MoST Addendum 4 (substudy 9): This phase II study aims to assess the effectiveness of vismodegib, an oral cancer drug, in people with advanced or metastatic solid cancer with PTCH1 or SMO mutationsSingle arm, open label, signal seeking, phase IIa trial of the activity of vismodegib in patients with tumours harbouring PTCH1 or SMO mutations

Inclusion

1. Adults, aged 18 years and older, with pathologically confirmed advanced and/or metastatic solid cancer of any histologic type or an earlier diagnosis of a poor prognosis cancer, identified through the MoST molecular screening program.
2. Subjects with tumours with germline, or somatic Hedgehog pathway mutations in PTCH1 or SMO, excluding mutations in SMO known to affect vismodegib binding (ie. SMO G497W, SMO D473Y).
3. Confirmation of molecular eligibility by the molecular tumour board.
4. ECOG performance status 0, 1 or 2.
5. Received and failed all standard anticancer therapy or have documented unsuitability for any further standard therapy, if standard therapy exists.
6. Clinical or radiological progression on or following last anticancer therapy unless such anticancer therapy stopped due to toxicity / treatment intolerance.
7. Measurable disease as assessed by RECIST 1.1 or RANO.
8. Adequate organ system function as assessed by the following minimal laboratory requirements:
a. bone marrow function; platelets equal or greater than 100 x 10^9/L, ANC equal or greater than 1.5 x 10^9/L, and haemoglobin equal or greater than 9g/dL (5.6mmol/L);
b. liver function; ALT/AST equal or less than 3 x ULN (in the absence of liver metastases, equal or less than 5 x ULN for patients with liver involvement) and total bilirubin equal or less than 1.5xULN;
c. renal function; serum creatinine equal or less than 1.5xULN;
9. Willing and able to comply with all study requirements, including treatment (including ability to swallow whole capsules intact, without chewing, crushing, or opening the capsules), timing and/or nature of required assessments
10. Signed, written informed consent to participation in the specific treatment substudy.