An International, Randomized, Double-Blinded, Phase 3 Efficacy Study of XL184 versus Placebo in Subjects with Unresectable, Locally Advanced, or Metastatic Medullary Thyroid Cancer - ND

INTERVENTION: Product Code: XL184 Pharmaceutical Form: Capsule, hard Current Sponsor code: XL184 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 25‐ Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use Product Code: XL184 Pharmaceutical Form: Capsule, hard Current Sponsor code: XL184 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100‐ Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use CONDITION: Unresectable, Locally Advanced, or Metastatic Medullary Thyroid Cancer ; MedDRA version: 9.1 Level: LLT Classification code 10055107 Term: Thyroid cancer metastatic PRIMARY OUTCOME: Main Objective: To evaluate progression‐free survival (PFS) with XL184 treatment as compared with placebo in subjects with unresectable, locally advanced, or metastatic medullary thyroid cancer (MTC) Primary end point(s): the comparison of progression‐free survival (PFS) in subjects treated with XL184 versus placebo. Secondary Objective: To evaluate overall survival (OS) with XL184 treatment as compared with placebo To evaluate the objective response rate (ORR) and duration of response in subjects with measurable disease with XL184 treatment as compared with placebo, as per modified Response Evaluation Criteria In Solid Tumors (mRECIST) To evaluate changes in serum levels of calcitonin and carcinoembryonic antigen (CEA) as prognostic biomarkers for XL184 treatment benefit as compared with placebo To assess the potential relationship between RET germline and/or tumor DNA sequence alteration and the efficacy of XL184 To assess the pharmacodynamic effects of XL184 To evaluate the safety and tolerability of XL184 treatment To assess the pharmacokinetics (PK) of XL184 INCLUSION CRITERIA: 1. The subject has a histologically confirmed diagnosis of MTC that is unresectable, locally advanced, or metastatic, and disease that is measurable or non‐measurable per mRECIST. 2. The subject is at least 18 years old. 3. The subject has an ECOG (Eastern Cooperative Oncology Group) performance status ≤ 2. 4. The subject has documented progressive disease (PD) on computerized tomography (CT), magnetic resonance imaging (MRI) bone scan, or X‐ray (confirmed by the blinded central independent review committee [IRC]) per mRECIST at screening compared with a previous image done within 14 months of screening. 5. The subject has at least 10 unstained, consecutive slides of one archival tumor block or paraffin block, or a fresh tumor biopsy will be identified by the investigator for shipment to the central lab. The subject may be enrolled without providing slides if the site can provide the Sponsor with documentation of a germline mutation in RET in t