To Assess The Efficacy And Safety Of Vismodegib And Radiotherapy In Advanced Basal Cell Carcinoma

NCT02956889 | Terminated Phase 2

• 1 other identifier: ONC-2015-001
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

Carcinoma, Basal Cell

Keywords

Carcinoma, Basal Cell; Vismodegib; Radiotherapy

Outcome Measures

Primary Outcomes (1)

• evaluate the activity of the study therapy in terms of proportion of patients progression free

  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.

  1 years

Secondary Outcomes (6)

• 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

Study Arms (1)

Vismodegib & Radiotherapy

EXPERIMENTAL

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

Drug: Vismodegib; Radiation: Radiotherapy

Interventions

Vismodegib DRUG

Patients will receive a continuous once-daily oral dosing of Vismodegib at a dosage of 150 mg .

Also known as: Erivedge

Vismodegib & Radiotherapy

Radiotherapy RADIATION

Radiotherapy (RT) will be administered with a total dose of 50 Gy/2.5 Gy per fraction over 4 weeks.

Vismodegib & Radiotherapy

Eligibility Criteria

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

You may qualify if:

• 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
• Patients with a clinical contraindication to surgery
• Previous radiotherapy on other BCC
• Patients with measurable and/or non-measurable disease (as defined by RECIST, v1.1) are allowed
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Adequate hematopoietic capacity, defined as the following:

You may not qualify if:

• 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

Sponsors & Collaborators

• Istituto Clinico Humanitas: lead

Study Sites (1)

Istituto Clinico humanitas

Rozzano, Mi, 20089, Italy

Location

Related Publications (9)

• Diffey BL, Langtry JA. Skin cancer incidence and the ageing population. Br J Dermatol. 2005 Sep;153(3):679-80. doi: 10.1111/j.1365-2133.2005.06799.x. No abstract available.

  PMID: 16120172 BACKGROUND

• Gailani MR, Stahle-Backdahl M, Leffell DJ, Glynn M, Zaphiropoulos PG, Pressman C, Unden AB, Dean M, Brash DE, Bale AE, Toftgard R. The role of the human homologue of Drosophila patched in sporadic basal cell carcinomas. Nat Genet. 1996 Sep;14(1):78-81. doi: 10.1038/ng0996-78.

  PMID: 8782823 BACKGROUND

• Von Hoff DD, LoRusso PM, Rudin CM, Reddy JC, Yauch RL, Tibes R, Weiss GJ, Borad MJ, Hann CL, Brahmer JR, Mackey HM, Lum BL, Darbonne WC, Marsters JC Jr, de Sauvage FJ, Low JA. Inhibition of the hedgehog pathway in advanced basal-cell carcinoma. N Engl J Med. 2009 Sep 17;361(12):1164-72. doi: 10.1056/NEJMoa0905360. Epub 2009 Sep 2.

  PMID: 19726763 BACKGROUND

• Telfer NR, Colver GB, Morton CA; British Association of Dermatologists. Guidelines for the management of basal cell carcinoma. Br J Dermatol. 2008 Jul;159(1):35-48. doi: 10.1111/j.1365-2133.2008.08666.x.

  PMID: 18593385 BACKGROUND

• 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 BACKGROUND

• Chang AL, Solomon JA, Hainsworth JD, Goldberg L, McKenna E, Day BM, Chen DM, Weiss GJ. Expanded access study of patients with advanced basal cell carcinoma treated with the Hedgehog pathway inhibitor, vismodegib. J Am Acad Dermatol. 2014 Jan;70(1):60-9. doi: 10.1016/j.jaad.2013.09.012. Epub 2013 Nov 1.

  PMID: 24189279 BACKGROUND

• 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.

  PMID: 22670904 BACKGROUND

• Strasswimmer JM. Potential Synergy of Radiation Therapy With Vismodegib for Basal Cell Carcinoma. JAMA Dermatol. 2015 Sep;151(9):925-6. doi: 10.1001/jamadermatol.2015.0977. No abstract available.

  PMID: 25874820 BACKGROUND

• Pollom EL, Bui TT, Chang AL, Colevas AD, Hara WY. Concurrent Vismodegib and Radiotherapy for Recurrent, Advanced Basal Cell Carcinoma. JAMA Dermatol. 2015 Sep;151(9):998-1001. doi: 10.1001/jamadermatol.2015.0326.

  PMID: 25874733 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Basal Cell

Interventions

HhAntag691; Radiotherapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Armando Santoro, MD

  Istituto Clinico Humanitas

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: July 20, 2016
• First Posted: November 7, 2016
• Study Start: October 1, 2016
• Primary Completion: February 1, 2019
• Study Completion: January 1, 2020
• Last Updated: January 29, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)