Trial Outcomes & Findings for Phase II Study of Best Support Care (BSC) Plus ZD6474(Vandetanib) in Patients With Inoperable Hepatocellular Carcinoma (HCC) (NCT NCT00508001)
NCT ID: NCT00508001
Last Updated: 2016-10-10
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
67 participants
Primary outcome timeframe
After 16 weeks of treatment.
Results posted on
2016-10-10
Participant Flow
78 patients were recruited at medical clinic
11 patients were screening failure due to inclusion criteria or exclusion criteria is not fulfilled
Participant milestones
| Measure |
ZD6474 300
ZD6474 (Vandetanib) 300 mg ( one tablet per day, orally). plus Best Support Care
|
ZD6474 100
ZD6474 (Vandetanib) 100 mg (one tablet per day, orally). plus Best Support Care
|
Placebo
Placebo plus Best Support Care
|
|---|---|---|---|
|
Overall Study
STARTED
|
19
|
25
|
23
|
|
Overall Study
Secondary Treatment Phase
|
0
|
13
|
16
|
|
Overall Study
COMPLETED
|
0
|
13
|
16
|
|
Overall Study
NOT COMPLETED
|
19
|
12
|
7
|
Reasons for withdrawal
| Measure |
ZD6474 300
ZD6474 (Vandetanib) 300 mg ( one tablet per day, orally). plus Best Support Care
|
ZD6474 100
ZD6474 (Vandetanib) 100 mg (one tablet per day, orally). plus Best Support Care
|
Placebo
Placebo plus Best Support Care
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
2
|
0
|
4
|
|
Overall Study
condition under investigation worsened
|
13
|
7
|
1
|
|
Overall Study
Death
|
0
|
1
|
1
|
|
Overall Study
Withdrawal by Subject
|
4
|
4
|
1
|
Baseline Characteristics
Phase II Study of Best Support Care (BSC) Plus ZD6474(Vandetanib) in Patients With Inoperable Hepatocellular Carcinoma (HCC)
Baseline characteristics by cohort
| Measure |
ZD6474 300
n=19 Participants
ZD6474 (Vandetanib) 300 mg ( one tablet per day, orally). plus Best Support Care
|
ZD6474 100
n=25 Participants
ZD6474 (Vandetanib) 100 mg (one tablet per day, orally). plus Best Support Care
|
Placebo
n=23 Participants
Placebo plus Best Support Care
|
Total
n=67 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
56.6 years
STANDARD_DEVIATION 13.48 • n=5 Participants
|
61.2 years
STANDARD_DEVIATION 13.36 • n=7 Participants
|
57.3 years
STANDARD_DEVIATION 12.62 • n=5 Participants
|
58.37 years
STANDARD_DEVIATION 13.27 • n=4 Participants
|
|
Sex: Female, Male
Female
|
18 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
55 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
12 Participants
n=4 Participants
|
|
Child-Pugh Score
Child-Pugh of 5
|
13 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
49 Participants
n=4 Participants
|
|
Child-Pugh Score
Child-Pugh of 6
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
18 Participants
n=4 Participants
|
|
CLIP Score
CLIP 0
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
CLIP Score
CLIP 1
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
13 Participants
n=4 Participants
|
|
CLIP Score
CLIP 2
|
2 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
15 Participants
n=4 Participants
|
|
CLIP Score
CLIP 3
|
4 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
18 Participants
n=4 Participants
|
|
CLIP Score
CLIP 4
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
18 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: After 16 weeks of treatment.Population: The analysis has been performed in the Intent-To-Treat (ITT) population.
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.
Outcome measures
| Measure |
ZD6474 300
n=19 Participants
ZD6474 (Vandetanib) 300 mg ( one tablet per day, orally). plus Best Support Care
|
ZD6474 100
n=25 Participants
ZD6474 (Vandetanib) 100 mg (one tablet per day, orally). plus Best Support Care
|
Placebo
n=23 Participants
Placebo plus Best Support Care
|
|---|---|---|---|
|
Tumour Stabilisation Rate
|
5.3 percentage of patients
|
16.0 percentage of patients
|
8.7 percentage of patients
|
SECONDARY outcome
Timeframe: After 16 weeks of treatment.Population: The analysis has been performed in the Intent-To-Treat (ITT) population.
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.
Outcome measures
| Measure |
ZD6474 300
n=19 Participants
ZD6474 (Vandetanib) 300 mg ( one tablet per day, orally). plus Best Support Care
|
ZD6474 100
n=25 Participants
ZD6474 (Vandetanib) 100 mg (one tablet per day, orally). plus Best Support Care
|
Placebo
n=23 Participants
Placebo plus Best Support Care
|
|---|---|---|---|
|
Objective Response Rate
|
0 percentage of patients
|
0 percentage of patients
|
0 percentage of patients
|
SECONDARY outcome
Timeframe: from the date of randomisation to the date of documented disease progression or death for any causePopulation: The analysis has been performed in the Intent-To-Treat (ITT) population.
