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Evaluation of Efficacy, Safety of Vandetanib in Patients With Differentiated Thyroid Cancer (VERIFY)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01876784
Recruitment Status : Active, not recruiting
First Posted : June 13, 2013
Results First Posted : March 13, 2017
Last Update Posted : April 9, 2021
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )

Tracking Information
First Submitted Date  ICMJE June 11, 2013
First Posted Date  ICMJE June 13, 2013
Results First Submitted Date  ICMJE January 23, 2017
Results First Posted Date  ICMJE March 13, 2017
Last Update Posted Date April 9, 2021
Actual Study Start Date  ICMJE September 17, 2013
Actual Primary Completion Date August 30, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 23, 2017)
Progression-Free Survival (PFS) [ Time Frame: Randomization until disease progression or death, assessed every 12 weeks (up to 22 months) ]
The PFS was defined as the time (in months) from randomization until the date of first documented disease progression or death (from any cause), whichever came first. Disease progression as per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) was defined as: at least a 20% increase and absolute increase of 5 mm in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Analysis was performed by Kaplan-Meier method.
Original Primary Outcome Measures  ICMJE
 (submitted: June 11, 2013)
Determination of the efficacy (as assessed by progression-free survival) of vandetanib when compared to placebo in the patient population [ Time Frame: Estimated time frame up to 25.5 months (18 months recruitment period plus 7.5 months follow-up). ]
Once 155 progression events have occurred. RECIST measurements taken every 12 weeks from randomization. Time point(s) at which outcome measure is assessed.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 23, 2017)
  • Determination of the Efficacy of Vandetanib When Compared to Placebo in the Patient Population as Assessed by Efficacy Variables Including Duration of Response. [ Time Frame: Estimated time frame up to 25.5 months (18 months recruitment period plus 7.5 months follow up). RECIST measurements taken every 12 weeks from randomization ]
    Once 155 progression events have occurred.
  • Demonstration of an Improvement in Time to Worsening of Pain in Patients Treated With Vandetanib When Compared to Placebo in the Patient Population. [ Time Frame: Patient assessments at baseline, week 4, 8, 12 and then every 12 weeks thereafter, assess up to 25.5 months ]
    Once 155 progression events have occurred.
  • Evaluation of the Safety and Tolerability of Vandetanib Treatment in the Patient Population by Assessment of Adverse Events, Vital Signs, Laboratory Parameters and Electrocardiography. [ Time Frame: Safety assessments at baseline, Weeks 1, 2, 4, 8, 12 and then every 12 weeks thereafter ]
    Once 155 progression events have occurred.
  • Determination of the Efficacy of Vandetanib When Compared to Placebo in the Patient Population as Assessed by Efficacy Variables Including Objective Response Rate. [ Time Frame: Estimated time frame up to 25.5 months (18 months recruitment period plus 7.5 months follow up). RECIST measurements taken every 12 weeks from randomization ]
    Once 155 progression events have occurred.
  • Determination of the Efficacy of Vandetanib When Compared to Placebo in the Patient Population as Assessed by Efficacy Variables Including Change in Tumour Size [ Time Frame: Assessed tumour size at screening, Weeks 7, 8 and then every 12 weeks thereafter and at Discontinuation visit, estimated time frame at 25.5 months. ]
    Once 155 progression events have occurred.
  • Determination of the Efficacy of Vandetanib When Compared to Placebo in the Patient Population as Assessed by Efficacy Variables Including Overall Survival [ Time Frame: Estimated time frame at 20 months after initial 25.5 months. ]
    Once 155 progression events have occurred when 25% of randomized patients have died due to any cause.
  • Evaluation of the Pharmacokinetics of Vandetanib in the Patient Population by Assessment of V/F. [ Time Frame: Blood sampling at 4-6 hours post-dose at Weeks 1, 2, 4, 8, 12 and then every 12 weeks thereafter until discontinuation. ]
    Estimated time frame up to 155 progression events have occurred or up to individual progression of patient.
  • Evaluation of the Pharmacokinetics of Vandetanib in the Patient Population by Assessment of Cmax [ Time Frame: Blood sampling at 4-6 hours post-dose at Weeks 1, 2, 4, 8, 12 and then every 12 weeks thereafter until discontinuation. ]
    Estimated time frame up to 155 progression events have occurred or up to individual progression of patient.
  • Evaluation of the Pharmacokinetics of Vandetanib in the Patient Population by Assessment of AUCss [ Time Frame: Blood sampling at 4-6 hours post-dose at Weeks 1, 2, 4, 8, 12 and then every 12 weeks thereafter until discontinuation. ]
