Efficacy of XL184 (Cabozantinib) in Advanced Medullary Thyroid Cancer (EXAM)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Exelixis
ClinicalTrials.gov Identifier:
NCT00704730
First received: June 23, 2008
Last updated: August 29, 2014
Last verified: August 2014
  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 3

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:


Further study details as provided by Exelixis:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
    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.

  • 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. ] [ Designated as safety issue: No ]
    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

  • 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. ] [ Designated as safety issue: No ]
    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.

  • 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. ] [ Designated as safety issue: No ]
    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.

  • 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. ] [ Designated as safety issue: No ]
    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.


Enrollment: 330
Study Start Date: June 2008
Estimated Study Completion Date: December 2014
Primary Completion Date: October 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 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

  Show 114 Study Locations
Sponsors and Collaborators
Exelixis
  More Information

No publications provided by Exelixis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Exelixis
ClinicalTrials.gov Identifier: NCT00704730     History of Changes
Other Study ID Numbers: XL184-301
Study First Received: June 23, 2008
Results First Received: April 8, 2014
Last Updated: August 29, 2014
Health Authority: United States: Food and Drug Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
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 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 Diseases
Thyroid Neoplasms
Endocrine System Diseases
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms

ClinicalTrials.gov processed this record on September 16, 2014