Single-institution, single-arm, open-label phase II basket study of mutation and/or elevated hedgehog (Hh) expression-directed smoothened inhibitor sonidegib in patients with advanced solid malignancies

ACTRN 12623001216606

Brief Summary

The purpose of the study is to investigate whether Sonidegib (an anti-cancer drug) is effective and safe to use in patients with advancedat a late stage, far along solid organ cancers that have a specific SMO/PTCH1 gene mutation or elevated Hedgehog protein levels.

Intervention/Treatment

• Drug: Sonidegib

Inclusion Criteria

Part 1 – Biomarker Screeningtesting for cancer or conditions that can lead to cancer before symptoms appear, also known as cancer screening:

1. Advanced solid organ malignancy, with the exception of basal cell carcinomacancer arising from tissues that line organs.
2. Equal to or more than 18 years old.
3. ECOG 2 or less.
4. At least 1 line of prior systemic therapy (on active treatment allowed).
5. RECIST v1.1 measurable disease.
6. Archival tissuea group of cells that work together to perform a function (FFPE, core biopsyremoval of a section of tissue to analyse for cancer cells or unstained slides) for NGS and Hh expression testing.
7. Signed consent to screen for NGS and elevated Hh expression (bloodthe red bodily fluid that transports oxygen and other nutrients around the body and tissue).

Part 2 – Interventional Study (following fulfilment of criteria specified for part 1, further inclusion criteria for treatment with Sonidegib):

1. Presence of tumoura tissue mass that forms from groups of unhealthy cells SMO/PTCH1 mutation, or elevated tissue or serum Hh expression found through screening, or pre-identified on prior commercial NGS panel.
2. At least one line of prior systemic therapy (where standard of care systemic therapy exists).
3. Radiologic confirmed measurable disease as per RECIST Version 1.1 (confirmed equal to or more than 28 days prior to enrollment).
4. Prior palliative radiotherapy is permissible if completed equal to or more than 14 days prior to Sonidegib treatment to areas which are not included in response assessment.
5. Adequate bone marrowsoft, spongy tissue found in bones that makes blood cells function (e.g. plateletssmall disc-shaped blood cells that clump together to form clots to stop bleeding more than 100 x 109/L, ANC equal to or more than 1.5 x 109/L, Hb equal to or more than 90).
6. Adequate renal function (e.g. creatinine clearance equal to or more than 50 ml/min, serum creatinine less than or equal to 1.5 x ULN).
7. Adequate liver function (e.g. ALT/AST equal or less than 3 x ULN or equal to or less than 5 x ULN if liver metastases are present, bilirubin equal to or less than 2 x ULN).
8. Adequate cardiac function (e.g ECG and echocardiograma type of ultrasound that uses sound waves to create detailed images of the heart to assess heart structure, function and blood flow if clinically indicated).
9. Study treatment both planned and able to start within 28 days of confirmation of SMO or PTCH1a type of tumour supressor gene involved in the formation of tissues and organs, cell growth and cell division during embryonic development mutation, or elevated hedgehog expression.
10. Signed, written informed consenta process in which a patient receives detailed information about a procedure or treatment, including its potential risks, benefits, and alternatives. The patient then has the opportunity to understand the information and voluntarily agree to the procedure or treatment. (for trial inclusion and tissue collection).
11. Prior, part 2, screen failure patients are eligible for re-screening for Part 2.