Study of two different doses of cabozantinib in progressive, metastatic medullary thyroid cancer
- Conditions
- Progressive Metastatic Medullary Thyroid CancerMedDRA version: 21.1 Level: PT Classification code 10027105 Term: Medullary thyroid cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2013-003402-40-HR
- Lead Sponsor
- Exelixis, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 250
1. The subject has a histologically confirmed diagnosis of MTC.
2. Availability of tumor tissue for shipment to the central laboratory according to prior determination of RET mutation status:
a. For subjects lacking evidence of a RET or RAS mutation, a recent tumor tissue sample will be required. Tissue shall come from a progressive tumor location, preferably from the most recently progressed metastatic site if feasible. If a recent tumor sample is not available, a tumor biopsy will be obtained during screening.
b. Subjects with documentation of a RET or RAS mutation found in tumor tissue will not be required to submit a recent tumor tissue sample; however, the report demonstrating the subject’s RET or RAS mutation must be reviewed and approved by the sponsor prior to subject randomization.
c. For subjects with documentation of a hereditary RET mutation, a tumor sample will not be required. Review and approval of the RET mutation report by the sponsor is required prior to randomization of the subject.
3. The subject has MTC that is metastatic as determined by the investigator based upon computerized tomography (CT), magnetic resonance imaging (MRI), bone scan, PET scan, or X-ray taken within 28 days before randomization.
4. The subject has disease that is measurable per RECIST 1.1 as determined by the investigator based upon CT or MRI images taken within 28 days before randomization.
5. The subject has documented progressive disease (PD) on CT, MRI, PET scan, bone scan, or X-ray as determined by the investigator per RECIST 1.1 on qualifying images taken within 4 months prior to randomization as compared to previous images taken within 14 months before the qualifying screening images.
a. PET scan can only be used to establish PD by the presence of new lesions (not to document increases in target or non-target lesions).
b. Bone scan or x-ray, can only be used to establish PD by the presence of new lesions in bone (not to document increases in target or non-target lesions).
6. The subject has recovered to baseline or CTCAE v4.0 = Grade 1 from toxicities related to any prior treatments, unless AE(s) are clinically non-significant and/or stable on supportive therapy.
7. The subject is = 18 years old on the day of consent.
8. The subject has an ECOG (Eastern Cooperative Oncology Group) status = 1 at screening
9. The subject has adequate organ and marrow function, based upon the following laboratory criteria from assessments performed within 28 days before randomization
a. Absolute neutrophil count (ANC) = 1500/mm3
b. Platelets = 100,000/mm3
c. Hemoglobin = 9 g/dL
d. Total bilirubin = 1.5 x the upper limit of normal (ULN). For subjects with known Gilbert’s disease, total bilirubin = 3.0 mg/dL.
e. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3.0 x ULN
f. Serum creatinine = 1.5 x ULN or creatinine clearance = 50 mL/min (using the Cockcroft-Gault equation: CrCl (mL/min) = (140 – age) x wt (kg) / (serum creatinine [mg/dL] x 72); for females multiply by 0.85
g. Urine protein/creatinine ratio (UPCR) = 1 mg/mg (= 113.1 mg/mmol) or 24-hour urine protein < 1 g
1. The subject has previously received cabozantinib
2. The subject has received prior treatment with a small molecule kinase inhibitor or a hormonal therapy within 28 days or five half-lives of the compound or active metabolites, whichever is shorter before randomization or at any time after the date of the qualifying images used to document PD for eligibility
3. The subject has received prior systemic anti-tumor therapy within 28 days of randomization or at any time after the date of the qualifying images used to document PD for eligibility
4. The subject has received any other type of investigational agent within 28 days before randomization or at any time after the date of the qualifying images used to document PD for eligibility
5. The subject has received radiation therapy within 28 days or radionuclide treatment within 42 days of randomization. Subject is ineligible if there are any clinically relevant ongoing complications from prior radiation therapy
6. The subject has untreated and/or active central nervous system (CNS) metastasis. Must have completed radiation therapy = 28 days prior to randomization and stable without corticosteroids or anti-convulsant treatment for = 10 days
7. Concomitant anticoagulation at therapeutic doses with oral anticoagulants or platelet inhibitors
8. The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
a. Cardiovascular disorders incl.
i. Symptomatic congestive heart failure, unstable angina pectoris, or serious cardiac arrhythmias
ii. Uncontrolled hypertension defined as sustained BP > 150 mm Hg systolic, or > 100 mm Hg diastolic despite optimal antihypertensive treatment
iii. Stroke, myocardial infarction, or other ischemic event within 6 months before randomization
iv. Thromboembolic event within 3 months before randomization.
b. Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:
i. Tumors invading the GI tract, active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction
ii. Abdominal fistula, GI perforation, bowel obstruction, intra-abdominal abscess within 6 months before randomization,
Note: Complete healing must be confirmed prior to randomization, including radiographic evidence of complete resolution of abdominal abscess
c. Major surgery within 2 months before randomization. Complete healing from major surgery must have occurred 1 month before randomization. Complete healing from minor surgery must have occurred at least 7 days before randomization. Subjects with clinically relevant complications from prior surgery are not eligible
d. Cavitating pulmonary lesion(s) or endobronchial disease
e. Lesion invading a major blood vessel
f. Clinically significant bleeding risk including the following within 3 months of randomization: hematuria, hematemesis, hemoptysis of >0.5 teaspoon (>2.5 mL) of red blood, or other signs indicati
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method