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

Primary Purpose

Differentiated Thyroid Cancer

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Vandetanib (SAR390530)
Placebo
Sponsored by
Genzyme, a Sanofi Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Differentiated Thyroid Cancer focused on measuring vandetanib, AZD 6474, Differentiated Thyroid Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

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  • Washington University
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Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Vandetanib

Placebo

Arm Description

Vandetanib 300 mg tablet, orally once daily until disease progression or death.

Placebo matched to vandetanib tablet, orally once daily until disease progression or death.

Outcomes

Primary Outcome Measures

Progression-Free Survival (PFS)
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.

Secondary Outcome Measures

Determination of the Efficacy of Vandetanib When Compared to Placebo in the Patient Population as Assessed by Efficacy Variables Including Duration of Response.
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.
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.
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.
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
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
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.
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
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
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
Estimated time frame up to 155 progression events have occurred or up to individual progression of patient.

Full Information

First Posted
June 11, 2013
Last Updated
January 6, 2023
Sponsor
Genzyme, a Sanofi Company
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1. Study Identification

Unique Protocol Identification Number
NCT01876784
Brief Title
Evaluation of Efficacy, Safety of Vandetanib in Patients With Differentiated Thyroid Cancer
Acronym
VERIFY
Official Title
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.
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Completed
Study Start Date
September 17, 2013 (Actual)
Primary Completion Date
August 30, 2015 (Actual)
Study Completion Date
January 22, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genzyme, a Sanofi Company

