Overview

This trial is active, not recruiting.

Condition thyroid cancer
Treatments 300mg vandetanib, 150mg vandetanib
Phase phase 4
Sponsor AstraZeneca
Start date June 2012
End date April 2014
Trial size 93 participants
Trial identifier NCT01496313, 2011-004701-24, D4200C00097

Summary

The purpose of this study is to give patients with medullary thyroid cancer either 300mg/day or 150mg/day vandetanib and compare how well each dose affects how their cancer responds. It will also help the investigators understand the side effects of different doses in these patients.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator)
Primary purpose treatment
Arm
(Active Comparator)
300mg vandetanib
Oral blinded tablets taken once daily. At objective disease progression or 14 months (whichever is earlier), patient may be unblinded to treatment Dosing with unblinded study treatment can continue until 24 months after patient was randomised. At any time dosing may be interrupted for up to 6 weeks due to toxicity. Dosing may restart at a reduced dose (200mg/day). Once reduced, dose increases are not permitted and dosing must stop if further toxicities occur.
(Active Comparator)
150mg vandetanib
Oral blinded tablets taken once daily. At objective disease progression or 14 months (whichever is earlier), patient may be unblinded to treatment. Patients who have not dose reduced at the time of unblinding may have their dose increased to 300mg Dosing with unblinded study treatment can continue until 24 months after patient was randomised At any time dosing may be interrupted for up to 6 weeks due to toxicity. Dosing may restart at a reduced dose (100mg/day) [OR 300 reduced to 200mg/day if dose was increased at unblinding.] Once reduced, dose increases are not permitted and dosing must stop if further toxicities occur.

Primary Outcomes

Measure
Change from baseline, overall response rate (ORR) for vandetanib 150 and 300mg with responses determined by the Investigator
time frame: Randomisation to week 60 (maximum)

Secondary Outcomes

Measure
Frequency and severity of adverse events by treatment arm
time frame: Treatment period + 60 days up to maximum of 24 months
Frequency and severity of clinically significant results for blood pressure by treatment arm
time frame: Treatment period + 60 days up to maximum of 24 months
Frequency and severity of clinically significant results for QTc prolongation by treatment arm
time frame: Treatment period + 60 days up to maximum of 24 months
Frequency and severity of clinically significant results for cardiac ejection fraction by treatment arm
time frame: Treatment period + 60 days up to maximum of 24 months
Frequency and severity of clinically significant results for laboratory findings by treatment arm
time frame: Treatment period + 60 days up to maximum of 24 months
Frequency and severity ophthalmic abnormalities by treatment arm
time frame: Treatment period + 60 days up to maximum of 24 months
Time to objective response (RECIST 1.1) by treatment arm
time frame: Randomization to Week 60 (maximum)
Duration of objective response (RECIST 1.1) by treatment arm
time frame: Randomization to Week 60 (maximum)
Best percentage change in sum of target lesion diameters since baseline (RECIST 1.1) by treatment arm
time frame: Randomization to Week 60 (maximum)
Area under the curve (AUC) of vandetanib in the bloodstream for patients by treatment arm.
time frame: Week 3 to week 60 (maximum)
Maximum concentration of vandetanib in the bloodstream (Cmax) for patients by treatment arm.
time frame: Week 3 to week 60 (maximum)
Area under the curve (AUC) of vandetanib in the bloodstream when QT interval corrected for heart rate according to Fridericia (QTcF) >=500milliseconds by treatment arm
time frame: Treatment period + 60 days up to maximum of 24 months
Maximum concentration (Cmax) of vandetanib in the bloodstream when QT interval corrected for heart rate according to Fridericia (QTcF) >=500milliseconds by treatment arm
time frame: Treatment period + 60 days up to maximum of 24 months

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Written consent from Female or male patients aged 18 years and over. Previously confirmed histological diagnosis of unresectable, locally advanced or metastatic, hereditary or sporadic MTC Objective disease progression within the previous 14 months prior to enrolment, and/or - Have one or more symptoms that the Investigator believes to be related to the patient's MTC. - World Health Organisation (WHO) or Eastern Cooperative Oncology Group (ECOG) Performance status 0-2. - Has measurable disease (at least one lesion, not irradiated within 12 weeks of study randomisation, with longest diameter more or equal 10mm (lymph nodes minimum more or equal 15 mm) with CT or MRI). - Lesions must be amenable to accurate and repeat measurement. Exclusion Criteria: - Prior treatment (major surgery, radiation therapy, chemotherapy, or other investigational drugs) received within 28 days before randomization. - Abnormal liver function tests (bilirubin more than 1.5xULRR, and ALT, AST, or ALP more than 2.5xULRR or 5.0xULRR if related to liver metastases). - Significant cardiac conditions or events such as reduced cardiac functions, symptomatic cardiac arrhythmia requiring treatment, congenital long QT syndrome, history of drug-induced QT prolongation, or QTcF correction unmeasurable or more than 450 ms. - Abnormal electrolytes such as potassium, magnesium and calcium, or abnormal organ functions such as decreased creatinine clearance. - For women only - currently pregnant or breast feeding.

Additional Information

Official title An International, Randomised, Double-Blind, Two-Arm Study To Evaluate The Safety And Efficacy Of Vandetanib 150 And 300mg/Day In Patients With Unresectable Locally Advanced Or Metastatic Medullary Thyroid Carcinoma With Progressive Or Symptomatic Disease
Principal investigator Mimi I Hu, MD
Description An International, Randomised, Double-Blind, Two-Arm Study To Evaluate The Safety And Efficacy Of Vandetanib 150 And 300mg/Day In Patients With Unresectable Locally Advanced Or Metastatic Medullary Thyroid Carcinoma With Progressive Or Symptomatic Disease
Trial information was received from ClinicalTrials.gov and was last updated in October 2014.
Information provided to ClinicalTrials.gov by AstraZeneca.