    Estimated time frame up to 155 progression events have occurred or up to individual progression of patient.
  • Evaluation of the Pharmacokinetics of Vandetanib in the Patient Population by Assessment of CL/F [ Time Frame: Blood sampling at 4-6 hours post-dose at Weeks 1, 2, 4, 8, 12 and then every 12 weeks thereafter until discontinuation. ]
    Estimated time frame up to 155 progression events have occurred or up to individual progression of patient.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 11, 2013)
  • Determination of the Efficacy of Vandetanib When Compared to Placebo in the Patient Population as Assessed by Efficacy Variables Including Duration of Response. [ Time Frame: Estimated time frame at 20 months after initial 25.5 months. ]
    Once 155 progression events have occurred. Analysis of overall survival to be repeated when 50% of randomised patients have died due to any cause.
  • Demonstration of an Improvement in Time to Worsening of Pain in Patients Treated With Vandetanib When Compared to Placebo in the Patient Population. [ Time Frame: Patient assessments at baseline, week 4, 8, 12 and then 12 weekly thereafter, assess up to 25.5 months ]
    Estimated time frame up to 155 progression events have occured.
  • Evaluation of the Safety and Tolerability of Vandetanib Treatment in the Patient Population by Assessment of Adverse Events, Vital Signs, Laboratory Parameters and Electrocardiography. [ Time Frame: Safety assessments at baseline, Weeks 1, 2, 4, 8, 12 and then 12 weekly thereafter, assess up to 25.5 months ]
    Once 155 progression events have occurred.
  • Determination of the Efficacy of Vandetanib When Compared to Placebo in the Patient Population as Assessed by Efficacy Variables Including Objective Response Rate. [ Time Frame: Estimated time frame at 20 months after initial 25.5 months. ]
    Once 155 progression events have occurred. Analysis of overall survival to be repeated when 50% of randomised patients have died due to any cause.
  • Determination of the Efficacy of Vandetanib When Compared to Placebo in the Patient Population as Assessed by Efficacy Variables Including Change in Tumour Size [ Time Frame: Assessed tumour size at screening, Weeks 7, 8 and then 12 weekly thereafter and at Discontinuation visit, estimated time frame at 25.5 months. ]
    Once 155 progression events have occurred. Analysis of overall survival to be repeated when 50% of randomised patients have died due to any cause.
  • Determination of the Efficacy of Vandetanib When Compared to Placebo in the Patient Population as Assessed by Efficacy Variables Including Overall Survival [ Time Frame: Estimated time frame at 20 months after initial 25.5 months. ]
    Once 155 progression events have occurred. Analysis of overall survival to be repeated when 50% of randomised patients have died due to any cause.
  • Evaluation of the Pharmacokinetics of Vandetanib in the Patient Population by Assessment of V/F. [ Time Frame: Blood sampling at 4-6 hours post-dose at Weeks 1, 2, 4, 8, 12 and then 12 weekly thereafter until discontinuation. ]
    Estimated time frame up to 155 progression events have occured or up to individual progression of patient.
  • Evaluation of the Pharmacokinetics of Vandetanib in the Patient Population by Assessment of Cmax [ Time Frame: Blood sampling at 4-6 hours post-dose at Weeks 1, 2, 4, 8, 12 and then 12 weekly thereafter until discontinuation. ]
    Estimated time frame up to 155 progression events have occured or up to individual progression of patient.
  • Evaluation of the Pharmacokinetics of Vandetanib in the Patient Population by Assessment of AUCss [ Time Frame: Blood sampling at 4-6 hours post-dose at Weeks 1, 2, 4, 8, 12 and then 12 weekly thereafter until discontinuation. ]
    Estimated time frame up to 155 progression events have occured or up to individual progression of patient.
  • Evaluation of the Pharmacokinetics of Vandetanib in the Patient Population by Assessment of CL/F [ Time Frame: Blood sampling at 4-6 hours post-dose at Weeks 1, 2, 4, 8, 12 and then 12 weekly thereafter until discontinuation. ]
    Estimated time frame up to 155 progression events have occured or up to individual progression of patient.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation of Efficacy, Safety of Vandetanib in Patients With Differentiated Thyroid Cancer
Official Title  ICMJE A Randomized, Double-Blind, Placebo-Controlled, Multi-Centre Phase III Study to Assess the Efficacy and Safety of Vandetanib (CAPRELSA™; SAR390530 (Formerly AstraZeneca ZD6474)) 300 mg in Patients With Differentiated Thyroid Cancer That Is Either Locally Advanced or Metastatic Who Are Refractory or Unsuitable for Radioiodine (RAI) Therapy.
Brief Summary

Primary Objective:

To determine the efficacy (as assessed by progression-free survival [PFS]) of vandetanib when compared to placebo in participants with differentiated thyroid cancer that is either locally advanced or metastatic who are refractory or unsuitable for radioiodine therapy.