Progression-free survival defined as the period from date of randomization(start of treatment) to date of disease progression or death.
Outcome measures
| Measure |
ZD6474 300
n=19 Participants
ZD6474 (Vandetanib) 300 mg ( one tablet per day, orally). plus Best Support Care
|
ZD6474 100
n=25 Participants
ZD6474 (Vandetanib) 100 mg (one tablet per day, orally). plus Best Support Care
|
Placebo
n=23 Participants
Placebo plus Best Support Care
|
|---|---|---|---|
|
Progression-free Survival
|
32 Days
95% Confidence Interval 29 • Interval 29.0 to 108.0
|
53 Days
95% Confidence Interval 29 • Interval 29.0 to 57.0
|
29 Days
95% Confidence Interval 28 • Interval 28.0 to 57.0
|
SECONDARY outcome
Timeframe: assessed up to 360 daysPopulation: The analysis performed in the intent-To-Treat population.
Overall survival defined as the time from randomization (start of treatment) until death from any cause.
Outcome measures
| Measure |
ZD6474 300
n=19 Participants
ZD6474 (Vandetanib) 300 mg ( one tablet per day, orally). plus Best Support Care
|
ZD6474 100
n=25 Participants
ZD6474 (Vandetanib) 100 mg (one tablet per day, orally). plus Best Support Care
|
Placebo
n=23 Participants
Placebo plus Best Support Care
|
|---|---|---|---|
|
Overall Survival
|
181 Days
Interval 117.0 to 290.0
|
175 Days
Interval 137.0 to 309.0
|
130 Days
Interval 93.0 to 180.0
|
Adverse Events
ZD6474 300
Serious events: 6 serious events
Other events: 18 other events
Deaths: 0 deaths
ZD6474 100
Serious events: 4 serious events
Other events: 24 other events
Deaths: 0 deaths
Placebo
Serious events: 4 serious events
Other events: 21 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
ZD6474 300
n=19 participants at risk
ZD6474 (Vandetanib) 300 mg ( one tablet per day, orally). plus Best Support Care
|
ZD6474 100
n=25 participants at risk
ZD6474 (Vandetanib) 100 mg (one tablet per day, orally). plus Best Support Care
|
Placebo
n=23 participants at risk
Placebo plus Best Support Care
|
|---|---|---|---|
|
Cardiac disorders
Myocardial Ischaemia
|
5.3%
1/19
|
0.00%
0/25
|
0.00%
0/23
|
|
Gastrointestinal disorders
Gastrointestinal Haemorrhage
|
10.5%
2/19
|
0.00%
0/25
|
0.00%
0/23
|
|
Gastrointestinal disorders
Abdominal Pain
|
0.00%
0/19
|
4.0%
1/25
|
0.00%
0/23
|
|
Gastrointestinal disorders
Oesophageal Varices Haemorrhage
|
0.00%
0/19
|
0.00%
0/25
|
4.3%
1/23
|
|
Gastrointestinal disorders
Upper Gastrointestinal Haemorrhage
|
5.3%
1/19
|
0.00%
0/25
|
4.3%
1/23
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/19
|
4.0%
1/25
|
0.00%
0/23
|
|
General disorders
Mucosal Inflammation
|
0.00%
0/19
|
4.0%
1/25
|
0.00%
0/23
|
|
General disorders
Pyrexia
|
0.00%
0/19
|
4.0%
1/25
|
0.00%
0/23
|
|
Hepatobiliary disorders
Hepatic Failure
|
5.3%
1/19
|
0.00%
0/25
|
0.00%
0/23
|
|
Infections and infestations
Cellulitis
|
5.3%
1/19
|
0.00%
0/25
|
0.00%
0/23
|
|
Infections and infestations
Pneumonia
|
0.00%
0/19
|
4.0%
1/25
|
0.00%
0/23
|
|
Injury, poisoning and procedural complications
Fracture
|
0.00%
0/19
|
0.00%
0/25
|
4.3%
1/23
|
|
Injury, poisoning and procedural complications
Weight Decreased
|
0.00%
0/19
|
0.00%
0/25
|
4.3%
1/23
|
|
Psychiatric disorders
