Efficacy of XL184 (Cabozantinib) in Advanced Medullary Thyroid Cancer - Full Text View

Sponsor:	Exelixis
Information provided by:	Exelixis
ClinicalTrials.gov Identifier:	NCT00704730

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 III

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:

MedlinePlus related topics: Cancer Thyroid Cancer Thyroid Diseases

Drug Information available for: Thyroid

U.S. FDA Resources

Further study details as provided by Exelixis:

Primary Outcome Measures:

To evaluate progression-free survival (PFS) with XL184 as compared with placebo in subjects with unresectable, locally advanced, or metastatic medullary thyroid cancer (MTC) [ Time Frame: Assessed at periodic visits ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To evaluate overall survival (OS) with XL184 as compared with placebo [ Time Frame: Assessed as applicable ] [ Designated as safety issue: No ]
To evaluate the objective response rate (ORR) and duration of response in subjects with measurable disease with XL184 as compared with placebo [ Time Frame: Assessed at periodic visits ] [ Designated as safety issue: No ]
To evaluate the safety and tolerability of XL184 [ Time Frame: Assessed at periodic visits ] [ Designated as safety issue: Yes ]
To assess the pharmacokinetics and pharmacodynamic effects of XL184 [ Time Frame: Assessed at periodic visits ] [ Designated as safety issue: No ]

Estimated Enrollment:	315
Study Start Date:	June 2008
Estimated Study Completion Date:	March 2013
Estimated Primary Completion Date:	August 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 is 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

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

Show 114 Study Locations

Sponsors and Collaborators

Exelixis

More Information

No publications provided

Responsible Party:	Steve Sagar, MD/Senior Director, Clinical Research, Exelixis
ClinicalTrials.gov Identifier:	NCT00704730 History of Changes
Other Study ID Numbers:	XL184-301
Study First Received:	June 23, 2008
Last Updated:	June 2, 2011
Health Authority:	United States: Food and Drug Administration; France: Afssaps - French Health Products Safety Agency; 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 and Social Development 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 Neoplasms
Thyroid Diseases
Endocrine Gland Neoplasms
Neoplasms by Site

Neoplasms
Head and Neck Neoplasms
Endocrine System Diseases

ClinicalTrials.gov processed this record on February 09, 2012