Clinical trial NCT00704730: Efficacy of XL184 (Cabozantinib) in Advanced Medullary Thyroid Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Thyroid Cancer
Keywords: Medullary Thyroid Cancer
MTC
Lead sponsor: Exelixis
Sponsor class: INDUSTRY
First posted: 2008-06-25
Enrollment: 330
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: 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.
Secondary outcomes:
measure: Overall Survival (OS) With XL184 Compared With Placebo
timeFrame: 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.
measure: Objective Response Rate (ORR)
timeFrame: 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.
measure: Duration of Objective Response (OR): Independent Radiology Committee (IRC) Determined
timeFrame: 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.
measure: Biochemical Response Calcitonin (CTN) %
timeFrame: 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.
measure: Biochemical Response Carcinoembryonic Antigen (CEA) %
timeFrame: 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.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham, Comprehensive Cancer Center
state: Alabama
city: Scottsdale
country: United States
facility: TGEN Clinical Research Service at Scottsdale Healthcare
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Burbank
country: United States
state: California
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Stanford
country: United States
facility: Stanford Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: New Haven
country: United States
facility: Yale University, School of Medicine
state: Connecticut
city: Washington
country: United States
facility: Washington Cancer Institute
state: District of Columbia
city: Tampa
country: United States
facility: H. Lee Moffet Cancer Center and Research Institute
state: Florida
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bren Simon Cancer Center
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Kansas City
country: United States
facility: Kansas University Medical Center
state: Kansas
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Jefferson City
country: United States
facility: Capitol Comprehensive Cancer Care Clinic and Research Institute
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: Nebraska Methodist Hospital
state: Nebraska
city: Columbus
country: United States
facility: Ohio State University, James Cancer Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Bethlehem
country: United States
facility: St. Luke's Hospital & Health Network
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Charleston
country: United States
facility: Hollings Cancer Center
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Burlington
country: United States
facility: Vermont Cancer Center at Fletcher Allen Health Care
state: Vermont
city: Newport News
country: United States
facility: Peninsula Cancer Institute
state: Virginia
city: Klagenfurt
country: Austria
city: Wien
country: Austria
facility: Multiple site locations
city: Brussels
country: Belgium
facility: Cliniques Universitaires St. Luc
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis
city: Brasilia
country: Brazil
city: Lajeado
country: Brazil
city: Porto Alegre
country: Brazil
city: Sao Paulo
country: Brazil
facility: Multiple site locations
city: Calgary
country: Canada
state: Alberta
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
facility: CHUM - Hopital Saint-Luc
state: Quebec
city: Sherbrooke
country: Canada
state: Quebec
city: Santiago
country: Chile
city: Odense
country: Denmark
city: Angers
country: France
city: Bordeaux
country: France
city: Lyon
country: France
city: Marseille
country: France
city: Reims
country: France
city: Villejuif
country: France
city: Essen
country: Germany
facility: Klinik fuer Nuklearmedizin des Universitaetsklinikums Essen
city: Heidelberg
country: Germany
facility: Gemeinschaftspraxis
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig
city: Mainz
country: Germany
facility: Johannes-Gutenberg Universitaet Mainz
city: Muenchen
country: Germany
facility: Klinikum der Ludwig-Maximilians-Universitaet Muenchen
city: Muenchen
country: Germany
facility: Ludwig-Maximilians-Universitaet Muenchen
city: Tuebingen
country: Germany
facility: Universitaetsklinikum Tuebingen
city: Wuerzburg
country: Germany
facility: Universitaetsklinikum Wuerzburg
city: Athens
country: Greece
city: Bangalore
country: India
facility: Kidwai Institute of Oncology
city: Hyderabad
country: India
facility: Indo-American Cancer Institute and Research Center
city: Jaipur
country: India
facility: SEAROC Cancer Institute, S.K. Soni Hospital
city: Kolkata
country: India
facility: Netaji Subhash Chandra Bose Cancer Hospital Research Institute
city: Nagpur
country: India
facility: Central India Cancer Research Institute
city: Nashik
country: India
facility: Shatabdi Superspeciality Hospital
city: New Dehli
country: India
facility: All India Institute of Medical Sciences
city: Pune
country: India
facility: Deenanath Mangeshkar Hospital & Research Center
city: Pune
country: India
facility: Ruby Hall Clinic
city: Haifa
country: Israel
city: Jerusalem
country: Israel
city: Petach Tikva
country: Israel
city: Tel Aviv
country: Israel
city: Florence
country: Italy
city: Milan
country: Italy
city: Naples
country: Italy
city: Pisa
country: Italy
city: Rome
country: Italy
city: Siena
country: Italy
city: Turin
country: Italy
city: Seoul
country: Korea, Republic of
facility: Multiple site locations
city: Amsterdam
country: Netherlands
city: Groningen
country: Netherlands
city: Leiden
country: Netherlands
city: Lima
country: Peru
facility: Multiple site locations
city: Bydgoszcz
country: Poland
city: Gliwice
country: Poland
city: Pozan
country: Poland
city: Szczecin
country: Poland
city: Warszawa
country: Poland
city: Coimbra
country: Portugal
city: Oporto
country: Portugal
city: Porto
country: Portugal
city: Obninsk
country: Russian Federation
city: Ufa
country: Russian Federation
city: Voronezh
country: Russian Federation
city: Yaroslavl
country: Russian Federation
city: Riyadh
country: Saudi Arabia
city: Barcelona
country: Spain
facility: Multiple site locations
city: Madrid
country: Spain
city: Murcia
country: Spain
city: Santiago de Compostela
country: Spain
city: Sevilla
country: Spain
city: Valencia
country: Spain
city: Gothenburg
country: Sweden
city: Lund
country: Sweden
city: Uppsala
country: Sweden
city: Berne
country: Switzerland
city: Geneve
country: Switzerland
city: Cardiff
country: United Kingdom
city: Glasgow
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
city: Newcastle Upon Tyne
country: United Kingdom
city: Oxford
country: United Kingdom
city: Sheffield
country: United Kingdom
Study officials:
References:
citation: Schlumberger M, Elisei R, Muller S, Schoffski P, Brose M, Shah M, Licitra L, Krajewska J, Kreissl MC, Niederle B, Cohen EEW, Wirth L, Ali H, Clary DO, Yaron Y, Mangeshkar M, Ball D, Nelkin B, Sherman S. Overall survival analysis of EXAM, a phase III trial of cabozantinib in patients with radiographically progressive medullary thyroid carcinoma. Ann Oncol. 2017 Nov 1;28(11):2813-2819. doi: 10.1093/annonc/mdx479.
citation: Elisei R, Schlumberger MJ, Muller SP, Schoffski P, Brose MS, Shah MH, Licitra L, Jarzab B, Medvedev V, Kreissl MC, Niederle B, Cohen EE, Wirth LJ, Ali H, Hessel C, Yaron Y, Ball D, Nelkin B, Sherman SI. Cabozantinib in progressive medullary thyroid cancer. J Clin Oncol. 2013 Oct 10;31(29):3639-46. doi: 10.1200/JCO.2012.48.4659. Epub 2013 Sep 3.