 1) with bleeding or infected areas
- •anticipated substantial morbidity and/or deformity from surgery (e.g., removal of all or part of a facial structure, such as nose, ear, eyelid, eye; or requirement for limb amputation)
- •Patients with BCCs localized where surgery is technically difficult, or would result in unacceptable tissue destruction
Exclusion Criteria
- •Inability or unwillingness to swallow capsules
- •Inability or unwillingness to comply with study procedures
- •Pregnancy or lactation (lactation not allowed for at least 24 months after completion of study treatment)
- •Concurrent non-protocol-specified anti-tumor therapy (e.g., chemotherapy, other targeted therapy, photodynamic therapy, including participation in an experimental drug study)
- •Metastatic BCC
- •Gorlin Syndrome or any other contraindication to radiotherapy
- •Recent (i.e., within the past 28 days prior to enrollment in this study) or current participation in another experimental drug study
- •Uncontrolled medical illness, including advanced malignancies, at the discretion of the Investigator
- •History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect interpretation of the results of the study or renders the patient at high risk for treatment complications
Arms & Interventions
Vismodegib & Radiotherapy
Radiotherapy (RT) will be administered with a total dose of 50 Gy/2.5 Gy per fraction over 4 weeks. Treatment with Vismodegib will start within 4 weeks by the end of radiotherapy and will continue for 6 cycles
Intervention: Vismodegib
Vismodegib & Radiotherapy
Radiotherapy (RT) will be administered with a total dose of 50 Gy/2.5 Gy per fraction over 4 weeks. Treatment with Vismodegib will start within 4 weeks by the end of radiotherapy and will continue for 6 cycles
Intervention: Radiotherapy
Outcomes
Primary Outcomes
evaluate the activity of the study therapy in terms of proportion of patients progression free
Time Frame: 1 years
The primary objective is to evaluate the activity of the study therapy (radiotherapy followed by six cycles of Vismodegib 150 mg/d continuously) in terms of proportion of patients progression free at 12 months.
Secondary Outcomes
- evaluate the efficacy of the study therapy in terms of progression free survival(2 years)
- evaluate the efficacy of the study therapy in terms overall survival(2 years)
- response in terms of overall response rate (ORR)(2 years)
- duration of response(2 years)
- assess the safety in terms of incidence, type, and severity of adverse events (AEs) and serious adverse events (SAEs)(2 years)
- measure the effects of skin disease on quality of life (QoL) of patients(2 years)