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

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ClinicalTrials.gov Identifier: NCT01876784
Recruitment Status : Active, not recruiting
First Posted : June 13, 2013
Results First Posted : March 13, 2017
Last Update Posted : April 9, 2021
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Differentiated Thyroid Cancer
Interventions Drug: Vandetanib (SAR390530)
Drug: Placebo
Enrollment 243
Recruitment Details The study was conducted at 66 centers in 12 countries. A total of 299 participants were screened between 17 September 2013 and 26 September 2014 of whom 238 participants were randomized and 235 were treated.
Pre-assignment Details  
Arm/Group Title Vandetanib Placebo
Hide Arm/Group Description 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.
Period Title: Overall Study
Started 119 119
Treated 117 118
Completed 0 0
Not Completed 119 119
Reason Not Completed
Withdrawal by Subject             17             2
Adverse Event             15             2
Protocol Violation             1             0
Disease progression             37             67
Lost to Follow-up             0             1
Death             1             0
Randomized but not treated             2             1
Other than specified above             5             6
Ongoing             41             40
Arm/Group Title Vandetanib Placebo Total
Hide Arm/Group Description 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. Total of all reporting groups
Overall Number of Baseline Participants 119 119 238
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 119 participants 119 participants 238 participants
64.2  (9.69) 63.2  (11.02) 63.7  (10.36)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 119 participants 119 participants 238 participants
Female
70
  58.8%
64
  53.8%
134
  56.3%
Male
49
  41.2%
55
  46.2%
104
  43.7%
1.Primary Outcome
Title Progression-Free Survival (PFS)
Hide Description 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.
Time Frame Randomization until disease progression or death, assessed every 12 weeks (up to 22 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat population included all randomized participants.
Arm/Group Title Vandetanib Placebo
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 119 119
Median (95% Confidence Interval)
Unit of Measure: months
10.0
(6.0 to 11.1)
5.7
(5.5 to 8.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vandetanib, Placebo
Comments A multiple testing procedure (MTP) with an alpha-exhaustive recycling strategy was employed to provide adequate control of type I error.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.080
Comments Threshold for significance at 0.05 level.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.75
Confidence Interval (2-Sided) 95%
0.55 to 1.03
Estimation Comments Vandetanib 300 mg vs Placebo
2.Secondary Outcome
Title Determination of the Efficacy of Vandetanib When Compared to Placebo in the Patient Population as Assessed by Efficacy Variables Including Duration of Response.
Hide Description Once 155 progression events have occurred.
Time Frame Estimated time frame up to 25.5 months (18 months recruitment period plus 7.5 months follow up). RECIST measurements taken every 12 weeks from randomization
Outcome Measure Data Not Reported
3.Secondary Outcome
Title Demonstration of an Improvement in Time to Worsening of Pain in Patients Treated With Vandetanib When Compared to Placebo in the Patient Population.
Hide Description Once 155 progression events have occurred.
Time Frame Patient assessments at baseline, week 4, 8, 12 and then every 12 weeks thereafter, assess up to 25.5 months
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Evaluation of the Safety and Tolerability of Vandetanib Treatment in the Patient Population by Assessment of Adverse Events, Vital Signs, Laboratory Parameters and Electrocardiography.
Hide Description Once 155 progression events have occurred.
Time Frame Safety assessments at baseline, Weeks 1, 2, 4, 8, 12 and then every 12 weeks thereafter
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Determination of the Efficacy of Vandetanib When Compared to Placebo in the Patient Population as Assessed by Efficacy Variables Including Objective Response Rate.
Hide Description Once 155 progression events have occurred.
Time Frame Estimated time frame up to 25.5 months (18 months recruitment period plus 7.5 months follow up). RECIST measurements taken every 12 weeks from randomization
Outcome Measure Data Not Reported
6.Secondary Outcome
Title Determination of the Efficacy of Vandetanib When Compared to Placebo in the Patient Population as Assessed by Efficacy Variables Including Change in Tumour Size
Hide Description Once 155 progression events have occurred.
Time Frame Assessed tumour size at screening, Weeks 7, 8 and then every 12 weeks thereafter and at Discontinuation visit, estimated time frame at 25.5 months.
Outcome Measure Data Not Reported
7.Secondary Outcome
Title Determination of the Efficacy of Vandetanib When Compared to Placebo in the Patient Population as Assessed by Efficacy Variables Including Overall Survival
Hide Description Once 155 progression events have occurred when 25% of randomized patients have died due to any cause.
Time Frame Estimated time frame at 20 months after initial 25.5 months.
Outcome Measure Data Not Reported
8.Secondary Outcome
Title Evaluation of the Pharmacokinetics of Vandetanib in the Patient Population by Assessment of V/F.
Hide Description Estimated time frame up to 155 progression events have occurred or up to individual progression of patient.
Time Frame Blood sampling at 4-6 hours post-dose at Weeks 1, 2, 4, 8, 12 and then every 12 weeks thereafter until discontinuation.
