Date: 2011-06-20
Type of information:
phase: 2
Announcement: results
Company: Roche (Switzerland)
Product: vismodegib (RG3616/GDC-0449)
Action mechanism: Vismodegib is an investigational medicine designed to target the underlying molecular driver of basal cell carcinoma. Abnormal signalling in a cell growth pathway, known as the Hedgehog pathway, is implicated in more than 90 percent of basal cell carcinoma cases and vismodegib is designed to selectively inhibit abnormal signaling in the Hedgehog pathway.
Disease: advanced basal cell carcinoma
Therapeutic area: Cancer - Oncology
Country: Australia, Europe, USA
Trial details: ERIVANCE BCC is an international, single-arm, multi-centre, two-cohort, open-label Phase II study that enrolled 104 patients with advanced basal cell carcinoma, including la basal cell carcinoma (71) and m basal cell carcinoma (33). la basal cell carcinoma patients had lesions that were inappropriate for surgery (inoperable, or for whom surgery would result in substantial deformity) and for which radiotherapy was unsuccessful or contraindicated. m basal cell carcinoma was defined as basal cell carcinoma that had spread to other parts of the body, including the lymph nodes, lung, bones and/or internal organs. The 31 study sites were located in the US, Australia and Europe. Study participants received 150mg vismodegib orally, once daily until disease progression or intolerable toxicity.
Latest
news: Roche has announced that a pivotal Phase II study with vismodegib showed positive results in people with advanced basal cell carcinoma (BCC) for whom surgery is considered inappropriate. Basal Cell Carcinoma is a form of skin cancer that can cause disfiguring and debilitating effects and can ultimately be life-threatening. Vismodegib is an investigational, oral medicine designed to selectively inhibit signalling in the Hedgehog pathway, which is implicated in more than 90 percent of BCC cases.
The trial showed vismodegib substantially shrank tumours or healed visible lesions (overall response rate) in 43 percent of patients with locally advanced basal cell carcinoma (laBCC) and 30 percent of patients with metastatic basal cell carcinoma (mBCC), as assessed by independent review, the primary endpoint. The most common drug related adverse events were muscle spasms, hair loss, altered taste sensation, weight loss, fatigue, nausea, decreased appetite and diarrhoea.
The primary endpoint of the trial showed an overall response rate of 43 percent in the laBCC cohort, and 30 percent in mBCC, as assessed by independent review. Study investigators assessed the overall response rate for laBCC and mBCC at 60 percent and 46 percent, respectively (secondary endpoint). The median duration of progression-free survival (PFS) by independent review for both metastatic and locally advanced BCC patients was 9.5 months.
In addition, the clinical benefit rate (defined as patients who experienced response as well as those who experienced prolonged stable disease for more than 24 weeks) showed vismodegib shrank tumours or healed visible lesions, or prevented them from growing any further in 75 percent of patients, as assessed by independent review.
The most common adverse events included muscle spasms, hair loss, altered taste sensation, weight loss, fatigue, nausea, decreased appetite and diarrhoea. Serious adverse events (SAEs) were observed in 26 patients (25 percent), however of these only four (4 percent) patients had SAEs that were considered to be related to treatment with vismodegib. Fatal events were reported in seven patients (7 percent); none were considered by investigators to be related to treatment with vismodegib. In all cases, patients had other pre-existing diseases or symptoms that were related to their presumed cause of death.
In order to provide people with advanced BCC (who are appropriate candidates) access to vismodegib while Roche discusses next steps with the European Medicines Agency, the company is conducting a phase II safety study in the EU and other countries.
