Efficacy of XL184 (Cabozantinib) in Advanced Medullary Thyroid Cancer (EXAM)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Exelixis
ClinicalTrials.gov Identifier:
NCT00704730
First received: June 23, 2008
Last updated: August 29, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Thyroid Cancer
Drug: XL184
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: An International, Randomized, Double-Blinded, Phase 3 Efficacy Study of XL184 Versus Placebo in Subjects With Unresectable, Locally Advanced, or Metastatic Medullary Thyroid Cancer

Resource links provided by NLM:


Further study details as provided by Exelixis:

Primary Outcome Measures:
  • Progression-Free Survival (PFS) [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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:
  • Overall Survival (OS) With XL184 Compared With Placebo [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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) [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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 [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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 Calcitonin (CTN) % [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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.

  • Biochemical Response Carcinoembryonic Antigen (CEA) % [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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.


Enrollment: 330
Study Start Date: June 2008
Estimated Study Completion Date: December 2014
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: XL184
Gelatin capsules supplied in 25-mg and 100-mg strengths administered orally daily
Placebo Comparator: 2 Drug: Placebo
Gelatin capsules color and size-matched to XL184 capsules administered orally daily

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00704730

  Hide Study Locations
Locations
United States, Alabama
University of Alabama at Birmingham, Comprehensive Cancer Center
Birmingham, Alabama, United States, 35294
United States, Arizona
TGEN Clinical Research Service at Scottsdale Healthcare
Scottsdale, Arizona, United States, 85258
United States, Arkansas
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
United States, California
Burbank, California, United States, 91505
UCLA
Los Angeles, California, United States, 90095
Stanford Cancer Center
Stanford, California, United States, 94305
United States, Colorado
University of Colorado Cancer Center
Aurora, Colorado, United States, 80045
United States, Connecticut
Yale University, School of Medicine
New Haven, Connecticut, United States, 06520
United States, District of Columbia
Washington Cancer Institute
Washington, District of Columbia, United States, 20010
United States, Florida
H. Lee Moffet Cancer Center and Research Institute
Tampa, Florida, United States, 33612
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
United States, Indiana
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202
United States, Iowa
University of Iowa
Iowa City, Iowa, United States, 52242
United States, Kansas
Kansas University Medical Center
Kansas City, Kansas, United States, 66160
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Michigan
Henry Ford Health System
Detroit, Michigan, United States, 48202
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Missouri
Capitol Comprehensive Cancer Care Clinic and Research Institute
Jefferson City, Missouri, United States, 65109
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, Nebraska
Nebraska Methodist Hospital
Omaha, Nebraska, United States, 68114
United States, Ohio
Ohio State University, James Cancer Hospital
Columbus, Ohio, United States, 43210
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
St. Luke's Hospital & Health Network
Bethlehem, Pennsylvania, United States, 18015
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, South Carolina
Hollings Cancer Center
Charleston, South Carolina, United States, 29425
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
United States, Vermont
Vermont Cancer Center at Fletcher Allen Health Care
Burlington, Vermont, United States, 05401
United States, Virginia
Peninsula Cancer Institute
Newport News, Virginia, United States, 23601
Austria
Klagenfurt, Austria
Multiple site locations
Wien, Austria
Belgium
Cliniques Universitaires St. Luc
Brussels, Belgium
Universitair Ziekenhuis
Leuven, Belgium
Brazil
Brasilia, Brazil
Lajeado, Brazil
Porto Alegre, Brazil
Multiple site locations
Sao Paulo, Brazil
Canada, Alberta
Calgary, Alberta, Canada
Canada, Ontario
Toronto, Ontario, Canada
Canada, Quebec
CHUM - Hopital Saint-Luc
Montreal, Quebec, Canada
Sherbrooke, Quebec, Canada
Chile
Santiago, Chile
Denmark
Odense, Denmark
France
Angers, France
Bordeaux, France
Lyon, France
Marseille, France
Reims, France
Villejuif, France
Germany
Klinik fuer Nuklearmedizin des Universitaetsklinikums Essen
Essen, Germany
Gemeinschaftspraxis
Heidelberg, Germany
Universitaetsklinikum Leipzig
Leipzig, Germany
Johannes-Gutenberg Universitaet Mainz
Mainz, Germany
Klinikum der Ludwig-Maximilians-Universitaet Muenchen
Muenchen, Germany
Ludwig-Maximilians-Universitaet Muenchen
Muenchen, Germany
Universitaetsklinikum Tuebingen
Tuebingen, Germany
Universitaetsklinikum Wuerzburg
Wuerzburg, Germany
Greece
Athens, Greece
India
Kidwai Institute of Oncology
Bangalore, India
Indo-American Cancer Institute and Research Center
Hyderabad, India
SEAROC Cancer Institute, S.K. Soni Hospital
Jaipur, India
Netaji Subhash Chandra Bose Cancer Hospital Research Institute
Kolkata, India
Central India Cancer Research Institute
Nagpur, India
Shatabdi Superspeciality Hospital
Nashik, India
All India Institute of Medical Sciences
New Dehli, India
Deenanath Mangeshkar Hospital & Research Center
Pune, India
Ruby Hall Clinic
Pune, India
Israel
Haifa, Israel
Jerusalem, Israel
Petach Tikva, Israel
Tel Aviv, Israel
Italy
Florence, Italy
Milan, Italy
Naples, Italy
Pisa, Italy
Rome, Italy
Siena, Italy
Turin, Italy
Korea, Republic of
Multiple site locations
Seoul, Korea, Republic of
Netherlands
Amsterdam, Netherlands
Groningen, Netherlands
Leiden, Netherlands
Peru
Multiple site locations
Lima, Peru
Poland
Bydgoszcz, Poland
Gliwice, Poland
Pozan, Poland
Szczecin, Poland
Warszawa, Poland
Portugal
Coimbra, Portugal
Oporto, Portugal
Porto, Portugal
Russian Federation
Obninsk, Russian Federation
Ufa, Russian Federation
Voronezh, Russian Federation
Yaroslavl, Russian Federation
Saudi Arabia
Riyadh, Saudi Arabia
Spain
Multiple site locations
Barcelona, Spain
Madrid, Spain
Murcia, Spain
Santiago de Compostela, Spain
Sevilla, Spain
Valencia, Spain
Sweden
Gothenburg, Sweden
Lund, Sweden
Uppsala, Sweden
Switzerland
Berne, Switzerland
Geneve, Switzerland
United Kingdom
Cardiff, United Kingdom
Glasgow, United Kingdom
London, United Kingdom
Manchester, United Kingdom
Newcastle Upon Tyne, United Kingdom
Oxford, United Kingdom
Sheffield, United Kingdom
Sponsors and Collaborators
Exelixis
  More Information

