Health Condition 1: C73- Malignant neoplasm of thyroid gland
Conditions
Interventions
Intervention1: Dabrafenib (DRB436): 150 mg twice daily.
oral administration,
Patients will receive dabrafenib in combination with trametinib or placebo until disease progression as per RECIST 1.1 as
Sponsors
Novartis Healthcare Pvt Ltd
Eligibility
Inclusion criteria
Inclusion criteria: 1 Signed informed consent must be obtained prior to performing any protocol specific pre-screening and screening procedure. 2 Male or female>= 18 years of age at time of informed consent. 3 Histologically or cytologically confirmed diagnosis of advanced/metastatic differentiated thyroid carcinoma. 4 Radioactive-iodine refractory disease 5 BRAFV600E mutation-positive tumor sample as per Novartis-designated central laboratory result 6 Has progressed on at least 1 but not more than 2 prior VEGFR targeted therapy 7 Eastern Cooperative Oncology Group (ECOG) performance status 8 At least one measurable lesion as defined by RECIST v1.1.
Exclusion criteria
Exclusion criteria: 1 Anaplastic or medullary carcinoma of the thyroid. 2 Previous treatment with a BRAF inhibitor and/or a MEK inhibitor. 3 Concomitant RET Fusion-Positive Thyroid Cancer. 4 Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before randomization. 5 Receipt of any type of anticancer antibody (including investigational antibody) or systemic chemotherapy within 4 weeks before randomization. 6 Receipt of radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before randomization. 7 A history or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To compare PFS between dabrafenib plus trametinib versus placebo.Timepoint: PFS based on BIRC assessment using RECIST 1.1 criteria | — |
Secondary
| Measure | Time frame |
|---|---|
| â?¢ to compare ORR of dabrafenib plus trametinib versus placebo â?¢ to compare OS of dabrafenib plus trametinib versus placebo Timepoint: â?¢ ORR as per BIRC assessment using RECIST 1.1 criteria â?¢ OS including all deaths from any cause ;â?¢ to evaluate DoR of dabrafenib plus trametinib versus placeboTimepoint: â?¢ DoR by BIRC assessment using RECIST v1.1 criteria;â?¢ To characterize the safety and tolerability of dabrafenib and trametinibTimepoint: â?¢ Incidence and severity of AEs and SAEs, including changes in laboratory values, ECOG PS (performance status), and vital signs.;â?¢ To quantify trametinib associated serous retinopathy ocular eventsTimepoint: â?¢ Incidence, type and severity of trametinib associated serous retinopathy ocular events. | — |
Countries
Argentina, Brazil, Canada, China, India, Japan, Malaysia, Mexico, Republic of Korea, Russian Federation, South Africa, Taiwan, Turkey, United States of America, Viet Nam
Contacts
Public ContactMurugananthan K
Novartis Healthcare PVT LTD
Outcome results
None listed