To Compare The Effects Of Two Doses Of Vandetanib In Patients With Advanced Medullary Thyroid Cancer

• ClinicalTrials.gov Identifier: NCT01496313
• Recruitment Status: Active, not recruiting
• First Posted: December 21, 2011
• Results First Posted: November 27, 2015
• Last Update Posted: March 4, 2020
• Sponsor: Genzyme, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Genzyme, a Sanofi Company )

Tracking Information

• First Submitted Date: December 2, 2011
• First Posted Date: December 21, 2011
• Results First Submitted Date: April 1, 2015
• Results First Posted Date: November 27, 2015
• Last Update Posted Date: March 4, 2020
• Study Start Date: June 2012
• Actual Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 27, 2015)

Overall Response Rate (ORR) for Vandetanib 150 and 300mg With Responses Determined by the Investigator [ Time Frame: Randomisation to week 60 (maximum) ]

ORR=proportion of patients with a best response of complete or partial response as per Response Evaluation Criteria in Solid Tumors(RECIST)1.1

Original Primary Outcome Measures (submitted: December 19, 2011)

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) ]

ORR=percentage of patients with a best response of complete or partial response as per Response Evaluation Criteria in Solid Tumors(RECIST)1.1

Current Secondary Outcome Measures (submitted: October 27, 2015)

• Best Objective Response [ Time Frame: Randomisation to week 60 (maximum) ]
• Duration of Objective Response (RECIST 1.1) by Treatment Arm [ Time Frame: Randomization to Week 60 (maximum) ]
• Time to Objective Response (RECIST 1.1) by Treatment Arm [ Time Frame: Randomization to Week 60 (maximum) ]
• Percentage Change From Baseline in Target Lesion Size (RECIST 1.1) by Treatment Arm [ Time Frame: Randomization to Week 60 (maximum) ]
• Plasma Concentration of Vandetanib in the Bloodstream (Cmax) for Patients by Treatment Arm. [ Time Frame: Week 3 to week 60 (maximum) ]

Original Secondary Outcome Measures (submitted: December 19, 2011)

• 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 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: To Compare The Effects Of Two Doses Of Vandetanib In Patients With Advanced Medullary Thyroid Cancer
• 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
• Brief 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.
• 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
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Thyroid Cancer

Intervention

• 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.

  Other Name: SAR390530
• 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.

  Other Name: SAR390530

Study Arms

• Active Comparator: 300mg vandetanib
  Intervention: Drug: 300mg vandetanib
• Active Comparator: 150mg vandetanib
  Intervention: Drug: 150mg vandetanib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: October 11, 2016): 81
• Original Estimated Enrollment (submitted: December 19, 2011): 80
• Estimated Study Completion Date: December 30, 2020
• Actual Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Czechia, India, Israel, Italy, Netherlands, Poland, Russian Federation, United Kingdom, United States
• Removed Location Countries: Czech Republic, Germany, Taiwan

Administrative Information

• NCT Number: NCT01496313
• Other Study ID Numbers: D4200C00097; 2011-004701-24 ( EudraCT Number ); LPS14809 ( Other Identifier: Sanofi )
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Sanofi ( Genzyme, a Sanofi Company )
• Study Sponsor: Genzyme, a Sanofi Company
• Collaborators: Not Provided

Investigators

• Study Chair: Clinical Sciences & Operations; Sanofi

• PRS Account: Sanofi
• Verification Date: February 2020