Outcome Measure Data Not Reported
9.Secondary Outcome
Title Evaluation of the Pharmacokinetics of Vandetanib in the Patient Population by Assessment of Cmax
Hide Description Estimated time frame up to 155 progression events have occurred or up to individual progression of patient.
Time Frame Blood sampling at 4-6 hours post-dose at Weeks 1, 2, 4, 8, 12 and then every 12 weeks thereafter until discontinuation.
Outcome Measure Data Not Reported
10.Secondary Outcome
Title Evaluation of the Pharmacokinetics of Vandetanib in the Patient Population by Assessment of AUCss
Hide Description Estimated time frame up to 155 progression events have occurred or up to individual progression of patient.
Time Frame Blood sampling at 4-6 hours post-dose at Weeks 1, 2, 4, 8, 12 and then every 12 weeks thereafter until discontinuation.
Outcome Measure Data Not Reported
11.Secondary Outcome
Title Evaluation of the Pharmacokinetics of Vandetanib in the Patient Population by Assessment of CL/F
Hide Description Estimated time frame up to 155 progression events have occurred or up to individual progression of patient.
Time Frame Blood sampling at 4-6 hours post-dose at Weeks 1, 2, 4, 8, 12 and then every 12 weeks thereafter until discontinuation.
Outcome Measure Data Not Reported
Time Frame All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 22 months) regardless of seriousness or relationship to investigational product
Adverse Event Reporting Description 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.
 
Arm/Group Title Vandetanib Placebo
Hide Arm/Group Description 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.
All-Cause Mortality
Vandetanib Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Vandetanib Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   29/117 (24.79%)   15/118 (12.71%) 
Blood and lymphatic system disorders     
Anaemia  1  0/117 (0.00%)  1/118 (0.85%) 
Thrombocytopenia  1  1/117 (0.85%)  2/118 (1.69%) 
Cardiac disorders     
Atrial fibrillation  1  0/117 (0.00%)  1/118 (0.85%) 
Cardiac arrest  1  1/117 (0.85%)  0/118 (0.00%) 
Cardiac failure  1  0/117 (0.00%)  1/118 (0.85%) 
Ventricular extrasystoles  1  1/117 (0.85%)  0/118 (0.00%) 
Endocrine disorders     
Inappropriate antidiuretic hormone secretion  1  1/117 (0.85%)  0/118 (0.00%) 
Gastrointestinal disorders     
Diarrhoea  1  3/117 (2.56%)  1/118 (0.85%) 
Dysphagia  1  0/117 (0.00%)  2/118 (1.69%) 
Large intestine polyp  1  1/117 (0.85%)  0/118 (0.00%) 
General disorders     
Multi-organ failure  1  1/117 (0.85%)  0/118 (0.00%) 
Infections and infestations     
Lung infection  1  2/117 (1.71%)  0/118 (0.00%) 
Pneumonia  1  3/117 (2.56%)  2/118 (1.69%) 
Pyelonephritis  1  0/117 (0.00%)  1/118 (0.85%) 
Respiratory tract infection  1  1/117 (0.85%)  0/118 (0.00%) 
Sepsis  1  1/117 (0.85%)  0/118 (0.00%) 
Viral upper respiratory tract infection  1  1/117 (0.85%)  0/118 (0.00%) 
Injury, poisoning and procedural complications     
Femur fracture  1  0/117 (0.00%)  1/118 (0.85%) 
Post procedural haemorrhage  1  1/117 (0.85%)  0/118 (0.00%) 
Investigations     
Blood creatinine increased  1  0/117 (0.00%)  1/118 (0.85%) 
Troponin increased  1  1/117 (0.85%)  0/118 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite  1  1/117 (0.85%)  0/118 (0.00%) 
Hypercalcaemia  1  0/117 (0.00%)  1/118 (0.85%) 
Musculoskeletal and connective tissue disorders     
Musculoskeletal chest pain  1  1/117 (0.85%)  0/118 (0.00%) 
Pathological fracture  1  1/117 (0.85%)  0/118 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Bladder cancer  1  1/117 (0.85%)  0/118 (0.00%) 
Colon cancer  1  0/117 (0.00%)  1/118 (0.85%) 
Leukaemia  1  0/117 (0.00%)  1/118 (0.85%) 
Nervous system disorders     
Cerebrovascular accident  1  1/117 (0.85%)  0/118 (0.00%) 
Dizziness  1  1/117 (0.85%)  0/118 (0.00%) 
Generalised tonic-clonic seizure  1  1/117 (0.85%)  0/118 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure  1  0/117 (0.00%)  1/118 (0.85%) 
Dyspnoea  1  1/117 (0.85%)  3/118 (2.54%) 
Haemoptysis  1  1/117 (0.85%)  0/118 (0.00%) 
