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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier:
NCT01876784
First received: June 11, 2013
Last updated: January 23, 2017
Last verified: January 2017
  Purpose

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.

Condition Intervention Phase
Differentiated Thyroid Cancer
Drug: Vandetanib (SAR390530)
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Investigator, Outcomes Assessor
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • 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.


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. [ 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.


Enrollment: 238
Study Start Date: September 2013
Estimated Study Completion Date: December 2019
Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vandetanib
Vandetanib 300 mg tablet, orally once daily until disease progression or death.
Drug: Vandetanib (SAR390530)

Pharmaceutical form: tablet

Route of administration: oral

Other Name: CAPRELSA
Placebo Comparator: Placebo
Placebo matched to vandetanib tablet, orally once daily until disease progression or death.
Drug: Placebo

Pharmaceutical form: tablet

Route of administration: oral


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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  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: NCT01876784

  Show 61 Study Locations
Sponsors and Collaborators
Genzyme, a Sanofi Company
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

Responsible Party: Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier: NCT01876784     History of Changes
Other Study ID Numbers: D4203C00011
2013-000422-58 ( EudraCT Number )
LPS14813 ( Other Identifier: Sanofi )
Study First Received: June 11, 2013
Results First Received: January 23, 2017
Last Updated: January 23, 2017

Keywords provided by Sanofi:
vandetanib, AZD 6474, Differentiated Thyroid Cancer

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 March 23, 2017