An Open-Label, Multi-Center Phase II Study of the BRAF Inhibitor RO5185426 in Patients with Metastatic or Unresectable Papillary Thyroid Cancer (PTC) Positive for the BRAF V600 Mutation and Resistant to Radioactive Iodine (NO25530B)


Metastatic Thyroid Cancer | Unresectable Papillary Thyroid Cancer

Trial Phase

Trial Purpose and Description

Trial Purpose

This research study designed to look at whether the drug vemurafenib (also called Zelboraf or RO5185426) can help stop the growth and spread of cancer cells in patients with papillary thyroid cancer (PTC) which has spread to other parts of the body (is metastatic), cannot be removed by surgery (is unresectable), and was or has become resistant to radioactive iodine treatments. The study will also collect additional information about the safety of Vemurafenib Vemurafenib is approved by the U.S. Food and Drug Administration (FDA) for the treatment of late stage melanoma whose tumors show a gene mutation called BRAF V600. It is not approved for treatment of PTC so in this study the use of Vemurafenib is investigational, meaning that it is not approved for routine treatment for PTC and can only be used in PTC in research studies such as this one. Secondary purposes of the study include • whether vemurafenib may be of benefit to patients previously treated with sorafenib who have PTC • pharmacokinetics of vemurafenib (to see how long the study drug stays in your body and how well your body can get rid of the drug) • if treatment with vemurafenib will have an effect on proteins in your blood, tumor or skin that will provide information on how your tumor responds to treatment. These proteins are called ‘biomarkers.’ You must allow testing of your samples for biomarkers for at least 5 years in order to participate in this study. Exploring biomarkers are an important part of this study because we are trying to identify what the right treatment is for different types of patients. • evaluate the Roche Companion Diagnostics (coDx) cobas® 4800 BRAF V6000 Mutation Test (to detect the BRAF gene mutation) from tumor samples. The 4800 BRAF is FDA approved for detecting the BRAF mutation in metastatic melanoma but is investigational in this study

Participation Guidelines

18 Years and older

Eligibility Criteria

4.2.1 Inclusion Criteria
Patients are eligible to participate in this study if they meet all of the following 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.
NOTE: 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.
CONFIDENTIAL Roche Protocol NO25530D (RO5185426) - Page 61
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 prior to first dose of study treatment, and patients must have
recovered from any effects from surgery and have adequate wound healing prior to
first dose of study treatment.
15. External beam radiotherapy for the treatment of a symptomatic (e.g. bone) metastasis
as clinically indicated must be at least 14 days prior to first dose of study treatment
CONFIDENTIAL Roche Protocol NO25530D (RO5185426) - Page 62
16. Completed baseline skin exam by a dermatologist or other qualified physician for
cutaneous squamous cell carcinoma. Exam must be negative or if, suspected cuSCC,
basal cell carcinoma (BCC), or other suspicious lesions are identified they must be
excised, and there must be adequate wound healing prior to study treatment.
17. Thyroid stimulating hormone (TSH) level <;0.5 mIU/L
18. Adequate hematologic, renal and liver function
o Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
o Platelet count ≥ 100 x 109/L
o Hemoglobin ≥ 9 g/dL
o Serum creatinine ≤1.5 X ULN or CrCl >; 40 ml/hr by Cockcroft-Gault formula
o AST and ALT ≤ 2.5 times upper limit of normal (ULN) (≤ 5 times ULN for
patients with concurrent liver metastases)
o Bilirubin ≤ 1.5 times ULN
o Alkaline phosphatase ≤ 2.5 times ULN (≤ 5 times ULN for patients with
concurrent liver metastases)
19. Negative serum pregnancy test within 7 days prior to commencement of dosing in
pre-menopausal women. Women of non-childbearing (see Appendix 6) potential may
be included if they are either surgically sterile or have been postmenopausal
for ≥ 1 year
20. Fertile men and women must use an effective method of contraception during
treatment and for at least 6 months after completion of treatment as directed by their
physician (in accordance with local requirements)
21. Absence of any psychological, familial, sociological or geographical condition
potentially hampering compliance with the study protocol and follow-up schedule;
those conditions should be discussed with the patient before trial entry
22. Before study entry, signed informed consent must be obtained from patient prior to
performing any study-related procedures

Hoffmann-La Roche
December 2011
Last Updated:
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