None listed
Conditions
Brief summary
This is a substudy of the Cancer Molecular Screening and Therapeutics (MoST) Program, which is registered on ANZCTR with ID ACTRN12616000908437. This substudy will evaluate the activity of vismodegib in patients with advanced cancers and tumours. Who is it for? You may be eligible to join the study if you are aged 18 years and older, with pathologically confirmed advanced and/or metastatic solid cancer of any cell type or an earlier diagnosis of a poor prognosis cancer and have received all standard anticancer therapy. Participants will have tumours with mutations in PTCH1 or SMO. Study details Participants will continue to consume one 150mg capsule of vismodegib for as long as they and their doctor agree there is a benefit from treatment. Participants will undergo imaging assessments at 8 weekly intervals or as clinically indicated in order to evaluate tumour response. Safety and tolerability of treatment and health related quality of life during treatment will be assessed at 4 weekly intervals. We cannot guarantee that patients will receive any benefits from this study. This study is being carried out to improve the way we treat cancer patients who may have limited treatment options available to them. It is hoped that vismodegib will be well tolerated and will improve outcomes for future patients, however, there may be no clear benefit from participation in this study.
Interventions
Vismodegib will be taken orally by the participant, at home, at a dose of 150 mg/day (1 capsule), Vismodegib will be taken continuously until disease progression is documented, the patient experiences intolerable toxicity or withdraws for another reason. Participants will be asked to return unused drug and empty drug containers at each return visit. The Pharmacy Department at participating institutions will maintain a record of drugs dispensed for each patient.
Sponsors
The University of Sydney
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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.
Exclusion criteria
1. Contraindications to investigational product. 2. Known history of hypersensitivity to active or inactive components of investigational product. 3. Previous treatment with the same agent or same class of agent. 4. Specific comorbidities or conditions (e.g. psychiatric) or concomitant medications which may interact with the investigational product(s). 5. Co-morbidities or conditions that may compromise assessment of key outcomes or in the opinion of the clinician, limit the ability of the patient to comply with the protocol. 6. Treatment with any of the following anti-cancer therapies prior to the first dose of study treatment: a. Radiation therapy, surgery or tumour embolization within 14 days prior to the first dose of study treatment. Palliative radiotherapy (for analgesia) is acceptable only if the irradiated field does not include target lesions; b. Immunotherapy within 28 days prior to the first dose of study treatment; c. Chemotherapy, biologic therapy, or hormonal therapy within 14 days or 5 half-lives of a drug prior to the first dose of study treatment or until recovery from previous therapy (whichever is longer); 7. Any unresolved toxicity (greater than CTCAE grade 2) from previous anti-cancer therapy. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripheral neuropathy). 8. Administration of any investigational treatment within 30 days or 5 half-lives (whichever is longer) prior to receiving the first dose of study treatment. 9. For non central nervous system (CNS) cancers, patients with symptomatic CNS involvement of his/her cancer are excluded. Subjects with stable neurological function, on stable doses of steroids/anti-epileptics over 4 weeks, and with no evidence of CNS progression within 12 weeks prior to screening are eligible. 10. History of another malignancy within 2 years prior to molecular screening registration are excluded unless adequately treated and determined free of progressive and metastatic disease for at least 6 months. Patients with a past history of adequately treated carcinoma-in-situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or superficial transitional cell carcinoma of the bladder can be included. 11. Pregnancy, lactation, or inadequate contraception per the vismodegib IB. Women must be post-menopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration. Men must have been surgically sterilised or use a (double if required) barrier method of contraception even after vasectomy during sexual intercourse with women while being treated with vismodegib 12. Subjects with Basal Cell Carcinoma (BCC) or melanoma 13. Tumours with SUFU mutations 14. Patients with one of the following rare hereditary conditions: galactose intolerance, primary hypolactasia, or glucose-galactose malabsorption 15. Prior treatment with a Hedgehog pathway inhibitor 16. Treatment with CYP and P-gp inhibitors or CYP inducers within 7 days of registration
Outcome results
None listed