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Thyroid CancerPhase 3EXAMNCT00704730

Efficacy of XL184 (Cabozantinib) in Advanced Medullary Thyroid Cancer

A Phase 3 study testing XL184 in people with Thyroid Cancer, run by Exelixis at 113 sites in 24 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Thyroid Cancer
What is being tested?
XL184
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
330 participants
Where
113 sitesin 24 countries
Study dates
Jun 2008to Sep 2020
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
Show all 10Show fewer
  • 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.

Trial locations and contacts

113 sites in 24 countries.

113 sites in 24 countries

United States29 sites

  • University of Colorado Cancer Center

    Aurora, Colorado, 80045

  • Johns Hopkins University

    Baltimore, Maryland, 21287

  • St. Luke's Hospital & Health Network

    Bethlehem, Pennsylvania, 18015

  • University of Alabama at Birmingham, Comprehensive Cancer Center

    Birmingham, Alabama, 35294

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Study site

    Burbank, California, 91505

  • Vermont Cancer Center at Fletcher Allen Health Care

    Burlington, Vermont, 05401

  • Hollings Cancer Center

    Charleston, South Carolina, 29425

  • University of Chicago

    Chicago, Illinois, 60637

  • Ohio State University, James Cancer Hospital

    Columbus, Ohio, 43210

  • Henry Ford Health System

    Detroit, Michigan, 48202

  • Indiana University Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202

  • University of Iowa

    Iowa City, Iowa, 52242

  • Capitol Comprehensive Cancer Care Clinic and Research Institute

    Jefferson City, Missouri, 65109

  • Kansas University Medical Center

    Kansas City, Kansas, 66160

  • University of Arkansas for Medical Sciences

    Little Rock, Arkansas, 72205

  • UCLA

    Los Angeles, California, 90095

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

  • Yale University, School of Medicine

    New Haven, Connecticut, 06520

  • Peninsula Cancer Institute

    Newport News, Virginia, 23601

  • Nebraska Methodist Hospital

    Omaha, Nebraska, 68114

  • Hospital of the University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Oregon Health & Science University

    Portland, Oregon, 97239

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • TGEN Clinical Research Service at Scottsdale Healthcare

