Efficacy of XL184 (Cabozantinib) in Advanced Medullary Thyroid Cancer
- Registration Number
- NCT00704730
- Lead Sponsor
- Exelixis
- Brief Summary
The purpose of this research study is to evaluate the progression-free survival (PFS) with XL184 as compared with placebo (an inactive substance) in subjects with unresectable, locally advanced, or metastatic medullary thyroid cancer (MTC). Subjects will be randomized to receive XL184 or placebo in a 2:1 ratio. XL184 is an investigational drug that inhibits VEGFR2, MET and RET, kinases implicated in tumor formation, growth and migration.
The Clinical Steering Committee for this study, comprised of study doctors who specialize in medullary thyroid cancer, has provided guidance regarding the design of the study. The committee includes: Douglas Ball, MD, Barry Nelkin, PhD, Martin Schlumberger, MD and Steven Sherman, MD.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 330
- The subject has a histologically confirmed diagnosis of MTC that cannot be removed by surgery, is locally advanced, or has spread in the body.
- The subject is at least 18 years old.
- The subject has an ECOG (Eastern Cooperative Oncology Group) performance status ≤ 2.
- The subject has documented worsening of disease (progressive disease) at screening compared with a previous CT scan or MRI image done within 14 months of screening.
- The subject has recovered from clinically significant adverse events (side effects) due to any other medications that were administered prior to randomization.
- The subject has adequate organ and bone marrow function.
- Subjects who are sexually active (male and female) must agree to use medically accepted methods of contraception during the course of the study and for 3 months following discontinuation of study treatments.
- The subject has no other diagnosis of cancer (unless non-melanoma skin cancer, an early form of cervical cancer, or another cancer diagnosed ≥ 2 years previously) and currently has no evidence of malignancy (unless non-melanoma skin cancer or an early form of cervical cancer).
- Female subjects of childbearing potential must have a negative pregnancy test at screening.
- The subject has received prior treatment for their cancer within 4 weeks of randomization (6 weeks for nitrosoureas or mitomycin C).
- The subject has received radiation to ≥ 25 % of bone marrow.
- The subject has received treatment with other investigational agents (unapproved therapies) within 4 weeks of randomization.
- The subject has received treatment with XL184.
- 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.
- The subject has a history of clinically significant episodes of vomiting blood or a recent history of vomiting > 2.5 mL (about 1/2 teaspoon) of red blood.
- The subject has serious illness other than cancer.
- The subject is pregnant or breastfeeding.
- The subject has an active infection requiring ongoing treatment.
- The subject is incapable of understanding and complying with the protocol or unable to provide informed consent.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 1 XL184 - 2 Placebo -
- Primary Outcome Measures
Name Time Method Progression-Free Survival (PFS) Treatment period consisted of 4-week cycles with radiologic tumor assessment every 12 weeks from date of randomization until date of first documented PD or date of death from any cause, whichever came first, assessed up to 34 months. The duration of Progression-Free Survival (PFS) using progression events as determined by Independent Review Committee (IRC) per mRECIST, or death due to any cause. The analysis was conducted after at least 315 subjects were randomized and at least 138 events were observed.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) With XL184 Compared With Placebo The pre-specified interim analysis of Overall Survival (OS) was assessed at 44% of required events. Includes data up to 15June2011. As of this date, the number of deaths required to conduct the primary analysis had not been reached. Duration of Overall Survival (OS) from the time of randomization to death due to any cause. A Kaplan-Meier analysis was performed to estimate the median.
Objective Response Rate (ORR) Assessed at the same time as primary analysis of Progression Free Survival (PFS) data. Assessed at baseline and every 12 weeks until Progressive Disease (PD) up to 34 months. The proportion of subjects with a best overall response (BOR) of confirmed complete response (CR) or partial response (PR) as determined by the Independent Review Committee (IRC.) Per Response Evaluation Criteria in Solid Tumor Criteria (mRECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR) disappearance of all target lesions; Partial Response (PR) ≥ 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) ≥ 20% increase in the sum of the longest diameter of target lesions. Overall Response Rate: ORR=CR +PR
Duration of Objective Response (OR): Independent Radiology Committee (IRC) Determined From time of first documentation of Objective Response (OR), confirmed at a later visit ≥28 days later as Progressive Disease (PD) as defined by mRECIST or death due to any cause, assessed up to 34 months. For those subjects with Independent Radiology Committee (IRC) determined Objective Response Rate (ORR), the amount of time from documentation of Objective Response (OR) until Progressive Disease (PD) by mRECIST or death due to any cause.
