Neoplasms

Gland and Hormone Related Diseases

All Conditions

Thyroid Neoplasms

Thyroid Diseases

Endocrine System Diseases

Endocrine Gland Neoplasms

Head and Neck Neoplasms

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.

Pharmaceutical form: tablet

Route of administration: oral

Vandetanib (SAR390530)

Placebo

Clinical Sciences & Operations

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.

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.

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

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.

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.

Once 155 progression events have occurred.

Once 155 progression events have occurred when 25% of randomized patients have died due to any cause.

Estimated time frame up to 155 progression events have occurred or up to individual progression of patient.

Genzyme, a Sanofi Company

Reported AEs are treatment-emergent adverse events, i.e., AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 60 days after the last administration of study drug). Analysis was performed on the safety population, which included all participants who received at least one dose of randomized treatment.

Vandetanib

Total

Age, Continuous

Sex: Female, Male

Trial Transparency Team

A multiple testing procedure (MTP) with an alpha-exhaustive recycling strategy was employed to provide adequate control of type I error.

Intent to treat population included all randomized participants.

Progression-Free Survival (PFS)

Determination of the Efficacy of Vandetanib When Compared to Placebo in the Patient Population as Assessed by Efficacy Variables Including Duration of Response.

Demonstration of an Improvement in Time to Worsening of Pain in Patients Treated With Vandetanib When Compared to Placebo in the Patient Population.

Evaluation of the Safety and Tolerability of Vandetanib Treatment in the Patient Population by Assessment of Adverse Events, Vital Signs, Laboratory Parameters and Electrocardiography.

Determination of the Efficacy of Vandetanib When Compared to Placebo in the Patient Population as Assessed by Efficacy Variables Including Objective Response Rate.

Determination of the Efficacy of Vandetanib When Compared to Placebo in the Patient Population as Assessed by Efficacy Variables Including Change in Tumour Size

Determination of the Efficacy of Vandetanib When Compared to Placebo in the Patient Population as Assessed by Efficacy Variables Including Overall Survival

Spots Global Cancer Trial Database for vandetanib (sar390530)