Metastatic or unresectable papillary thyroid cancer
Conditions
Interventions
Patients receive oral OR5185426 of 960mg b.i.d. daily.
Sponsors
Hoffmann-La Roche
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Male or female patients >= 18 years of age 2. Histologically confirmed papillary thyroid cancer that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective.Patients whose tumors exhibit areas of *other histology* may be enrolled, provided the tumor histology remains predominantly papillary. Patients whose tumors exhibit *mixed* histology may be discussed with the Medical Monitor if there are questions about eligibility. 3. BRAFV600-positive thyroid cancer tissue, as determined by the Roche-designated Central Reference Laboratory using the cobas® 4800 BRAF V600 Mutation Test. Testing requires a formalin-fixed paraffin-embedded (FFPE) tumor tissue block or unstained sections from such a block. Samples may be either archival or new. Fine needle and core needle biopsies will not be accepted. 4. Must have radioactive iodine resistant disease, defined by any one of the following: o lack of RAI uptake on either a low-dose diagnostic or a post-therapy RAI scan in the measurable lesion (or lesions) demonstrated previously (without time limitation), or o radiographic progression of disease within 18 months of last course of RAI therapy despite the presence of RAI uptake on the scans performed with that prior therapy, or o Patient that has exceeded a cumulative activity of at least 600 mCi of radioiodine therapy 5. Thyroid carcinoma tissue, either archival or recent biopsy must be available for submission and review by a central pathology laboratory. 6. Allowed Prior therapy: - Cohort 1: may have received surgery, RAI, and/or standard of care chemotherapy (e.g. doxorubicin) [Note: Acceptable prior chemotherapy can be discussed with the Sponsor.] Cohort 2: may have received surgery, RAI, and standard of care chemotherapy (e.g. doxorubicin), and must also have received prior treatment with investigational or commercial tyrosine kinase inhibitor with activity against VEGFR2 provided the drug is not a specific/selective BRAF or MEK pathway inhibitor. [Note: Acceptable prior chemotherapy can be discussed with the Sponsor.] 7. Must have fully recovered from the effects of any previous therapies. 8. Radiologic (CT or MRI) evidence of clinically relevant disease progression (as per RECIST 1.1) within the preceding 14 months prior to planned first treatment. 9. Measurable disease (by RECIST Version 1.1 criteria) 10. ECOG performance status of 0 or 1 11. Life expectancy > 3 months 12. Be able to swallow pills 13. Must have a head CT/MRI to evaluate for CNS metastasis within 28 days prior to study drug treatment (Cycle 1 Day 1). Patients with radiographically stable, asymptomatic previously treated lesions are eligible provided: o Patient has received prior treatment (including radiation), stereotactic radiosurgery, surgical resection) to the site(s) of CNS metastatic disease >= 28 days prior to starting study treatment o Patient has no requirement for glucocorticoids, and discontinued >= 21 days prior to starting study treatment) o Patient is not taking anticonvulsants (discontinued at least 3 weeks prior to treatment) o Patient has no overt evidence of neurological deficit 14. Prior Surgery (excluding tumor biopsy at baseline for biomarker analysis) must have occurred at least 14 days
Exclusion criteria
Exclusion criteria: 1. Histological diagnosis other than papillary thyroid carcinoma (PTC), including squamous cell variants of PTC or PTC with areas of squamous metaplasia.Patients with anaplastic tumors are not eligible. However, patients whose tumors contain areas of *un-differentiated* or *de-differentiated* histology may enroll provided the original diagnosis was clearly PTC, and the tumor histology remains predominantly papillary at enrollment. Patients whose tumors exhibit mixed histology may be discussed with the Medical Monitor. 2. Active or untreated CNS metastases 3. History of or known carcinomatous meningitis 4. Anticipated or ongoing administration of any anti-cancer therapies other than those administered in this study 5. Active squamous cell skin cancer that has not been excised or has not yet adequately healed post excision 6. Pregnant or lactating women 7. Previous treatments with any commercial or investigational targeted agents that specifically and selectively targets the MEK or BRAF pathway 8. Received any investigational treatment within 28 days prior to start of study treatment 9. Prior radioactive iodine therapy within 28 days prior to start of study treatment 10. Chemotherapy or targeted therapy (in case of cohort 2) within 28 days prior to start of study treatment 11. Prior radiotherapy to the only measurable lesion 12. Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate absorption 13. QTc >450 msec on screening ECG or history of congenital long QT syndrome or uncorrectable electrolytes abnormalities.At least one QTc measurement using Fridericia*s correction (QTcF) must be 450 msec may be discussed with the Medical Monitor for potential inclusion. 14. NCI CTCAE Version 4.0 grade 3 hemorrhage within 28 days of starting the study treatment 15. Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or active pulmonary embolism 16. Known clinically significant active infection at the time of study treatment start 17. History of allogeneic bone marrow transplantation or organ transplantation 18. Other severe, acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, which in the judgment of the investigator would make the patient inappropriate for entry into this study 19. Patients with a previous malignancy are excluded except for patients with adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer and/or curatively treated cancer, from which the patient is currently disease-free, or any malignancy from which the patient has been continuously disease-free for at least 5 years. Also, isolated elevation in PSA in the absence of prostate cancer is allowed 20. Known HIV positivity or AIDS-related illness, HBV, and active HCV
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary efficacy variable for this study is the rate of best overall response (BORR) assessed by the investigators according to the RECIST criteria (Version. 1.1). | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary efficacy variables are: Clinical benefit rate (CBR), PFS, OS, and duration of response, in TKI-naïve patients (Cohort 1) TKI-exposed patients (Cohort 2). | — |
Countries
Netherlands
Outcome results
None listed