    Scottsdale, Arizona, 85258

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Stanford Cancer Center

    Stanford, California, 94305

  • H. Lee Moffet Cancer Center and Research Institute

    Tampa, Florida, 33612

  • Washington Cancer Institute

    Washington D.C., District of Columbia, 20010

Other trials in United States

India9 sites

  • Kidwai Institute of Oncology

    Bangalore

  • Indo-American Cancer Institute and Research Center

    Hyderabad

  • SEAROC Cancer Institute, S.K. Soni Hospital

    Jaipur

  • Netaji Subhash Chandra Bose Cancer Hospital Research Institute

    Kolkata

  • Central India Cancer Research Institute

    Nagpur

  • Shatabdi Superspeciality Hospital

    Nashik

  • All India Institute of Medical Sciences

    New Dehli

  • Deenanath Mangeshkar Hospital & Research Center

    Pune

  • Ruby Hall Clinic

    Pune

Other trials in India

Germany8 sites

  • Klinik fuer Nuklearmedizin des Universitaetsklinikums Essen

    Essen

  • Gemeinschaftspraxis

    Heidelberg

  • Universitaetsklinikum Leipzig

    Leipzig

  • Johannes-Gutenberg Universitaet Mainz

    Mainz

  • Klinikum der Ludwig-Maximilians-Universitaet Muenchen

    München

  • Ludwig-Maximilians-Universitaet Muenchen

    München

  • Universitaetsklinikum Tuebingen

    Tübingen

  • Universitaetsklinikum Wuerzburg

    Würzburg

Other trials in Germany

Italy7 sites

  • Study site

    Florence

  • Study site

    Milan

  • Study site

    Naples

  • Study site

    Pisa

  • Study site

    Rome

  • Study site

    Siena

  • Study site

    Turin

Other trials in Italy

United Kingdom7 sites

  • Study site

    Cardiff

  • Study site

    Glasgow

  • Study site

    London

  • Study site

    Manchester

  • Study site

    Newcastle upon Tyne

  • Study site

    Oxford

  • Study site

    Sheffield

Other trials in United Kingdom

France6 sites

  • Study site

    Angers

  • Study site

    Bordeaux

  • Study site

    Lyon

  • Study site

    Marseille

  • Study site

    Reims

  • Study site

    Villejuif

Other trials in France

Spain6 sites

  • Multiple site locations

    Barcelona

  • Study site

    Madrid

  • Study site

    Murcia

  • Study site

    Santiago de Compostela

  • Study site

    Seville

  • Study site

    Valencia

Other trials in Spain

Poland5 sites

  • Study site

    Bydgoszcz

  • Study site

    Gliwice

  • Study site

    Pozan

  • Study site

    Szczecin

  • Study site

    Warsaw

Other trials in Poland

Brazil4 sites

  • Study site

    Brasília

  • Study site

    Lajeado

  • Study site

    Porto Alegre

  • Multiple site locations

    São Paulo

Other trials in Brazil

Canada4 sites

  • Study site

    Calgary, Alberta

  • CHUM - Hopital Saint-Luc

    Montreal, Quebec

  • Study site

    Sherbrooke, Quebec

  • Study site

    Toronto, Ontario

Other trials in Canada

Israel4 sites

  • Study site

    Haifa

  • Study site

    Jerusalem

  • Study site

    Petah Tikva

  • Study site

    Tel Aviv

Other trials in Israel

Russia4 sites

  • Study site

    Obninsk

  • Study site

    Ufa

  • Study site

    Voronezh

  • Study site

    Yaroslavl

Other trials in Russia

Netherlands3 sites

  • Study site

    Amsterdam

  • Study site

    Groningen

  • Study site

    Leiden

Other trials in Netherlands

Sweden3 sites

  • Study site

    Gothenburg

  • Study site

    Lund

  • Study site

    Uppsala

Other trials in Sweden

Austria2 sites

  • Study site

    Klagenfurt

  • Multiple site locations

    Vienna

Other trials in Austria

Belgium2 sites

  • Cliniques Universitaires St. Luc

    Brussels

  • Universitair Ziekenhuis

    Leuven

Other trials in Belgium

Portugal2 sites

  • Study site

    Coimbra

  • Study site

    Porto

Other trials in Portugal

Switzerland2 sites

  • Study site

    Bern

  • Study site

    Geneva

Other trials in Switzerland

Chile1 site

  • Study site

    Santiago

Other trials in Chile

Denmark1 site

  • Study site

    Odense

Other trials in Denmark

Greece1 site

  • Study site

    Athens

Other trials in Greece

Peru1 site

  • Multiple site locations

    Lima

Other trials in Peru

Saudi Arabia1 site

  • Study site

    Riyadh

Other trials in Saudi Arabia

South Korea1 site

  • Multiple site locations

    Seoul

Other trials in South Korea

About this study

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

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.

Conditions
Thyroid Cancer
Being tested
XL184, Placebo
Keywords
Medullary Thyroid Cancer, MTC
Medical subject headings
Thyroid Neoplasms, Carcinoma, Medullary

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • XL184Drug

    Gelatin capsules supplied in 25-mg and 100-mg strengths administered orally daily

  • PlaceboDrug

    Gelatin capsules color and size-matched to XL184 capsules administered orally daily

Study groups in NCT00704730
Study groupRoleWhat they receive
1ExperimentalNot described
Receives: Drug: XL184
2Placebo comparatorNot described
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-Free Survival (PFS)

    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.

    Measured: 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 (5)

  1. Overall Survival (OS) With XL184 Compared With Placebo

    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.

    Measured: 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.

  2. Objective Response Rate (ORR)

    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

    Measured: 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.

  3. Duration of Objective Response (OR): Independent Radiology Committee (IRC) Determined

    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.

    Measured: 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.

  4. Biochemical Response Calcitonin (CTN) %

    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.

    Measured: 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.

  5. Biochemical Response Carcinoembryonic Antigen (CEA) %

    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.

    Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jun 2008 (estimated)
  2. Study startJun 2008
  3. Primary completionOct 2011
  4. Study completionSep 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
330 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00704730
Sponsor's protocol ID
XL184-301
Acronym
EXAM
Status last verified
Mar 2021
First submitted
23 Jun 2008
Last updated
20 Apr 2021
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 29045520

  • 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.

    PubMed 24002501

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing XL184 in people with Thyroid Cancer, run by Exelixis at 113 sites in 24 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 113 sites in United States, India, Germany, Italy, United Kingdom and 19 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Sep 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00704730, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Apr 2021.

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