Biochemical Response Carcinoembryonic Antigen (CEA) % Serum tumor markers CEA evaluated from blood samples collected at screening and every 12 weeks (± 5 days from randomization) until date of first documented progression or date of death from any cause, whichever came first, assessed for up to 34 months. For each on-treatment tumor marker assessment from each subject, the biochemical response of CEA was determined based on percent increase or decrease from baseline. Best biochemical response over the course of treatment was determined from evaluation of each subject's time point response data. Biochemical response: Complete Response (CR)- Decrease in tumor marker into normal range from baseline value; Partial Response (PR)- Decrease of \>50% from baseline value when baseline value is above normal range; Stable Disease (SD)- No more than a 50% increase and no more than a 50% decrease from baseline value above normal range; Progressive Disease (PD)- Increase of \>50% from baseline value when baseline value is above normal range / or increase from low or normal range at baseline to above normal range; Not Evaluable (NE)- Missing baseline value / or baseline value is not elevated and response is not Progressive Disease (PD) / or response can not be determined due to change in assay format.
Biochemical Response Calcitonin (CTN) % Serum tumor markers CTN evaluated from blood samples collected at screening and every 12 weeks (±5 days from randomization) until date of first documented progression or date of death from any cause, whichever came first, assessed for up to 34 months. For each on-treatment tumor marker assessment from each subject, the biochemical response of CTN was determined based on percent increase or decrease from baseline. Best biochemical response over course of treatment was determined from evaluation of subject's time point response data. Biochemical response criteria: Complete Response (CR) - decrease in tumor marker into normal range from baseline value; Partial Response (PR) - decrease of \>50% from baseline value when baseline value is above normal range; Stable Disease (SD) - no more than a 50% increase and no more than a 50% decrease from baseline value above normal range; Progressive Disease (PD) - increase of \>50% from baseline value when baseline value is above normal range / or increase from low or normal range at baseline to above normal range; Not Evaluable (NE) - missing baseline value / or baseline value is not elevated and response is not PD / or response can not be determined due to change in assay format.
Trial Locations
- Locations (49)
Indiana University Melvin and Bren Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
Ohio State University, James Cancer Hospital
🇺🇸Columbus, Ohio, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Hospital of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Kansas University Medical Center
🇺🇸Kansas City, Kansas, United States
CHUM - Hopital Saint-Luc
🇨🇦Montreal, Quebec, Canada
Universitair Ziekenhuis
🇧🇪Leuven, Belgium
Washington Cancer Institute
🇺🇸Washington, District of Columbia, United States
Nebraska Methodist Hospital
🇺🇸Omaha, Nebraska, United States
Kidwai Institute of Oncology
🇮🇳Bangalore, India
Hollings Cancer Center
🇺🇸Charleston, South Carolina, United States
SEAROC Cancer Institute, S.K. Soni Hospital
🇮🇳Jaipur, India
Central India Cancer Research Institute
🇮🇳Nagpur, India
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Netaji Subhash Chandra Bose Cancer Hospital Research Institute
🇮🇳Kolkata, India
All India Institute of Medical Sciences
🇮🇳New Dehli, India
Vermont Cancer Center at Fletcher Allen Health Care
🇺🇸Burlington, Vermont, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Stanford Cancer Center
🇺🇸Stanford, California, United States
University of Colorado Cancer Center
🇺🇸Aurora, Colorado, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Peninsula Cancer Institute
🇺🇸Newport News, Virginia, United States
Gemeinschaftspraxis
🇩🇪Heidelberg, Germany
Johannes-Gutenberg Universitaet Mainz
🇩🇪Mainz, Germany
Universitaetsklinikum Tuebingen
🇩🇪Tuebingen, Germany
Klinikum der Ludwig-Maximilians-Universitaet Muenchen
🇩🇪Muenchen, Germany
Shatabdi Superspeciality Hospital
🇮🇳Nashik, India
Deenanath Mangeshkar Hospital & Research Center
🇮🇳Pune, India
UCLA
🇺🇸Los Angeles, California, United States
Yale University, School of Medicine
🇺🇸New Haven, Connecticut, United States
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
University of Alabama at Birmingham, Comprehensive Cancer Center
🇺🇸Birmingham, Alabama, United States
TGEN Clinical Research Service at Scottsdale Healthcare
🇺🇸Scottsdale, Arizona, United States
H. Lee Moffet Cancer Center and Research Institute
🇺🇸Tampa, Florida, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States
Capitol Comprehensive Cancer Care Clinic and Research Institute
🇺🇸Jefferson City, Missouri, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Multiple site locations
🇪🇸Barcelona, Spain
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
St. Luke's Hospital & Health Network
🇺🇸Bethlehem, Pennsylvania, United States
Cliniques Universitaires St. Luc
🇧🇪Brussels, Belgium
Universitaetsklinikum Leipzig
🇩🇪Leipzig, Germany
Klinik fuer Nuklearmedizin des Universitaetsklinikums Essen
🇩🇪Essen, Germany
Ludwig-Maximilians-Universitaet Muenchen
🇩🇪Muenchen, Germany
Universitaetsklinikum Wuerzburg
🇩🇪Wuerzburg, Germany
Indo-American Cancer Institute and Research Center
🇮🇳Hyderabad, India
Ruby Hall Clinic
🇮🇳Pune, India