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. 2015 Feb 9;17:e5. doi: 10.1017/erm.2015.3

Table 1.

Selected clinical trials of SMO inhibitors in cancer

SMO inhibitor Phase Indication Statusa Adverse events Dose/efficacy NCT # identifierb
Vismodegib (GDC-0449) 1 Locally advanced or metastatic solid tumours (= 68) Completed Frequent grade 1/2 AEs: muscle spasms, dysgeusia, fatigue, alopecia, nausea, decreased appetite, diarrhoea; grade 3/4 AEs occurred in 37% of patients Recommended phase 2 dose: 150 mg/day; ORR: 29% (58% in BCC, 1 unconfirmed response in MB) (Ref. 246) NCT00607724
1 Recurrent or refractory childhood MB Completed Recommended dose: 150–300 mg (Ref. 251) NCT00822458
1 High-risk first remission or relapsed multiple myeloma Ongoing NCT01330173
2 Recurrent of refractory adult MB Ongoing NCT00939484
2 Locally advanced or metastatic BCC (= 96) Ongoing Frequent grade 1/2 AEs (>30% of patients): muscle spasms, alopecia, dysgeusia, weight loss, fatigue; grade 3/4 AEs were reported in 25% patients Response rate: 43% for locally advanced BCC; 30% for metastatic BCC (Ref. 247) NCT00833417
2 Ovarian cancer in second or third remission (= 104) Completed Common grade 1/2 AEs: dysgeusia, ageusia, muscle spasms, alopecia; grade 3/4 AEs occurred in 23% (vismodegib) and 11.5% (placebo) of patients Median PFS: vismodegib 7.5 months compared with placebo 5.8 months (Ref. 249) NCT00739661
2 BCNS (= 41) Ongoing Frequent AEs: dysgeusia, muscle cramps, alopecia, weight loss Per patient rate of newly formed BCCs: 2 in vismodegib, 29 in placebo (Ref. 244) NCT00957229
2 Advanced chondrosarcoma Ongoing Common grade 1/2 AEs: myalgia, dysgeusia and alopecia; 2 patients had reversible grade 3/4 ALT or AST increase Clinical benefit rate: 26%; median PFS: 3.5 months; median OS: 12.4 months (Ref. 250) NCT01267955
Sonidegib (LDE-225) 1 Advanced solid tumours, including MB and BCC (= 103) Completed Common grade 1/2 AEs: muscle spasms, myalgia, gastrointestinal toxicities, increased liver enzymes, dysgeusia, fatigue, alopecia MTD: 800 mg/day; DLT: reversible grade 3–4 elevated serum creatine kinase (Ref. 248) NCT00880308
1/2 Advanced solid tumours in children, including MB Ongoing NCT01125800
2 Relapsed/refractory acute leukaemia Ongoing NCT01826214
2 ER/HER2-breast cancer Recruiting NCT01757327
BMS-833923 1 Solid tumours Completed NCT01413906
1 Advanced or metastatic solid tumours, including BCC and BCNS Completed NCT00670189
PF-04449913 1 Advanced solid tumours (= 23) Completed Frequent grade 1/2 AEs: dysgeusia, fatigue, decrease appetite, nausea, dizziness, dehydration, diarrhoea Recommended dose: 80–320 mg/day (Ref. 300) NCT01286467
1 Haematologic malignancies Completed NCT00953758
LY2940680 1 Advanced solid tumours Ongoing NCT01226485

Abbreviations: AEs, adverse events; ALT, alanine transaminase; AST, aspartate transaminase; BCC, basal cell carcinoma; BCNS, basal cell nevus syndrome; DLT, dose-limiting toxicity; ER, oestrogen receptor; HER2, human epidermal growth factor receptor 2; MB, medulloblastoma; MTD, maximum tolerated dose; ORR, overall response rate; OS, overall survival; PFS, progression free survival.

aStatus assessed on December 10th 2014; all ongoing trials are not recruiting.

bNCT # Identifier at http://clinicaltrials.gov.