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A Study of Two Different Doses of Cabozantinib (XL184) in Progressive, Metastatic Medullary Thyroid Cancer (EXAMINER)

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ClinicalTrials.gov Identifier: NCT01896479
Recruitment Status : Recruiting
First Posted : July 11, 2013
Last Update Posted : December 6, 2018
Sponsor:
Information provided by (Responsible Party):
Exelixis

Brief Summary:
The objective of this study is to evaluate the efficacy and safety of oral cabozantinib at a 60 mg dose compared with a 140 mg dose in subjects with progressive, metastatic MTC. It will test if the lower dose results in similar progression free survival (PFS) and overall response rate (ORR) with fewer adverse events compared to the PFS, ORR and adverse events found in previous clinical trials of 140 mg.

Condition or disease Intervention/treatment Phase
Medullary Thyroid Cancer Drug: Cabozantinib (XL184) 140 mg Drug: Cabozantinib (XL184) 60 mg Drug: Placebo tablet Drug: Placebo capsule Phase 4

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 188 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind Study To Evaluate the Efficacy and Safety of Cabozantinib (XL184) at 60 mg/Day Compared to a 140 mg/Day in Progressive, Metastatic Medullary Thyroid Cancer Patients
Study Start Date : December 2014
Estimated Primary Completion Date : May 2020
Estimated Study Completion Date : October 2020


Arm Intervention/treatment
Experimental: Cabozantinib (XL184) 140 mg
Cabozantinib (XL184) 140 mg as capsules and placebo tablets administered orally once a day.
Drug: Cabozantinib (XL184) 140 mg
Drug: Placebo tablet
Experimental: Cabozantinib (XL184) 60 mg
Cabozantinib (XL184) 60 mg as tablets and placebo capsules administered orally once a day.
Drug: Cabozantinib (XL184) 60 mg
Drug: Placebo capsule



Primary Outcome Measures :
  1. Progression Free Survival [ Time Frame: Up to 31 months ]
    PFS is measured from randomization until the date of first documented disease progression or date of death from any cause, whichever comes first. Assessed for up to 31 months.


Secondary Outcome Measures :
  1. Objective Response Rate [ Time Frame: Up to 31 months ]
    ORR is the proportion of subjects with measurable disease at baseline and who experience a best overall response of complete response (CR) or partial response (PR) which is confirmed ≥ 28 days later. Assessed for up to 31 months.


Other Outcome Measures:
  1. Safety and tolerability of cabozantinib as assessed by adverse events. [ Time Frame: Up to 31 months ]
    Adverse events are measured from informed consent and at least through 30 days after the date of a decision to discontinue study treatment. Assessed for up to 31 months.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. The subject has a histologically confirmed diagnosis of MTC.
  2. All subjects will need to be tested for RET mutational status. If subjects do not have documentation confirming they have a RET mutation, a sample of their tumor (taken either during screening or from a procedure within 6 months prior to randomization) will need to be tested.
  3. The subject has measurable disease per RECIST 1.1 that is metastatic as determined by the investigator based upon computerized tomography (CT), magnetic resonance imaging (MRI), PET scan, bone scan, or X-ray taken within 28 days before randomization.
  4. The subject has documented worsening of disease (progressive disease) at screening as compared with a previous CT, PETor MRI scan, bone scan, or X-ray as determined by the investigator per RECIST 1.1 on qualifying screening images taken within 28 days prior to randomization as compared to previous images taken within 14 months before the qualifying screening images.
  5. The subject has recovered to baseline or CTCAE v4.0 (Common Terminology Criteria for Adverse Events, version 4.0) ≤ Grade 1 from toxicities related to any prior treatments, unless AE(s) are clinically non-significant and/or stable on supportive therapy.
  6. The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 at screening.
  7. The subject has adequate organ and marrow function
  8. The subject is capable of understanding and complying with the protocol requirements and has signed the informed consent document.
  9. Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (eg, barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 4 months after the last dose of study treatment.

Exclusion Criteria:

  1. The subject has previously received cabozantinib.
  2. Receipt of any type of small molecule kinase inhibitor or hormonal therapy within 28 days or 5 half-lives of the compound or active metabolites, whichever is shorter, before randomization.
  3. Receipt of any systemic anti-tumor therapy within 28 days of randomization (42 days for nitrosoureas or/ mitomycin C).
  4. Receipt of any other type of investigational agent within 28 days of randomization.
  5. Receipt of radiation therapy within 28 days (14 days for radiation for bone metastases) of randomization or radionuclide treatment within 42 days of randomization. Subject is ineligible if there are any clinically relevant ongoing complications from prior radiation therapy.
  6. The subject has untreated and/or active (progressing or requiring anticonvulsants or corticosteroids for symptomatic control) central nervous system (CNS) metastasis. Must have completed radiation therapy ≥ 28 days prior to randomization and be stable without corticosteroids or anti-convulsant treatment for ≥ 10 days.
  7. Treatment at therapeutic doses with oral anticoagulants or platelet inhibitors (examples are warfarin and clopidogrel).
  8. The subject has uncontrolled, significant intercurrent illness including, but not limited to, cardiovascular disorders, gastrointestinal disorders, active infections, non-healing wounds, recent surgery.
  9. Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms within 28 days before randomization.
  10. The subject is unable to swallow multiple tablets or capsules.
  11. The subject has a previously identified allergy or hypersensitivity to components of the study treatment formulation.
  12. The subject is pregnant or breastfeeding.
  13. The subject has had a diagnosis of another malignancy within 2 years before randomization, except for superficial skin cancers, or localized, low-grade tumors deemed cured and not treated with systemic therapy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01896479


Contacts
Contact: Exelixis Clinical Trials 1-888-EXELIXIS (888-393-5494)
Contact: Backup or International 650-837-7400

  Show 52 Study Locations
Sponsors and Collaborators
Exelixis

Responsible Party: Exelixis
ClinicalTrials.gov Identifier: NCT01896479     History of Changes
Other Study ID Numbers: XL184-401
First Posted: July 11, 2013    Key Record Dates
Last Update Posted: December 6, 2018
Last Verified: December 2018

Keywords provided by Exelixis:
thyroid cancer
medullary thyroid cancer

Additional relevant MeSH terms:
Thyroid Diseases
Thyroid Neoplasms
Carcinoma, Neuroendocrine
Endocrine System Diseases
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue