Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    D4200C00072
Previous Study | Return to List | Next Study

Phase II Study of Best Support Care (BSC) Plus ZD6474(Vandetanib) in Patients With Inoperable Hepatocellular Carcinoma (HCC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00508001
Recruitment Status : Completed
First Posted : July 27, 2007
Results First Posted : July 17, 2012
Last Update Posted : October 10, 2016
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Carcinoma, Hepatocellular
Interventions Drug: Vandetanib
Drug: Best Supportive Care
Enrollment 67
Recruitment Details 78 patients were recruited at medical clinic
Pre-assignment Details 11 patients were screening failure due to inclusion criteria or exclusion criteria is not fulfilled
Arm/Group Title ZD6474 300 ZD6474 100 Placebo
Hide Arm/Group Description ZD6474 (Vandetanib) 300 mg ( one tablet per day, orally). plus Best Support Care ZD6474 (Vandetanib) 100 mg (one tablet per day, orally). plus Best Support Care Placebo plus Best Support Care
Period Title: Overall Study
Started 19 25 23
Secondary Treatment Phase 0 13 16
Completed 0 13 16
Not Completed 19 12 7
Reason Not Completed
Adverse Event             2             0             4
condition under investigation worsened             13             7             1
Death             0             1             1
Withdrawal by Subject             4             4             1
Arm/Group Title ZD6474 300 ZD6474 100 Placebo Total
Hide Arm/Group Description ZD6474 (Vandetanib) 300 mg ( one tablet per day, orally). plus Best Support Care ZD6474 (Vandetanib) 100 mg (one tablet per day, orally). plus Best Support Care Placebo plus Best Support Care Total of all reporting groups
Overall Number of Baseline Participants 19 25 23 67
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 19 participants 25 participants 23 participants 67 participants
56.6  (13.48) 61.2  (13.36) 57.3  (12.62) 58.37  (13.27)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 25 participants 23 participants 67 participants
Female
18
  94.7%
17
  68.0%
20
  87.0%
55
  82.1%
Male
1
   5.3%
8
  32.0%
3
  13.0%
12
  17.9%
Child-Pugh Score   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 19 participants 25 participants 23 participants 67 participants
Child-Pugh of 5 13 19 17 49
Child-Pugh of 6 6 6 6 18
[1]
Measure Description:

Child-Pugh Scale is used to assess the prognosis of chronic liver disease. The total score employs five clinical measures of liver disease: severity of ascites and of encephalopathy, abnormality in the serum bilirubin, serum albumin and clotting times. Each measure is scored 1-3, with 3 indicating most severe derangement.

The Total score ranges between 5 min to 15 max where lower score = less liver disease and higher score = chronic liver disease.

The number of patients with Child-PughTotal score of 5 and 6 is presented.

CLIP Score   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 19 participants 25 participants 23 participants 67 participants
CLIP 0 2 1 0 3
CLIP 1 5 5 3 13
CLIP 2 2 5 8 15
CLIP 3 4 8 6 18
CLIP 4 6 6 6 18
[1]
Measure Description:

Cancer of the Liver Italian Programme (CLIP) is used to evaluate both tumour extension and remnant liver function with a score of min 0 to max 4. The CLIP score consists of 4 variables: Child-Pugh stage, tumour morphology, alpa-fetoprotein (AFP), and portal vein thrombosis. The higher the CLIP score the worse the survival.

The number of patients with CLIP Total score of 0, 1, 2, 3 and 4 is presented.

1.Primary Outcome
Title Tumour Stabilisation Rate
Hide Description

Tumour stabilisation rate calculated as percentage of patients with best objective tumour response (Complete Response, Partial Response or Stable Disease) for >=16 weeks based on Response Evaluation Criteria in Solid Tumours (RECIST).

