Efficacy of XL184 (Cabozantinib) in Advanced Medullary Thyroid Cancer

NCT00704730 | Completed Phase 3 Results DMC

• 1 other identifier: XL184-301
• Study Type: interventional
• Target: 330
• Locations: 24 countries
• Sites: 113

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.

Conditions

Thyroid Cancer

Keywords

Medullary Thyroid Cancer; MTC

Outcome Measures

Primary Outcomes (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.

  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)

• 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.

• 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.

• 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.

• 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.

• 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.

Study Arms (2)

1

EXPERIMENTAL

Drug: XL184

2

PLACEBO COMPARATOR

Drug: Placebo

Interventions

XL184 DRUG

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

1

Placebo DRUG

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

2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Exelixis: lead

Study Sites (113)

University of Alabama at Birmingham, Comprehensive Cancer Center

Birmingham, Alabama, 35294, United States

Location

TGEN Clinical Research Service at Scottsdale Healthcare

Scottsdale, Arizona, 85258, United States

Location

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Unknown Facility

Burbank, California, 91505, United States

Location

UCLA

Los Angeles, California, 90095, United States

Location

Stanford Cancer Center

Stanford, California, 94305, United States

Location

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

Yale University, School of Medicine

New Haven, Connecticut, 06520, United States

Location

Washington Cancer Institute

Washington D.C., District of Columbia, 20010, United States

Location

H. Lee Moffet Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Kansas University Medical Center

Kansas City, Kansas, 66160, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Capitol Comprehensive Cancer Care Clinic and Research Institute

Jefferson City, Missouri, 65109, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Nebraska Methodist Hospital

Omaha, Nebraska, 68114, United States

Location

Ohio State University, James Cancer Hospital

Columbus, Ohio, 43210, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

St. Luke's Hospital & Health Network

Bethlehem, Pennsylvania, 18015, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Hollings Cancer Center

Charleston, South Carolina, 29425, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Vermont Cancer Center at Fletcher Allen Health Care

