Clinical trial NCT01876784: Evaluation of Efficacy, Safety of Vandetanib in Patients With Differentiated Thyroid Cancer
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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Differentiated Thyroid Cancer
Keywords: vandetanib, AZD 6474, Differentiated Thyroid Cancer
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2013-06-13
Enrollment: 238
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 received vandetanib as randomized treatment were allowed, upon re-consent, to continue on open-label vandetanib if in the opinion of the Investigator the participant received benefit. Placebo participants who experienced disease progression within 60 days of unblinding were offered the option of treatment with open-label vandetanib if, in the Investigator's opinion, such treatment was of clinical benefit to the participant. Approximately 2 years; duration depends on individual participant response.

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 tumor 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 randomization, 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 Organization (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\*upper limit of normal (ULN), or greater than 5.0\*ULN if judged by the Investigator to be related to liver metastases. (2) Serum bilirubin greater than 1.5\*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.

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Randomization until disease progression or death, assessed every 12 weeks (up to 22 months)
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From randomization to the date of death due to any cause (maximum duration: up to 42 months)
measure: Randomized Treatment Period: Percent Change From Baseline in Tumor Size (TS) at Week 36
timeFrame: Baseline, Week 36
measure: Percentage of Participants With Objective Response
timeFrame: From randomization to the date of first documented tumor progression, or death due to any cause, whichever comes first (maximum duration: up to 42 months)
measure: Time to Worsening of Pain (TWP) Using Numeric Rating Scale (NRS) of Worst Pain
timeFrame: From randomization to the date of first assessment of worsening of pain (maximum duration: up to 42 months)
measure: Duration of Response (DOR)
timeFrame: From the date of first response to the date of first documented tumor progression or death due to any cause whichever comes first (maximum duration: up to 42 months)
measure: Randomized Treatment Period: PK Parameters: Maximum Plasma Concentration (Cmax)
timeFrame: Post-dose on Week 1 to Week 48
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Research Site
state: Arkansas
city: Torrance
country: United States
facility: Research Site
state: California
city: Lexington
country: United States
facility: Research Site
state: Kentucky
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Research Site
state: Michigan
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Omaha
country: United States
facility: Research Site
state: Nebraska
city: New York
country: United States
facility: Research Site
state: New York
city: Portland
country: United States
facility: Research Site
state: Oregon
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Porto Alegre
country: Brazil
facility: Research Site
city: Ribeirão Preto
country: Brazil
facility: Research Site
city: Rio de Janeiro
country: Brazil
facility: Research Site
city: São José do Rio Preto
country: Brazil
facility: Research Site
city: São Paulo
country: Brazil
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Changchun
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Huangzhou
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Tianjin
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Olomouc
country: Czechia
facility: Research Site
city: Praha
country: Czechia
facility: Research Site
city: Odense
country: Denmark
facility: Research Site
city: Angers Cedex 01
country: France
facility: Research Site
city: Bordeaux Cedex
country: France
facility: Research Site
city: Caen Cedex 5
country: France
facility: Research Site
city: Paris Cedex 13
country: France
facility: Research Site
city: Villejuif Cedex
country: France
facility: Research Site
city: Catania
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Napoli
country: Italy
facility: Research Site
city: Pisa
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Siena
country: Italy
facility: Research Site
city: Bunkyo-ku
country: Japan
facility: Research Site
city: Fukuoka-shi
country: Japan
facility: Research Site
city: Fukushima-shi
country: Japan
facility: Research Site
city: Kashiwa-shi
country: Japan
facility: Research Site
city: Kobe-shi
country: Japan
facility: Research Site
city: Koto-ku
country: Japan
facility: Research Site
city: Matsumoto-shi
country: Japan
facility: Research Site
city: Nagasaki-shi
country: Japan
facility: Research Site
city: Nagoya-shi
country: Japan
facility: Research Site
city: Niigata-shi
country: Japan
facility: Research Site
city: Osaka-shi
country: Japan
facility: Research Site
city: Shinjuku-ku
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
city: Gliwice
country: Poland
facility: Research Site
city: Kielce
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Zgierz
country: Poland
facility: Research Site
city: Barnaul
country: Russian Federation
facility: Research Site
city: Obninsk
country: Russian Federation
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Gerona
country: Spain
facility: Research Site
city: Hospitalet de Llobregat(Barcel
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Lund
country: Sweden
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: