Efficacy Study of XL184 in Adults With Medullary Thyroid Cancer


Tracking Information

Start Date  ICMJEJune 2008
Estimated Primary Completion DateJune 2010   (final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 3, 2008)
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 ]
Original Primary Outcome Measures ICMJE 
 (submitted: June 23, 2008)
To evaluate progression-free survival (PFS) with XL184 treatment 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 ]
Change HistoryComplete list of historical versions of study NCT00704730 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE 
 (submitted: September 3, 2008)
  • 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 ]
Original Secondary Outcome Measures ICMJE 
 (submitted: June 23, 2008)
  • To evaluate overall survival (OS) with XL184 treatment 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 treatment as compared with placebo [ Time Frame: Assessed at periodic visits ] [ Designated as safety issue: No ]
  • To evaluate the safety and tolerability of XL184 treatment [ Time Frame: Assessed at periodic visits ] [ Designated as safety issue: Yes ]
  • To assess the pharmacokinetics and pharmacodynamic effects of XL184 treatment [ Time Frame: Assessed at periodic visits ] [ Designated as safety issue: No ]

Descriptive Information

Brief Title  ICMJEEfficacy Study of XL184 in Adults With Medullary Thyroid Cancer
Official Title  ICMJEAn International, Randomized, Double-Blinded, Phase 3 Efficacy Study of XL184 Versus Placebo in Subjects With Unresectable, Locally Advanced, or Metastatic Medullary Thyroid Cancer
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.

Site/location information will be updated periodically.

Detailed Description 
Study PhasePhase III
Study Type  ICMJEInterventional
Study Design  ICMJETreatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study
Condition  ICMJEThyroid Cancer
Intervention  ICMJE
  • Drug: XL184
    Gelatin capsules supplied in 25-mg and 100-mg strengths administered orally daily
  • Drug: Placebo
    Gelatin capsules color and size-matched to XL184 capsules administered orally daily
Study Arms / Comparison Groups
  • 1: Experimental
    Intervention: Drug: XL184
  • 2: Placebo Comparator
    Intervention: Drug: Placebo

Recruitment Information

Estimated Enrollment  ICMJE315
Estimated Completion DateMarch 2013
Estimated Primary Completion DateJune 2010   (final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
GenderBoth
Ages18 Years and older
Accepts Healthy VolunteersNo
Contacts  ICMJE
Contact: Exelixis Contact Line1-866-939-4041
Location Countries  ICMJEUnited States,   Austria,   Belgium,   Canada,   Denmark,   France,   Germany,   Greece,   India,   Israel,   Italy,   Netherlands,   Poland,   Russian Federation,   Spain,   Sweden,   United Kingdom

Administrative Information

NCT ID  ICMJENCT00704730
Responsible PartyRon Weitzman, MD/Vice President, Clinical Research, Exelixis
Study ID Numbers  ICMJEXL184-301
Study Sponsor  ICMJEExelixis
Collaborators  ICMJE 
Investigators  ICMJE 
Information Provided ByExelixis