To evaluate PFS with XL184 treatment as compared with placebo in subjects with unresectable, locally advanced, or metastatic MTC to see if the investigational drug XL184 is effective in delaying the growth of the tumor.
ID
Source
Brief title
Condition
- Endocrine neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary efficacy analysis in this study is the comparison of
progression-free survival (PFS) in subjects treated with XL184 versus placebo.
For the primary endpoint, PFS is defined as time from randomization to PD per
mRECIST as determined by a independent committee or death from any cause if
earlier.
Secondary outcome
The two key secondary endpoints are: Objective Response Rate (ORR) and Overall
Survival (OS).
Background summary
Thyroid cancer is the most common endocrine malignancy. Medullary Thyroid
Cancer (MTC) is an aggressive form of thyroid cancer with 10-year survival
rates of 40-50 % for subjects wit metastatic disease. Currently available
therapies for MTC are not curative and no large scale or phase-3 study has been
conducted. There is a clear need for novel therapeutics in the treatment of
MTC. XL184 is a new chemical entity that inhibits growth and angiogenic aspects
of the tumor.
Study objective
To evaluate PFS with XL184 treatment as compared with placebo in subjects with
unresectable, locally advanced, or metastatic MTC to see if the investigational
drug XL184 is effective in delaying the growth of the tumor.
Study design
The study consists of 3 periods:
1) Screening - screening procedures will be performed within a period of 28 days
2) Treatment - Patients will receive a daily dose of 175mg XL184 in 4-week
cycli. During the first 2 cycles, the patient will visit the hospital 5 times
for evaluation and every 4 weeks starting with cycle 3. A tumor assessment will
be performed once every 12 weeks. Treatment will continue until disease
progression.
3) Post- Treatment - Patient will return to the study site 30 days after the
last dose of study treatment. Follow-up information will be obtained every 12
weeks.
Intervention
Study treatment will be administered orally at a dose of 175 mg XL184 or
placebo once daily in 4-week cycles. Hematology and serum chemistry laboratory
evaluations and assessments of vital signs will be conducted every 2 weeks
during Cycles 1 and 2, and every 4 weeks starting with Cycle 3.Tumor
assessments will be performed every 12 weeks from randomization until PD as
determined by the investigator per mRECIST
Study burden and risks
Side effects reported related to treatment with XL184 and experienced by at
least:
* 20% of the subjects: Fatigue, diarrhea, loss of appetite, nausea,
constipation, vomiting, elevated blood pressure, hoarseness of the voice,
blisters, rash or pain in hands or feet.
* 5-20% of the subjects: changes in liver function which may indicate liver
damage, headache, shortness of breath, weight loss, abdominal pain, changes to
the way things taste or dry mouth, mouth sores / swelling or pain, increased
amylase or lipase values, dry skin, infection, back pain, heartburt, loss of
hair color or skin color, dizziness, insomnia, confusion, swelling of the hands
/ legs / feet, dehydration, increased levels of protein in the urine, seizure,
decreased amounts of potassium / magnesium / phosphorus / platelet counts /
sodium, urinary tract infection, depression, difficulty remembering things,
anxiety, blood clots, anemia, joint or muscle pain, bloody nose, increase
levels of glucose, difficulty swallowing, difficulty walking normally, fever,
flatulence, upper respiratory tract infection, hemorrhoids, muscle spams, itchy
skin.
210 East Grand Avenue
CA 94083, San Francisco
US
210 East Grand Avenue
CA 94083, San Francisco
US
Listed location countries
Age
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 (determined by the investigator) per mRECIST at screening compared with a previous image done within 14 months of screening.
5. The subject has recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0 Grade <= 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 >= 1500/mm3, platelets >= 100,000/mm3, hemoglobin >= 9 g/dL, bilirubin <= 1.5 times the upper limit of normal (does not apply to subjects with Gilbert*s syndrome), serum creatinine <= 1.5 mg/dL, and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 2.5 times the upper limit of normal.
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 >= 25 % 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 >= 4 weeks prior to randomization and stable without steroid and without anti-convulsant treatment for >= 10 days.
6. The subject has a history of clinically significant hematemesis or a recent history of hemoptysis of > 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 >= 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 > 140 mmHg systolic or > 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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2008-002320-29-NL |
| ClinicalTrials.gov | NCT00704730 |
| CCMO | NL25520.042.08 |