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

Differentiated Thyroid Cancer Clinical Trial

— 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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01876784
• Other study ID #: D4203C00011
• Secondary ID: 2013-000422-58LP
• Status: Completed
• Phase: Phase 3
• Start date: September 17, 2013
• Est. completion date: January 22, 2022

Study information

• Verified date: January 2023
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 243
• Est. completion date: January 22, 2022
• Est. primary completion date: August 30, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Differentiated Thyroid Cancer
• Thyroid Diseases
• Thyroid Neoplasms

Intervention

Drug:
• Vandetanib (SAR390530)
Pharmaceutical form: tablet Route of administration: oral
• Placebo
Pharmaceutical form: tablet Route of administration: oral

Locations

Country	Name	City	State
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Ribeirão Preto
Brazil	Research Site	Rio de Janeiro
Brazil	Research Site	São José do Rio Preto
Brazil	Research Site	São Paulo
China	Research Site	Beijing
China	Research Site	Changchun
China	Research Site	Chengdu
China	Research Site	Huangzhou
China	Research Site	Shanghai
China	Research Site	Tianjin
China	Research Site	Wuhan
Czechia	Research Site	Olomouc
Czechia	Research Site	Praha
Denmark	Research Site	Odense
France	Research Site	Angers Cedex 01
France	Research Site	Bordeaux Cedex
France	Research Site	Caen Cedex 5
France	Research Site	Paris Cedex 13
France	Research Site	Villejuif Cedex
Italy	Research Site	Catania
Italy	Research Site	Milano
Italy	Research Site	Napoli
Italy	Research Site	Pisa
Italy	Research Site	Roma
Italy	Research Site	Siena
Japan	Research Site	Bunkyo-ku
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Fukushima-shi
Japan	Research Site	Kashiwa-shi
Japan	Research Site	Kobe-shi
Japan	Research Site	Koto-ku
Japan	Research Site	Matsumoto-shi
Japan	Research Site	Nagasaki-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Niigata-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Shinjuku-ku
Japan	Research Site	Yokohama-shi
Poland	Research Site	Gliwice
Poland	Research Site	Kielce
Poland	Research Site	Warszawa
Poland	Research Site	Zgierz
Russian Federation	Research Site	Barnaul
Russian Federation	Research Site	Obninsk
Spain	Research Site	Barcelona
Spain	Research Site	Gerona
Spain	Research Site	Hospitalet de Llobregat(Barcel
Spain	Research Site	Madrid
Sweden	Research Site	Lund
Sweden	Research Site	Stockholm
United States	Research Site	Ann Arbor	Michigan
United States	Research Site	Boston	Massachusetts
United States	Research Site	Lexington	Kentucky
United States	Research Site	Little Rock	Arkansas
United States	Research Site	New York	New York
United States	Research Site	Omaha	Nebraska
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Portland	Oregon
United States	Washington University	Saint Louis	Missouri
United States	Research Site	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
Genzyme, a Sanofi Company

Countries where clinical trial is conducted

United States,  Brazil,  China,  Czechia,  Denmark,  France,  Italy,  Japan,  Poland,  Russian Federation,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Randomization until disease progression or death, assessed every 12 weeks (up to 22 months)
Secondary	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.	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
Secondary	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.	Patient assessments at baseline, week 4, 8, 12 and then every 12 weeks thereafter, assess up to 25.5 months
Secondary	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.	Safety assessments at baseline, Weeks 1, 2, 4, 8, 12 and then every 12 weeks thereafter
Secondary	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.	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
Secondary	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.	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.
Secondary	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.	Estimated time frame at 20 months after initial 25.5 months.
Secondary	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.	Blood sampling at 4-6 hours post-dose at Weeks 1, 2, 4, 8, 12 and then every 12 weeks thereafter until discontinuation.
Secondary	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.	Blood sampling at 4-6 hours post-dose at Weeks 1, 2, 4, 8, 12 and then every 12 weeks thereafter until discontinuation.
Secondary	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.	Blood sampling at 4-6 hours post-dose at Weeks 1, 2, 4, 8, 12 and then every 12 weeks thereafter until discontinuation.
Secondary	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.	Blood sampling at 4-6 hours post-dose at Weeks 1, 2, 4, 8, 12 and then every 12 weeks thereafter until discontinuation.