Interstitial lung disease  1  1/117 (0.85%)  0/118 (0.00%) 
Pleural effusion  1  1/117 (0.85%)  0/118 (0.00%) 
Pneumonia aspiration  1  1/117 (0.85%)  0/118 (0.00%) 
Pneumothorax  1  1/117 (0.85%)  0/118 (0.00%) 
Pulmonary embolism  1  1/117 (0.85%)  0/118 (0.00%) 
Respiratory failure  1  2/117 (1.71%)  0/118 (0.00%) 
Skin and subcutaneous tissue disorders     
Photosensitivity reaction  1  1/117 (0.85%)  0/118 (0.00%) 
Rash  1  1/117 (0.85%)  0/118 (0.00%) 
Stevens-Johnson syndrome  1  1/117 (0.85%)  0/118 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (18.1)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Vandetanib Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   113/117 (96.58%)   100/118 (84.75%) 
Blood and lymphatic system disorders     
Anaemia  1  2/117 (1.71%)  6/118 (5.08%) 
Eye disorders     
Keratopathy  1  6/117 (5.13%)  0/118 (0.00%) 
Gastrointestinal disorders     
Abdominal pain  1  8/117 (6.84%)  7/118 (5.93%) 
Constipation  1  9/117 (7.69%)  9/118 (7.63%) 
Diarrhoea  1  78/117 (66.67%)  23/118 (19.49%) 
Dyspepsia  1  6/117 (5.13%)  3/118 (2.54%) 
Nausea  1  18/117 (15.38%)  15/118 (12.71%) 
Stomatitis  1  6/117 (5.13%)  3/118 (2.54%) 
Vomiting  1  9/117 (7.69%)  10/118 (8.47%) 
General disorders     
Asthenia  1  19/117 (16.24%)  11/118 (9.32%) 
Fatigue  1  13/117 (11.11%)  12/118 (10.17%) 
Pyrexia  1  5/117 (4.27%)  9/118 (7.63%) 
Infections and infestations     
Nasopharyngitis  1  7/117 (5.98%)  7/118 (5.93%) 
Upper respiratory tract infection  1  4/117 (3.42%)  8/118 (6.78%) 
Urinary tract infection  1  9/117 (7.69%)  3/118 (2.54%) 
Investigations     
Alanine aminotransferase increased  1  16/117 (13.68%)  3/118 (2.54%) 
Aspartate aminotransferase increased  1  15/117 (12.82%)  3/118 (2.54%) 
Blood creatinine increased  1  7/117 (5.98%)  1/118 (0.85%) 
Electrocardiogram QT prolonged  1  34/117 (29.06%)  3/118 (2.54%) 
Weight decreased  1  8/117 (6.84%)  3/118 (2.54%) 
Metabolism and nutrition disorders     
Decreased appetite  1  19/117 (16.24%)  2/118 (1.69%) 
Hypocalcaemia  1  14/117 (11.97%)  3/118 (2.54%) 
Hypokalaemia  1  9/117 (7.69%)  5/118 (4.24%) 
Hypomagnesaemia  1  9/117 (7.69%)  1/118 (0.85%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  7/117 (5.98%)  4/118 (3.39%) 
Back pain  1  5/117 (4.27%)  9/118 (7.63%) 
Musculoskeletal chest pain  1  7/117 (5.98%)  8/118 (6.78%) 
Musculoskeletal pain  1  0/117 (0.00%)  8/118 (6.78%) 
Nervous system disorders     
Headache  1  12/117 (10.26%)  9/118 (7.63%) 
Psychiatric disorders     
Insomnia  1  15/117 (12.82%)  2/118 (1.69%) 
Renal and urinary disorders     
Proteinuria  1  7/117 (5.98%)  0/118 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  10/117 (8.55%)  11/118 (9.32%) 
Dyspnoea  1  5/117 (4.27%)  7/118 (5.93%) 
Haemoptysis  1  4/117 (3.42%)  6/118 (5.08%) 
Oropharyngeal pain  1  3/117 (2.56%)  6/118 (5.08%) 
Skin and subcutaneous tissue disorders     
Acne  1  9/117 (7.69%)  2/118 (1.69%) 
Dermatitis acneiform  1  12/117 (10.26%)  2/118 (1.69%) 
Dry skin  1  15/117 (12.82%)  5/118 (4.24%) 
Erythema  1  6/117 (5.13%)  1/118 (0.85%) 
Palmar-plantar erythrodysaesthesia syndrome  1  6/117 (5.13%)  0/118 (0.00%) 
Photosensitivity reaction  1  13/117 (11.11%)  0/118 (0.00%) 
Pruritus  1  7/117 (5.98%)  7/118 (5.93%) 
Rash  1  40/117 (34.19%)  7/118 (5.93%) 
Rash maculo-papular  1  7/117 (5.98%)  1/118 (0.85%) 
Vascular disorders     
Hypertension  1  47/117 (40.17%)  7/118 (5.93%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (18.1)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Trial Transparency Team
Organization: Sanofi
EMail: Contact-US@sanofi.com
Layout table for additonal information
Responsible Party: Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT01876784    
Other Study ID Numbers: D4203C00011
2013-000422-58 ( EudraCT Number )
LPS14813 ( Other Identifier: Sanofi )
First Submitted: June 11, 2013
First Posted: June 13, 2013
Results First Submitted: January 23, 2017
Results First Posted: March 13, 2017
Last Update Posted: April 9, 2021