Complete Response - Disappearance of all target lesions; Partial Response - >=30% decrease in the sum of longest diameter of target lesions; Progressive Disease - >=20% increase in the sum of longest diameter of target lesions; Stable Disease - neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

Time Frame After 16 weeks of treatment.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis has been performed in the Intent-To-Treat (ITT) population.
Arm/Group Title ZD6474 300 ZD6474 100 Placebo
Hide Arm/Group Description:
ZD6474 (Vandetanib) 300 mg ( one tablet per day, orally). plus Best Support Care
ZD6474 (Vandetanib) 100 mg (one tablet per day, orally). plus Best Support Care
Placebo plus Best Support Care
Overall Number of Participants Analyzed 19 25 23
Measure Type: Number
Unit of Measure: percentage of patients
5.3 16.0 8.7
2.Secondary Outcome
Title Objective Response Rate
Hide Description

Objective Response rate defined as percentage of patients with Complete Response [CR] or Partial Response [PR] based on Response Evaluation Criteria in Solid Tumours (RECIST).

Partial response (PR) must have ≥ 30% decrease in the sum of longest diameter of all target lesions as assessed by Magnetic Resonance Imaging (MRI). Complete response (CR) must have disappearance of all target and non-target lesions as assessed by MRI.

Time Frame After 16 weeks of treatment.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis has been performed in the Intent-To-Treat (ITT) population.
Arm/Group Title ZD6474 300 ZD6474 100 Placebo
Hide Arm/Group Description:
ZD6474 (Vandetanib) 300 mg ( one tablet per day, orally). plus Best Support Care
ZD6474 (Vandetanib) 100 mg (one tablet per day, orally). plus Best Support Care
Placebo plus Best Support Care
Overall Number of Participants Analyzed 19 25 23
Measure Type: Number
Unit of Measure: percentage of patients
0 0 0
3.Secondary Outcome
Title Progression-free Survival
Hide Description Progression-free survival defined as the period from date of randomization(start of treatment) to date of disease progression or death.
Time Frame from the date of randomisation to the date of documented disease progression or death for any cause
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis has been performed in the Intent-To-Treat (ITT) population.
Arm/Group Title ZD6474 300 ZD6474 100 Placebo
Hide Arm/Group Description:
ZD6474 (Vandetanib) 300 mg ( one tablet per day, orally). plus Best Support Care
ZD6474 (Vandetanib) 100 mg (one tablet per day, orally). plus Best Support Care
Placebo plus Best Support Care
Overall Number of Participants Analyzed 19 25 23
Mean (95% Confidence Interval)
Unit of Measure: Days
32
(29 to 108)
53
(29 to 57)
29
(28 to 57)
4.Secondary Outcome
Title Overall Survival
Hide Description Overall survival defined as the time from randomization (start of treatment) until death from any cause.
