Overview

This trial is active, not recruiting.

Condition thyroid cancer
Treatments xl184, placebo
Phase phase 3
Targets c-MET, AXL, FLT-3, KIT, RET, TIE2, TRKB, VEGF
Sponsor Exelixis
Start date June 2008
End date October 2011
Trial size 330 participants
Trial identifier NCT00704730, XL184-301

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
xl184
Gelatin capsules supplied in 25-mg and 100-mg strengths administered orally daily
(Placebo Comparator)
placebo
Gelatin capsules color and size-matched to XL184 capsules administered orally daily

Primary Outcomes

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.

Secondary Outcomes

Measure
Overall Survival (OS) With XL184 Compared With Placebo
time frame: 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)
time frame: 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
time frame: 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) %
time frame: 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) %
time frame: 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.

Eligibility Criteria

Male or female participants at least 18 years old.

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.

Additional Information

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
Trial information was received from ClinicalTrials.gov and was last updated in August 2015.
Information provided to ClinicalTrials.gov by Exelixis.