Burlington, Vermont, 05401, United States

Location

Peninsula Cancer Institute

Newport News, Virginia, 23601, United States

Location

Unknown Facility

Klagenfurt, Austria

Location

Multiple site locations

Vienna, Austria

Location

Cliniques Universitaires St. Luc

Brussels, Belgium

Location

Universitair Ziekenhuis

Leuven, Belgium

Location

Unknown Facility

Brasília, Brazil

Location

Unknown Facility

Lajeado, Brazil

Location

Unknown Facility

Porto Alegre, Brazil

Location

Multiple site locations

São Paulo, Brazil

Location

Unknown Facility

Calgary, Alberta, Canada

Location

Unknown Facility

Toronto, Ontario, Canada

Location

CHUM - Hopital Saint-Luc

Montreal, Quebec, Canada

Location

Unknown Facility

Sherbrooke, Quebec, Canada

Location

Unknown Facility

Santiago, Chile

Location

Unknown Facility

Odense, Denmark

Location

Unknown Facility

Angers, France

Location

Unknown Facility

Bordeaux, France

Location

Unknown Facility

Lyon, France

Location

Unknown Facility

Marseille, France

Location

Unknown Facility

Reims, France

Location

Unknown Facility

Villejuif, France

Location

Klinik fuer Nuklearmedizin des Universitaetsklinikums Essen

Essen, Germany

Location

Gemeinschaftspraxis

Heidelberg, Germany

Location

Universitaetsklinikum Leipzig

Leipzig, Germany

Location

Johannes-Gutenberg Universitaet Mainz

Mainz, Germany

Location

Klinikum der Ludwig-Maximilians-Universitaet Muenchen

München, Germany

Location

Ludwig-Maximilians-Universitaet Muenchen

München, Germany

Location

Universitaetsklinikum Tuebingen

Tübingen, Germany

Location

Universitaetsklinikum Wuerzburg

Würzburg, Germany

Location

Unknown Facility

Athens, Greece

Location

Kidwai Institute of Oncology

Bangalore, India

Location

Indo-American Cancer Institute and Research Center

Hyderabad, India

Location

SEAROC Cancer Institute, S.K. Soni Hospital

Jaipur, India

Location

Netaji Subhash Chandra Bose Cancer Hospital Research Institute

Kolkata, India

Location

Central India Cancer Research Institute

Nagpur, India

Location

Shatabdi Superspeciality Hospital

Nashik, India

Location

All India Institute of Medical Sciences

New Dehli, India

Location

Deenanath Mangeshkar Hospital & Research Center

Pune, India

Location

Ruby Hall Clinic

Pune, India

Location

Unknown Facility

Haifa, Israel

Location

Unknown Facility

Jerusalem, Israel

Location

Unknown Facility

Petah Tikva, Israel

Location

Unknown Facility

Tel Aviv, Israel

Location

Unknown Facility

Florence, Italy

Location

Unknown Facility

Milan, Italy

Location

Unknown Facility

Naples, Italy

Location

Unknown Facility

Pisa, Italy

Location

Unknown Facility

Rome, Italy

Location

Unknown Facility

Siena, Italy

Location

Unknown Facility

Turin, Italy

Location

Unknown Facility

Amsterdam, Netherlands

Location

Unknown Facility

Groningen, Netherlands

Location

Unknown Facility

Leiden, Netherlands

Location

Multiple site locations

Lima, Peru

Location

Unknown Facility

Bydgoszcz, Poland

Location

Unknown Facility

Gliwice, Poland

Location

Unknown Facility

Pozan, Poland

Location

Unknown Facility

Szczecin, Poland

Location

Unknown Facility

Warsaw, Poland

Location

Unknown Facility

Coimbra, Portugal

Location

Unknown Facility

Porto, Portugal

Location

Unknown Facility

Obninsk, Russia

Location

Unknown Facility

Ufa, Russia

Location

Unknown Facility

Voronezh, Russia

Location

Unknown Facility

Yaroslavl, Russia

Location

Unknown Facility

Riyadh, Saudi Arabia

Location

Multiple site locations

Seoul, South Korea

Location

Multiple site locations

Barcelona, Spain

Location

Unknown Facility

Madrid, Spain

Location

Unknown Facility

Murcia, Spain

Location

Unknown Facility

Santiago de Compostela, Spain

Location

Unknown Facility

Seville, Spain

Location

Unknown Facility

Valencia, Spain

Location

Unknown Facility

Gothenburg, Sweden

Location

Unknown Facility

Lund, Sweden

Location

Unknown Facility

Uppsala, Sweden

Location

Unknown Facility

Bern, Switzerland

Location

Unknown Facility

Geneva, Switzerland

Location

Unknown Facility

Cardiff, United Kingdom

Location

Unknown Facility

Glasgow, United Kingdom

Location

Unknown Facility

London, United Kingdom

Location

Unknown Facility

Manchester, United Kingdom

Location

Unknown Facility

Newcastle upon Tyne, United Kingdom

Location

Unknown Facility

Oxford, United Kingdom

Location

Unknown Facility

Sheffield, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 29045520 DERIVED

• 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.

  PMID: 24002501 DERIVED

MeSH Terms

Conditions

Thyroid Neoplasms; Carcinoma, Medullary

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Ductal, Lobular, and Medullary; Neoplasms, Nerve Tissue

Results Point of Contact

• Title: Exelixis Medical Information
• Organization: Exelixis, Inc

druginfo@exelixis.com

855-292-3935

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2008
• First Posted: June 25, 2008
• Study Start: June 1, 2008
• Primary Completion: October 1, 2011
• Study Completion: September 1, 2020
• Last Updated: April 20, 2021
• Results First Posted: September 9, 2014

Record last verified: 2021-03

Locations

SA (1); RU (4); BR (4); DE (8); NL (3); FR (6); PL (5); AU (2); CL (1); IN (9); US (29); IT (7); PT (2); SE (3); CH (2); BE (2); ES (6); GR (1); IL (4); PE (1); KR (1); GB (7); DK (1); CA (4)