Health Condition 1: null- Medullary Thyroid Cancer.
Conditions
Interventions
Intervention1: 1.Experimental - Drug: XL184: Gelatin capsules supplied in 25-mg and 100-mg strengths administered orally daily
Control Intervention1: 2.Placebo Comparator - Drug: Placebo: Gelatin cap
Sponsors
Exelixis Inc
PPD Pharmaceutical Development India Pvt Ltd
Eligibility
Inclusion criteria
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. In addition, and in India only, the subject does not exceed 65 years of age at the time of randomization. 3. The subject has an ECOG (Eastern Cooperative Oncology Group)performance status less than or equal to 2. 4. The subject has documented progressive disease (PD) on computerized tomography (CT), magnetic resonance imaging (MRI), bone scan, or X-ray (determined by the investigator) per mRECIST at screening compared with a previous image done within 14 months of screening (see Section 5.13.1.1). 5. The subject has recovered to National Cancer Institute (NCI)Common Terminology Criteria for Adverse Events (CTCAE) v3.0 Grade less than or equal to 1 from clinically significant adverse events (AEs) due to antineoplastic agents, investigational drugs, or other medications that were administered prior to randomization. 6. The subject has organ and marrow function as follows: absolute neutrophil count more than or equal 1500/mm3, platelets more than or equal 100,000/mm3, hemoglobin more than or equal 9 g/dL, bilirubin less than or equal to 1.5 times the upper limit of normal (does not apply to subjects with Gilberts syndrome), serum creatinine less than or equal 1.5 mg/dL, and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal 2.5 times the upper limit of normal. 7. Sexually active subjects must agree to use medically accepted methods of contraception during the course of the study and for 3 months following discontinuation of study treatments (excluding women who are not of child bearing potential and men who have been sterilized). 8. The subject has no other diagnosis of malignancy (unless non-melanoma skin cancer, carcinoma in situ of the cervix, or a malignancy diagnosed more than or equal to 2 years previously) and currently has no evidence of malignancy (unless non-melanoma skin cancer or carcinoma in situ of the cervix). 9. Female subjects of childbearing potential must have a negative pregnancy test at screening. Females of childbearing potential are defined as sexually mature women without prior hysterectomy or who have had any evidence of menses in the past 12 months. However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, anti-estrogens, or ovarian suppression.
Exclusion criteria
Exclusion criteria: 1. The subject has received prior systemic anti-tumor therapy (eg, chemotherapy, biologic modifiers, or anti-angiogenic therapy)within 4 weeks of randomization (6 weeks for nitrosoureas or mitomycin C). 2. The subject has received radiation to more than or equal to 25 percent of bone marrow. 3. The subject has received treatment with other investigational agents within 4 weeks of randomization. 4. The subject has received treatment with XL184. 5. The subject has brain metastases or spinal cord compression, unless completed radiation therapy more than or equal 4 weeks prior to randomization and stable without steroid and without anti-convulsant treatment for more than or equal to 10 days. 6. The subject has a history of clinically significant hematemesis or a recent history of hemoptysis of more than 2.5 mL of red blood or other signs indicative of pulmonary hemorrhage or evidence of endobronchial lesion(s). 7. The subject has a urine protein/creatinine ratio of more than or equal to 1 (reported in grams of protein over grams of creatinine). 8. The subject has serious intercurrent illness, such as hypertension (two or more blood pressure readings performed at screening of more than 140 mmHg systolic or more than 90 mmHg diastolic) despite optimal treatment, unhealed wounds from recent surgery, or cardiac arrhythmias; or a recent history of serious disease such as either symptomatic congestive heart failure or unstable angina pectoris within the past 3 months, or myocardial infarction, stroke, or transient ischemic attack within the past 6 months. 9. The subject is pregnant or breastfeeding. 10. The subject has an active infection requiring systemic treatment. 11. The subject has a known allergy or hypersensitivity to any of the components of the XL184 or placebo formulations. 12. The subject is incapable of understanding and complying with the protocol or unable to provide informed consent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate progression-free survival (PFS) with XL184 as compared with placebo in subjects with unresectable, locally advanced, or metastatic medullary thyroid cancer (MTC)Timepoint: Assessed at periodic visits | — |
Secondary
| Measure | Time frame |
|---|---|
| To assess the pharmacokinetics and pharmacodynamic effects of XL184Timepoint: Assessed at periodic visits;To evaluate overall survival (OS) with XL184 as compared with placeboTimepoint: Assessed at periodic visits;To evaluate the objective response rate (ORR) and duration of response in subjects with measurable disease with XL184 as compared with placeboTimepoint: Assessed at periodic visits;To evaluate the safety and tolerability of XL184Timepoint: Assessed at periodic visits | — |
Countries
Austria, Belarus, Belgium, Brazil, Canada, Chile, Denmark, France, Germany, Greece, India, Israel, Italy, Netherlands, Peru, Poland, Portugal, Republic of Korea, Russian Federation, Saudi Arabia, Spain, Sweden, Switzerland, United Kingdom, United States of America
Contacts
Public ContactArun Sundriyal
PPD Pharmaceutical Development India Pvt. Ltd.
Outcome results
None listed