Papillary Differentiated Thyroid Cancer, Poorly Differentiated Thyroid Cancer MedDRA version: 19.0 Level: PT Classification code 10071029 Term: Thyroid cancer stage III System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 19.0 Level: PT Classification code 10071030 Term: Thyroid cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 19.0 Level: PT Classifi
Conditions
Interventions
Trade Name: CAPRELSA
Product Name: Caprelsa
Product Code: ZD6474
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: VANDETANIB
CAS Number: 443913-73-3
Current Sponsor code: ZD6474
Concentrat
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion 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 poorly differentiated or papillary thyroid cancer not amenable to surgical resection, external beam radiotherapy or other 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. Patients must have progression and be RAI-refractory/resistant or unsuitable for RAI. TSH suppression below 0.5 mU/L Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 128 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 127
Exclusion criteria
Exclusion criteria: Risk of prolonged QTc as defined by history of QT prolongation; current therapy with any medication known to be associated with Torsades de Pointes or prolongation of QT; congenital long QT syndrome. Previous therapy with approved or investigational tyrosine kinase or anti-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 randomisation Inadequate organ function as defined by elevated ALT, AST, ALP or bilirubin; or creatinine clearance <50 ml/min
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the efficacy (as assessed by progression free survival (PFS) ) of vandetanib when compared to placebo in patients with papillary or poorly differentiated thyroid cancer that is either locally advanced or metastatic who are refractory or unsuitable for radioiodine therapy. ;Secondary Objective: 1. To determine the efficacy of vandetanib when compared to placebo in this patient population as assessed by efficacy variables including duration of response (DOR), objective response rate (ORR), change in tumour size (TS) and overall survival (OS). 2. To evaluate the pharmacokinetics (PK) of vandetanib in this patient population and potentially investigate any influence of patient demography and pathophysiology on vandetanib PK. 3. To demonstrate an improvement in time to worsening of pain (TWP) in patients treated with vandetanib when compared to placebo in this patient population. 4. To evaluate the safety and tolerability of vandetanib treatment in this patient population. ;Primary end point(s): To determine the efficacy (as assessed by progression-free survival) of vandetanib when compared to placebo in the patient population;Timepoint(s) of evaluation of this end point: Once 155 progression events have occurred. This is estimated as 25.5 months (18 months recruitment period plus 7.5 months follow-up). RECIST measurements taken every 12 weeks from randomization. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To determine the efficacy of vandetanib when compared to placebo in the patient population as assessed by efficacy variables including duration of response, objective response rate, change in tumour size and overall survival To evaluate the pharmacokinetics of vandetanib in the patient population by assessment of CL/F, V/F, Cmax and AUCss To demonstrate an improvement in time to worsening of pain in patients treated with vandetanib when compared to placebo in the patient population To evaluate the safety and tolerability of vandetanib treatment in the patient population by assessment of adverse events, vital signs, laboratory parameters and electrocardiographics;Timepoint(s) of evaluation of this end point: Once 155 progression events have occurred. Analysis of overall survival to be repeated when 50% of randomised patients have died due to any cause. Estimated at 20 months after initial 25.5 months Blood sampling at 4-6 hours post-dose at Weeks 1, 2, 4, 8, 12 and then 12 weekly thereafter until discontinuation Once 155 progression events have occurred. Patient assessments at baseline, week 4, 8, 12 and then 12 weekly thereafter Once 155 progression events have occurred. Safety assessments at baseline, Weeks 1, 2, 4, 8, 12 and then 12 weekly thereafter | — |
Countries
Brazil, China, Czech Republic, Denmark, France, Italy, Japan, Poland, Russian Federation, Spain, Sweden, United States
Contacts
Public ContactInformation Centre
AstraZeneca
Outcome results
None listed