Time Frame assessed up to 360 days
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis performed in the intent-To-Treat population.
Arm/Group Title ZD6474 300 ZD6474 100 Placebo
Hide Arm/Group Description:
ZD6474 (Vandetanib) 300 mg ( one tablet per day, orally). plus Best Support Care
ZD6474 (Vandetanib) 100 mg (one tablet per day, orally). plus Best Support Care
Placebo plus Best Support Care
Overall Number of Participants Analyzed 19 25 23
Median (95% Confidence Interval)
Unit of Measure: Days
181
(117 to 290)
175
(137 to 309)
130
(93 to 180)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title ZD6474 300 ZD6474 100 Placebo
Hide Arm/Group Description ZD6474 (Vandetanib) 300 mg ( one tablet per day, orally). plus Best Support Care ZD6474 (Vandetanib) 100 mg (one tablet per day, orally). plus Best Support Care Placebo plus Best Support Care
All-Cause Mortality
ZD6474 300 ZD6474 100 Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
ZD6474 300 ZD6474 100 Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/19 (31.58%)   4/25 (16.00%)   4/23 (17.39%) 
Cardiac disorders       
Myocardial Ischaemia  1  1/19 (5.26%)  0/25 (0.00%)  0/23 (0.00%) 
Gastrointestinal disorders       
Gastrointestinal Haemorrhage  1  2/19 (10.53%)  0/25 (0.00%)  0/23 (0.00%) 
Abdominal Pain  1  0/19 (0.00%)  1/25 (4.00%)  0/23 (0.00%) 
Oesophageal Varices Haemorrhage  1  0/19 (0.00%)  0/25 (0.00%)  1/23 (4.35%) 
Upper Gastrointestinal Haemorrhage  1  1/19 (5.26%)  0/25 (0.00%)  1/23 (4.35%) 
Vomiting  1  0/19 (0.00%)  1/25 (4.00%)  0/23 (0.00%) 
General disorders       
Mucosal Inflammation  1  0/19 (0.00%)  1/25 (4.00%)  0/23 (0.00%) 
Pyrexia  1  0/19 (0.00%)  1/25 (4.00%)  0/23 (0.00%) 
Hepatobiliary disorders       
Hepatic Failure  1  1/19 (5.26%)  0/25 (0.00%)  0/23 (0.00%) 
Infections and infestations       
Cellulitis  1  1/19 (5.26%)  0/25 (0.00%)  0/23 (0.00%) 
Pneumonia  1  0/19 (0.00%)  1/25 (4.00%)  0/23 (0.00%) 
Injury, poisoning and procedural complications       
Fracture  1  0/19 (0.00%)  0/25 (0.00%)  1/23 (4.35%) 
Weight Decreased  1  0/19 (0.00%)  0/25 (0.00%)  1/23 (4.35%) 
Psychiatric disorders       
Agitation  1  0/19 (0.00%)  1/25 (4.00%)  0/23 (0.00%) 
Renal and urinary disorders       
Renal Failure Acute  1  0/19 (0.00%)  0/25 (0.00%)  1/23 (4.35%) 
Skin and subcutaneous tissue disorders       
Stevens-Johnson Syndrome  1  1/19 (5.26%)  0/25 (0.00%)  0/23 (0.00%) 
Vascular disorders       
Hypertension  1  0/19 (0.00%)  1/25 (4.00%)  0/23 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
ZD6474 300 ZD6474 100 Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   18/19 (94.74%)   24/25 (96.00%)   21/23 (91.30%) 
Blood and lymphatic system disorders       
Anaemia  1  0/19 (0.00%)  0/25 (0.00%)  2/23 (8.70%) 
Deficiency Anaemia  1  1/19 (5.26%)  0/25 (0.00%)  0/23 (0.00%) 