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Differentiated Thyroid Cancer
Keywords
vandetanib, AZD 6474, Differentiated Thyroid Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
243 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Vandetanib
Arm Type
Experimental
Arm Description
Vandetanib 300 mg tablet, orally once daily until disease progression or death.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo matched to vandetanib tablet, orally once daily until disease progression or death.
Intervention Type
Drug
Intervention Name(s)
Vandetanib (SAR390530)
Other Intervention Name(s)
CAPRELSA
Intervention Description
Pharmaceutical form: tablet Route of administration: oral
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Pharmaceutical form: tablet Route of administration: oral
Primary Outcome Measure Information:
Title
Progression-Free Survival (PFS)
Description
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.
Time Frame
Randomization until disease progression or death, assessed every 12 weeks (up to 22 months)
Secondary Outcome Measure Information:
Title
Determination of the Efficacy of Vandetanib When Compared to Placebo in the Patient Population as Assessed by Efficacy Variables Including Duration of Response.
Description
Once 155 progression events have occurred.
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
Title
Demonstration of an Improvement in Time to Worsening of Pain in Patients Treated With Vandetanib When Compared to Placebo in the Patient Population.
Description
Once 155 progression events have occurred.
Time Frame
Patient assessments at baseline, week 4, 8, 12 and then every 12 weeks thereafter, assess up to 25.5 months
Title
Evaluation of the Safety and Tolerability of Vandetanib Treatment in the Patient Population by Assessment of Adverse Events, Vital Signs, Laboratory Parameters and Electrocardiography.
Description
Once 155 progression events have occurred.
Time Frame
Safety assessments at baseline, Weeks 1, 2, 4, 8, 12 and then every 12 weeks thereafter
Title
Determination of the Efficacy of Vandetanib When Compared to Placebo in the Patient Population as Assessed by Efficacy Variables Including Objective Response Rate.
Description
Once 155 progression events have occurred.
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
Title
Determination of the Efficacy of Vandetanib When Compared to Placebo in the Patient Population as Assessed by Efficacy Variables Including Change in Tumour Size
Description
Once 155 progression events have occurred.
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.
Title
Determination of the Efficacy of Vandetanib When Compared to Placebo in the Patient Population as Assessed by Efficacy Variables Including Overall Survival
Description
Once 155 progression events have occurred when 25% of randomized patients have died due to any cause.
Time Frame
Estimated time frame at 20 months after initial 25.5 months.
Title
Evaluation of the Pharmacokinetics of Vandetanib in the Patient Population by Assessment of V/F.
Description
Estimated time frame up to 155 progression events have occurred or up to individual progression of patient.
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.
Title
Evaluation of the Pharmacokinetics of Vandetanib in the Patient Population by Assessment of Cmax
Description
Estimated time frame up to 155 progression events have occurred or up to individual progression of patient.
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.
Title
Evaluation of the Pharmacokinetics of Vandetanib in the Patient Population by Assessment of AUCss
Description
Estimated time frame up to 155 progression events have occurred or up to individual progression of patient.
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.
Title
Evaluation of the Pharmacokinetics of Vandetanib in the Patient Population by Assessment of CL/F
Description
Estimated time frame up to 155 progression events have occurred or up to individual progression of patient.
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.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
Research Site
City
Torrance
State/Province
California
ZIP/Postal Code
90502
Country
United States
Facility Name
Research Site
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536-0293
Country
United States
Facility Name
Research Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Research Site
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Washington University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Research Site
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198-4100
Country
United States
Facility Name
Research Site
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Research Site
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Research Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19014
Country
United States
Facility Name
Research Site
City
Porto Alegre
Country
Brazil
Facility Name
Research Site
City
Ribeirão Preto
Country
Brazil
Facility Name
Research Site
City
Rio de Janeiro
Country
Brazil
Facility Name
Research Site
City
São José do Rio Preto
Country
Brazil
Facility Name
Research Site
City
São Paulo
Country
Brazil
Facility Name
Research Site
City
Beijing
Country
China
Facility Name
Research Site
City
Changchun
Country
China
Facility Name
Research Site
City
Chengdu
Country
China
Facility Name
Research Site
City
Huangzhou
Country
China
Facility Name
Research Site
City
Shanghai
Country
China
Facility Name
Research Site
City
Tianjin
Country
China
Facility Name
Research Site
City
Wuhan
Country
China
Facility Name
Research Site
City
Olomouc
Country
Czechia
Facility Name
Research Site
City
Praha
Country
Czechia
Facility Name
Research Site
City
Odense
Country
Denmark
Facility Name
Research Site
City
Angers Cedex 01
Country
France
Facility Name
Research Site
City
Bordeaux Cedex
Country
France
Facility Name
Research Site
City
Caen Cedex 5
Country
France
Facility Name
Research Site
City
Paris Cedex 13
Country
France
Facility Name
Research Site
City
Villejuif Cedex
Country
France
Facility Name
Research Site
City
Catania
Country
Italy
Facility Name
Research Site
City
Milano
Country
Italy
Facility Name
Research Site
City
Napoli
Country
Italy
Facility Name
Research Site
City
Pisa
Country
Italy
Facility Name
Research Site
City
Roma
Country
Italy
Facility Name
Research Site
City
Siena
Country
Italy
Facility Name
Research Site
City
Bunkyo-ku
Country
Japan
Facility Name
Research Site
City
Fukuoka-shi
Country
Japan
Facility Name
Research Site
City
Fukushima-shi
Country
Japan
Facility Name
Research Site
City
Kashiwa-shi
Country
Japan
Facility Name
Research Site
City
Kobe-shi
Country
Japan
Facility Name
Research Site
City
Koto-ku
Country
Japan
Facility Name
Research Site
City
Matsumoto-shi
Country
Japan
Facility Name
Research Site
City
Nagasaki-shi
Country
Japan
Facility Name
Research Site
City
Nagoya-shi
Country
Japan
Facility Name
Research Site
City
Niigata-shi
Country
Japan
Facility Name
Research Site
City
Osaka-shi
Country
Japan
Facility Name
Research Site
City
Shinjuku-ku
Country
Japan
Facility Name
Research Site
City
Yokohama-shi
Country
Japan
Facility Name
Research Site
City
Gliwice
Country
Poland
Facility Name
Research Site
City
Kielce
Country
Poland
Facility Name
Research Site
City
Warszawa
Country
Poland
Facility Name
Research Site
City
Zgierz
Country
Poland
Facility Name
Research Site
City
Barnaul
Country
Russian Federation
Facility Name
Research Site
City
Obninsk
Country
Russian Federation
Facility Name
Research Site
City
Barcelona
Country
Spain
Facility Name
Research Site
City
Gerona
Country
Spain
Facility Name
Research Site
City
Hospitalet de Llobregat(Barcel
Country
Spain
Facility Name
Research Site
City
Madrid
Country
Spain
Facility Name
Research Site
City
Lund
Country
Sweden
Facility Name
Research Site
City
Stockholm
Country
Sweden

12. IPD Sharing Statement

Learn more about this trial

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

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