To Compare The Effects Of Two Doses Of Vandetanib In Patients With Advanced Medullary Thyroid Cancer - Full Text View

Purpose

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.

Condition	Intervention	Phase
Thyroid Cancer	Drug: 300mg vandetanib Drug: 150mg vandetanib	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Thyroid Cancer Thyroid Diseases

Drug Information available for: Thyroid Vandetanib

U.S. FDA Resources

Further study details as provided by AstraZeneca:

Primary Outcome Measures:

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) ] [ Designated as safety issue: No ]
ORR=percentage of patients with a best response of complete or partial response as per Response Evaluation Criteria in Solid Tumors(RECIST)1.1

Secondary Outcome Measures:

Frequency and severity of adverse events by treatment arm [ Time Frame: Treatment period + 60 days up to maximum of 24 months ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
Frequency and severity ophthalmic abnormalities by treatment arm [ Time Frame: Treatment period + 60 days up to maximum of 24 months ] [ Designated as safety issue: Yes ]
Time to objective response (RECIST 1.1) by treatment arm [ Time Frame: Randomization to Week 60 (maximum) ] [ Designated as safety issue: No ]
Duration of objective response (RECIST 1.1) by treatment arm [ Time Frame: Randomization to Week 60 (maximum) ] [ Designated as safety issue: No ]
Best percentage change in sum of target lesion diameters since baseline (RECIST 1.1) by treatment arm [ Time Frame: Randomization to Week 60 (maximum) ] [ Designated as safety issue: No ]
Area under the curve (AUC) of vandetanib in the bloodstream for patients by treatment arm. [ Time Frame: Week 3 to week 60 (maximum) ] [ Designated as safety issue: No ]
Maximum concentration of vandetanib in the bloodstream (Cmax) for patients by treatment arm. [ Time Frame: Week 3 to week 60 (maximum) ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]

Enrollment:	93
Study Start Date:	June 2012
Estimated Study Completion Date:	May 2015
Estimated Primary Completion Date:	June 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 300mg vandetanib	Drug: 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	Drug: 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.

Arms

Assigned Interventions

Active Comparator: 300mg vandetanib

Drug: 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

Drug: 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.

Detailed 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

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01496313

Show 35 Study Locations

Sponsors and Collaborators

AstraZeneca

Investigators

Study Chair:	James Vasselli, MD	AZ MSD
Principal Investigator:	Mimi I Hu, MD	MD Anderson Cancer Centre

More Information

No publications provided

Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT01496313 History of Changes
Other Study ID Numbers:	D4200C00097, 2011-004701-24
Study First Received:	December 2, 2011
Last Updated:	February 28, 2013
Health Authority:	United States: Food and Drug Administration Czech Republic: State Institute for Drug Control Czech Republic: Ethics Committee Germany: Ministry of Health Germany: Ethics Commission India: Drugs Controller General of India India: Institutional Review Board Israel: Ministry of Health Israel: Ethics Commission Italy: Ethics Committee Netherlands: Medical Ethics Review Committee (METC) Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products Poland: Ethics Committee Russia: Ministry of Health of the Russian Federation Russia: FSI Scientific Center of Expertise of Medical Application United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by AstraZeneca:

medullary thyroid cancer
metastatic
thyroid cancer
carcinoma of the thyroid

receptor tyrosine kinase inhibitor
VEGFR
Unresectable locally advanced thyroid cancer

Additional relevant MeSH terms:

Thyroid Neoplasms
Thyroid Diseases
Endocrine Gland Neoplasms
Neoplasms by Site

Neoplasms
Head and Neck Neoplasms
Endocrine System Diseases

ClinicalTrials.gov processed this record on June 18, 2013