Leukocytosis  1  1/19 (5.26%)  1/25 (4.00%)  1/23 (4.35%) 
Cardiac disorders       
Tachycardia  1  1/19 (5.26%)  0/25 (0.00%)  0/23 (0.00%) 
Ear and labyrinth disorders       
Tinnitus  1  1/19 (5.26%)  0/25 (0.00%)  0/23 (0.00%) 
Eye disorders       
Vision Blurred  1  1/19 (5.26%)  0/25 (0.00%)  0/23 (0.00%) 
Gastrointestinal disorders       
Diarrhoea  1  8/19 (42.11%)  9/25 (36.00%)  7/23 (30.43%) 
Constipation  1  2/19 (10.53%)  3/25 (12.00%)  5/23 (21.74%) 
Vomiting  1  2/19 (10.53%)  3/25 (12.00%)  5/23 (21.74%) 
Nausea  1  0/19 (0.00%)  3/25 (12.00%)  3/23 (13.04%) 
Abdominal Distension  1  2/19 (10.53%)  0/25 (0.00%)  0/23 (0.00%) 
Abdominal Pain Upper  1  1/19 (5.26%)  2/25 (8.00%)  2/23 (8.70%) 
Dyspepsia  1  0/19 (0.00%)  2/25 (8.00%)  2/23 (8.70%) 
Gastric Ulcer  1  2/19 (10.53%)  0/25 (0.00%)  0/23 (0.00%) 
Mouth Ulceration  1  2/19 (10.53%)  0/25 (0.00%)  0/23 (0.00%) 
Periodontitis  1  0/19 (0.00%)  2/25 (8.00%)  0/23 (0.00%) 
Anal Fissure  1  1/19 (5.26%)  0/25 (0.00%)  0/23 (0.00%) 
Dry Mouth  1  1/19 (5.26%)  1/25 (4.00%)  0/23 (0.00%) 
Duodenitis  1  1/19 (5.26%)  0/25 (0.00%)  0/23 (0.00%) 
Frequent Bowel Movements  1  1/19 (5.26%)  0/25 (0.00%)  0/23 (0.00%) 
Gastrointestinal Disorder  1  1/19 (5.26%)  0/25 (0.00%)  0/23 (0.00%) 
Haemorrhoidal Haemorrhage  1  2/19 (10.53%)  0/25 (0.00%)  0/23 (0.00%) 
Haemorrhoids  1  1/19 (5.26%)  0/25 (0.00%)  0/23 (0.00%) 
Irritable Bowel Syndrome  1  1/19 (5.26%)  0/25 (0.00%)  1/23 (4.35%) 
Lip Ulceration  1  1/19 (5.26%)  0/25 (0.00%)  0/23 (0.00%) 
Oral Pain  1  1/19 (5.26%)  0/25 (0.00%)  0/23 (0.00%) 
Peptic Ulcer  1  1/19 (5.26%)  0/25 (0.00%)  0/23 (0.00%) 
Rectal Tenesmus  1  1/19 (5.26%)  0/25 (0.00%)  1/23 (4.35%) 
Stomatitis  1  1/19 (5.26%)  1/25 (4.00%)  0/23 (0.00%) 
General disorders       
Fatigue  1  1/19 (5.26%)  3/25 (12.00%)  1/23 (4.35%) 
Oedema Peripheral  1  1/19 (5.26%)  1/25 (4.00%)  3/23 (13.04%) 
Pyrexia  1  2/19 (10.53%)  4/25 (16.00%)  3/23 (13.04%) 
Mucosal Inflammation  1  1/19 (5.26%)  3/25 (12.00%)  0/23 (0.00%) 
Malaise  1  1/19 (5.26%)  1/25 (4.00%)  1/23 (4.35%) 
Infections and infestations       
Upper Respiratory Tract Infection  1  1/19 (5.26%)  4/25 (16.00%)  2/23 (8.70%) 
Bronchitis  1  1/19 (5.26%)  2/25 (8.00%)  0/23 (0.00%) 
Folliculitis  1  1/19 (5.26%)  0/25 (0.00%)  0/23 (0.00%) 
Injury, poisoning and procedural complications       
Post Procedural Complication  1  0/19 (0.00%)  0/25 (0.00%)  2/23 (8.70%) 
Limb Injury  1  1/19 (5.26%)  1/25 (4.00%)  0/23 (0.00%) 
Wound  1  1/19 (5.26%)  0/25 (0.00%)  1/23 (4.35%) 
Electrocardiogram Qt Prolonged  1  2/19 (10.53%)  2/25 (8.00%)  1/23 (4.35%) 
Weight Decreased  1  1/19 (5.26%)  1/25 (4.00%)  3/23 (13.04%) 
Aspartate Aminotransferase Increased  1  1/19 (5.26%)  0/25 (0.00%)  0/23 (0.00%) 
Metabolism and nutrition disorders       
Decreased Appetite  1  4/19 (21.05%)  3/25 (12.00%)  6/23 (26.09%) 