Secondary Objectives:

  • To determine the efficacy of vandetanib when compared to placebo in this participant population as assessed by efficacy variables including duration of response (DOR), objective response rate (ORR), change in tumour size (TS) and overall survival (OS).
  • To evaluate the pharmacokinetics (PK) of vandetanib in this participant population and potentially investigate any influence of participant demography and pathophysiology on vandetanib PK.
  • To demonstrate an improvement in time to worsening of pain (TWP) in participants treated with vandetanib when compared to placebo in this participant population.
  • To evaluate the safety and tolerability of vandetanib treatment in this participant population.
Detailed Description Participants who were receiving vandetanib as randomized treatment will be allowed, upon re-consent, to continue on open-label vandetanib if in the opinion of the Investigator the participant is still receiving benefit. Placebo participants who experience disease progression within 60 days of unblinding may be offered the option of treatment with open-label vandetanib if, in the Investigator's opinion, such treatment may be of clinical benefit to the participant. Approximately 2 years; duration will vary depending on individual participant response.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Differentiated Thyroid Cancer
Intervention  ICMJE
  • Drug: Vandetanib (SAR390530)

    Pharmaceutical form: tablet

    Route of administration: oral

    Other Name: CAPRELSA
  • Drug: Placebo

    Pharmaceutical form: tablet

    Route of administration: oral

Study Arms  ICMJE
  • Experimental: Vandetanib
    Vandetanib 300 mg tablet, orally once daily until disease progression or death.
    Intervention: Drug: Vandetanib (SAR390530)
  • Placebo Comparator: Placebo
    Placebo matched to vandetanib tablet, orally once daily until disease progression or death.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: August 7, 2017)
243
Original Estimated Enrollment  ICMJE
 (submitted: June 11, 2013)
227
Estimated Study Completion Date  ICMJE December 31, 2021
Actual Primary Completion Date August 30, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Provision of informed consent to participate in the study as well as provision of informed consent to provide a sample of a previously obtained archival tumour biopsy.
  • Female or male aged 18 years and older with previously confirmed histological diagnosis of locally advanced or metastatic differentiated (excluding minimally invasive follicular) thyroid cancer not amenable to surgical resection, external beam radiotherapy or local therapy.
  • Measurable disease defined as at least one lesion, not irradiated within 12 weeks of the date of randomisation, that can be accurately measured at baseline.
  • Participants must have experienced progression within 14 months and be RAI-refractory/resistant or unsuitable for RAI.
  • Thyroid-stimulating hormone (TSH) suppression below 0.5 mU/L is required.
  • World Health Organisation (WHO) or Eastern Cooperative Oncology Group (ECOG) Performance status 0-2.
  • Negative pregnancy test (urine or serum) for female participants of childbearing potential.

Exclusion Criteria:

  • Inadequate organ function as defined by: (1) Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase (ALP) greater than 2.5 x upper limit of normal (ULN), or greater than 5.0 x ULN if judged by the Investigator to be related to liver metastases. (2) Serum bilirubin greater than 1.5 x ULN. This criterion does not apply to participants with known Gilbert's Disease. (3) Creatinine clearance <50 mL/min (calculated by Cockcroft-Gault formula).
  • Risk of prolonged interval between Q and T (QT) on an electrocardiogram (ECG) corrected for heart rate (QTc) as defined by: (1) Current therapy with any medication known to be associated with Torsades de pointes or potent inducers of cytochrome CYP3A4. (2) History of QT prolongation. (3) Congenital long QT syndrome. (4) QT interval corrected for heart rate by the Bazett's method (QTcB) correction unmeasurable or greater than 480 ms on screening ECG.
  • Previous therapy with approved or investigational tyrosine kinase or anti- vascular endothelial growth factor (VEGF) receptor inhibitors or targeted therapies (e.g. multi-targeted kinase inhibitors such as sorafenib, AMG-706, sunitinib, pazopanib, lenvatinib).
  • RAI therapy within 12 weeks prior to first dose of study drug, and radiation therapy other than RAI, including external beam, if not completed prior to randomization.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Brazil,   China,   Czechia,   Denmark,   France,   Italy,   Japan,   Poland,   Russian Federation,   Spain,   Sweden,   United States
Removed Location Countries Belgium,   Czech Republic,   Germany,   Hungary,   Romania,   United Kingdom
 
Administrative Information
NCT Number  ICMJE NCT01876784
Other Study ID Numbers  ICMJE D4203C00011
2013-000422-58 ( EudraCT Number )
LPS14813 ( Other Identifier: Sanofi )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sanofi ( Genzyme, a Sanofi Company )
Study Sponsor  ICMJE Genzyme, a Sanofi Company
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Sciences & Operations Sanofi
PRS Account Sanofi
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP