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NCT00704730 · CITED IN SOURCE DOCUMENTS

Efficacy of XL184 (Cabozantinib) in Advanced Medullary Thyroid Cancer

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE3
Status at capture
COMPLETED
Registry last update
2021-04-20

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Progression-Free Survival (PFS)

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outcome · POSTED

Overall Survival (OS) With XL184 Compared With Placebo

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outcome · POSTED

Objective Response Rate (ORR)

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outcome · POSTED

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

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outcome · POSTED

Biochemical Response Calcitonin (CTN) %

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outcome · POSTED

Biochemical Response Carcinoembryonic Antigen (CEA) %

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility Criteria
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.
healthy Volunteers
false
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. intervention Names
    1. Drug: XL184
    label
    1
    type
    EXPERIMENTAL
  2. intervention Names
    1. Drug: Placebo
    label
    2
    type
    PLACEBO_COMPARATOR
interventions
  1. arm Group Labels
    1. 1
    description
    Gelatin capsules supplied in 25-mg and 100-mg strengths administered orally daily
    name
    XL184
    type
    DRUG
  2. arm Group Labels
    1. 2
    description
    Gelatin capsules color and size-matched to XL184 capsules administered orally daily
    name
    Placebo
    type
    DRUG
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
QUADRUPLE
who Masked
  1. PARTICIPANT
  2. CARE_PROVIDER
  3. INVESTIGATOR
  4. OUTCOMES_ASSESSOR
primary Purpose
TREATMENT
Enrollment
count
330
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    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.
    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
  1. description
    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.
    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.
  2. description
    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
    measure
    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.
  3. description
    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.
    measure
    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.
  4. description
    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.
    measure
    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.
  5. description
    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.
    measure
    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.
Full study description
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.
Source references
references
  1. citation
    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
    type
    DERIVED
  2. citation
    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
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
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      occurrences
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        s="pdq-content-list"><ol id="_1100"><li>Cabozantinib was evaluated in a randomized, double-blind, placebo-controlled, phase III trial (<a href="/clinicaltrials/NCT00704730">EXAM</a> [NCT00704730]). The study included 330 patients with metastatic MTC and radiographic progression of disease. Patients were randomly assigned in a 2:
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      2. context exact
        id="_1100"><li>Cabozantinib was evaluated in a randomized, double-blind, placebo-controlled, phase III trial (<a href="/clinicaltrials/NCT00704730">EXAM</a> [NCT00704730]). The study included 330 patients with metastatic MTC and radiographic progression of disease. Patients were randomly assigned in a 2:1 ratio to receive caboz
        end
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      source retrieved at
      2026-09-09T23:22:23.753084+00:00
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      source string sha256
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      source title
      Thyroid Cancer Treatment (PDQ®)–Health Professional Version
      source update dates
      1. context
        Updated: May 9, 2025
        datetime
        2025-05-09T12:00:00Z
        display
        May 9, 2025

    Preserved source evidence · Not medical advice