Hyperkalaemia  1  2/19 (10.53%)  0/25 (0.00%)  1/23 (4.35%) 
Hypoglycaemia  1  0/19 (0.00%)  2/25 (8.00%)  0/23 (0.00%) 
Hypomagnesaemia  1  0/19 (0.00%)  2/25 (8.00%)  0/23 (0.00%) 
Hyperglycaemia  1  1/19 (5.26%)  0/25 (0.00%)  0/23 (0.00%) 
Hyponatraemia  1  1/19 (5.26%)  0/25 (0.00%)  1/23 (4.35%) 
Musculoskeletal and connective tissue disorders       
Back Pain  1  0/19 (0.00%)  1/25 (4.00%)  2/23 (8.70%) 
Musculoskeletal Pain  1  1/19 (5.26%)  2/25 (8.00%)  0/23 (0.00%) 
Neck Pain  1  1/19 (5.26%)  0/25 (0.00%)  0/23 (0.00%) 
Osteoarthritis  1  1/19 (5.26%)  0/25 (0.00%)  0/23 (0.00%) 
Nervous system disorders       
Dizziness  1  2/19 (10.53%)  1/25 (4.00%)  5/23 (21.74%) 
Headache  1  1/19 (5.26%)  0/25 (0.00%)  0/23 (0.00%) 
Poor Quality Sleep  1  1/19 (5.26%)  0/25 (0.00%)  0/23 (0.00%) 
Psychiatric disorders       
Insomnia  1  3/19 (15.79%)  4/25 (16.00%)  5/23 (21.74%) 
Anxiety  1  1/19 (5.26%)  0/25 (0.00%)  2/23 (8.70%) 
Renal and urinary disorders       
Nocturia  1  0/19 (0.00%)  0/25 (0.00%)  3/23 (13.04%) 
Dysuria  1  1/19 (5.26%)  1/25 (4.00%)  1/23 (4.35%) 
Proteinuria  1  1/19 (5.26%)  0/25 (0.00%)  0/23 (0.00%) 
Reproductive system and breast disorders       
Scrotal Ulcer  1  1/19 (5.26%)  0/25 (0.00%)  0/23 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  1/19 (5.26%)  4/25 (16.00%)  3/23 (13.04%) 
Nasal Congestion  1  0/19 (0.00%)  0/25 (0.00%)  2/23 (8.70%) 
Rhinorrhoea  1  1/19 (5.26%)  0/25 (0.00%)  2/23 (8.70%) 
Dyspnoea  1  1/19 (5.26%)  1/25 (4.00%)  0/23 (0.00%) 
Hiccups  1  1/19 (5.26%)  0/25 (0.00%)  1/23 (4.35%) 
Skin and subcutaneous tissue disorders       
Rash  1  9/19 (47.37%)  6/25 (24.00%)  6/23 (26.09%) 
Pruritus  1  3/19 (15.79%)  5/25 (20.00%)  2/23 (8.70%) 
Acne  1  4/19 (21.05%)  4/25 (16.00%)  4/23 (17.39%) 
Photosensitivity Reaction  1  1/19 (5.26%)  3/25 (12.00%)  0/23 (0.00%) 
Rash Pruritic  1  0/19 (0.00%)  2/25 (8.00%)  0/23 (0.00%) 
Dermatitis Contact  1  1/19 (5.26%)  0/25 (0.00%)  0/23 (0.00%) 
Dry Skin  1  1/19 (5.26%)  0/25 (0.00%)  0/23 (0.00%) 
Erythema  1  1/19 (5.26%)  1/25 (4.00%)  0/23 (0.00%) 
Rash Erythematous  1  1/19 (5.26%)  0/25 (0.00%)  0/23 (0.00%) 
Rash Macular  1  1/19 (5.26%)  0/25 (0.00%)  0/23 (0.00%) 
Skin Plaque  1  1/19 (5.26%)  0/25 (0.00%)  0/23 (0.00%) 
Vascular disorders       
Hypertension  1  2/19 (10.53%)  5/25 (20.00%)  1/23 (4.35%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.1
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
Name/Title: Trial Transparency Team
Organization: Sanofi
Responsible Party: Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT00508001     History of Changes
Other Study ID Numbers: D4200C00072
First Submitted: July 25, 2007
First Posted: July 27, 2007
Results First Submitted: May 9, 2011
Results First Posted: July 17, 2012
Last Update Posted: October 10, 2016