Clinical Trials /

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

NCT01896479

Description:

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.

Related Conditions:
  • Thyroid Gland Medullary Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 4

Trial Eligibility

Document

Title

  • Brief Title: A Study of Two Different Doses of Cabozantinib (XL184) in Progressive, Metastatic Medullary Thyroid Cancer
  • 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

Clinical Trial IDs

  • ORG STUDY ID: XL184-401
  • NCT ID: NCT01896479

Conditions

  • Medullary Thyroid Cancer

Interventions

DrugSynonymsArms
Cabozantinib (XL184) 140 mgCabozantinib (XL184) 140 mg
Cabozantinib (XL184) 60 mgCabozantinib (XL184) 60 mg
Placebo tabletCabozantinib (XL184) 140 mg
Placebo capsuleCabozantinib (XL184) 60 mg

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Cabozantinib (XL184) 140 mgExperimentalCabozantinib (XL184) 140 mg as capsules and placebo tablets administered orally once a day.
  • Cabozantinib (XL184) 140 mg
  • Placebo tablet
Cabozantinib (XL184) 60 mgExperimentalCabozantinib (XL184) 60 mg as tablets and placebo capsules administered orally once a day.
  • Cabozantinib (XL184) 60 mg
  • Placebo capsule

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival
Time Frame:Up to 31 months
Safety Issue:
Description: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

Measure:Objective Response Rate
Time Frame:Up to 31 months
Safety Issue:
Description: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.

Details

Phase:Phase 4
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Exelixis

Trial Keywords

  • thyroid cancer
  • medullary thyroid cancer

Last Updated

December 4, 2018