No publications provided by Exelixis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Exelixis
ClinicalTrials.gov Identifier: NCT00704730     History of Changes
Other Study ID Numbers: XL184-301
Study First Received: June 23, 2008
Results First Received: April 8, 2014
Last Updated: August 29, 2014
Health Authority: United States: Food and Drug Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Belgium: Federal Agency for Medicinal Products and Health Products
Denmark: Danish Medicines Agency
Netherlands: Medicines Evaluation Board (MEB)
Sweden: Medical Products Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Spain: Spanish Agency of Medicines
Canada: Health Canada
Israel: Ministry of Health
Germany: Federal Institute for Drugs and Medical Devices
Poland: Ministry of Health
Austria: Agency for Health and Food Safety
Italy: The Italian Medicines Agency
Greece: National Organization of Medicines
India: Drugs Controller General of India
Portugal: National Pharmacy and Medicines Institute
South Korea: Korea Food and Drug Administration (KFDA)
Russia: Ministry of Health of the Russian Federation
Chile: Comisión Nacional de Investigación Científica y Tecnológica
Peru: General Directorate of Pharmaceuticals, Devices, and Drugs
Brazil: Ministry of Health
Switzerland: Swissmedic
Saudi Arabia: Ethics Committee

Keywords provided by Exelixis:
Medullary Thyroid Cancer
MTC

Additional relevant MeSH terms:
Thyroid Diseases
Thyroid Neoplasms
Endocrine System Diseases
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms

ClinicalTrials.gov processed this record on September 18, 2014