Agitation
|
0.00%
0/19
|
4.0%
1/25
|
0.00%
0/23
|
|
Renal and urinary disorders
Renal Failure Acute
|
0.00%
0/19
|
0.00%
0/25
|
4.3%
1/23
|
|
Skin and subcutaneous tissue disorders
Stevens-Johnson Syndrome
|
5.3%
1/19
|
0.00%
0/25
|
0.00%
0/23
|
|
Vascular disorders
Hypertension
|
0.00%
0/19
|
4.0%
1/25
|
0.00%
0/23
|
Other adverse events
| Measure |
ZD6474 300
n=19 participants at risk
ZD6474 (Vandetanib) 300 mg ( one tablet per day, orally). plus Best Support Care
|
ZD6474 100
n=25 participants at risk
ZD6474 (Vandetanib) 100 mg (one tablet per day, orally). plus Best Support Care
|
Placebo
n=23 participants at risk
Placebo plus Best Support Care
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/19
|
0.00%
0/25
|
8.7%
2/23
|
|
Blood and lymphatic system disorders
Deficiency Anaemia
|
5.3%
1/19
|
0.00%
0/25
|
0.00%
0/23
|
|
Blood and lymphatic system disorders
Leukocytosis
|
5.3%
1/19
|
4.0%
1/25
|
4.3%
1/23
|
|
Cardiac disorders
Tachycardia
|
5.3%
1/19
|
0.00%
0/25
|
0.00%
0/23
|
|
Ear and labyrinth disorders
Tinnitus
|
5.3%
1/19
|
0.00%
0/25
|
0.00%
0/23
|
|
Eye disorders
Vision Blurred
|
5.3%
1/19
|
0.00%
0/25
|
0.00%
0/23
|
|
Gastrointestinal disorders
Diarrhoea
|
42.1%
8/19
|
36.0%
9/25
|
30.4%
7/23
|
|
Gastrointestinal disorders
Constipation
|
10.5%
2/19
|
12.0%
3/25
|
21.7%
5/23
|
|
Gastrointestinal disorders
Vomiting
|
10.5%
2/19
|
12.0%
3/25
|
21.7%
5/23
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/19
|
12.0%
3/25
|
13.0%
3/23
|
|
Gastrointestinal disorders
Abdominal Distension
|
10.5%
2/19
|
0.00%
0/25
|
0.00%
0/23
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
5.3%
1/19
|
8.0%
2/25
|
8.7%
2/23
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/19
|
8.0%
2/25
|
8.7%
2/23
|
|
Gastrointestinal disorders
Gastric Ulcer
|
10.5%
2/19
|
0.00%
0/25
|
0.00%
0/23
|
|
Gastrointestinal disorders
Mouth Ulceration
|
10.5%
2/19
|
0.00%
0/25
|
0.00%
0/23
|
|
Gastrointestinal disorders
Periodontitis
|
0.00%
0/19
|
8.0%
2/25
|
0.00%
0/23
|
|
Gastrointestinal disorders
Anal Fissure
|
5.3%
1/19
|
0.00%
0/25
|
0.00%
0/23
|
|
Gastrointestinal disorders
Dry Mouth
|
5.3%
1/19
|
4.0%
1/25
|
0.00%
0/23
|
|
Gastrointestinal disorders
Duodenitis
|
5.3%
1/19
|
0.00%
0/25
|
0.00%
0/23
|
|
Gastrointestinal disorders
Frequent Bowel Movements
|
5.3%
1/19
|
0.00%
0/25
|
0.00%
0/23
|
|
Gastrointestinal disorders
Gastrointestinal Disorder
|
5.3%
1/19
|
0.00%
0/25
|
0.00%
0/23
|
|
Gastrointestinal disorders
Haemorrhoidal Haemorrhage
|
10.5%
2/19
|
0.00%
0/25
|
0.00%
0/23
|
|
Gastrointestinal disorders
Haemorrhoids
|
5.3%
1/19
|
0.00%
0/25
|
0.00%
0/23
|
|
Gastrointestinal disorders
Irritable Bowel Syndrome
|
5.3%
1/19
|
0.00%
0/25
|
4.3%
1/23
|
|
Gastrointestinal disorders
Lip Ulceration
|
5.3%
1/19
|
0.00%
0/25
|
0.00%
0/23
|
|
Gastrointestinal disorders
Oral Pain
|
5.3%
1/19
|
0.00%
0/25
|
0.00%
0/23
|
|
Gastrointestinal disorders
Peptic Ulcer
|
5.3%
1/19
|
0.00%
0/25
|
0.00%
0/23
|
|
Gastrointestinal disorders
Rectal Tenesmus
|
5.3%
1/19
|
0.00%
0/25
|
4.3%
1/23
|
|
Gastrointestinal disorders
Stomatitis
|
5.3%
1/19
|
4.0%
1/25
|
0.00%
0/23
|
|
General disorders
Fatigue
|
5.3%
1/19
|
12.0%
3/25
|
4.3%
1/23
|
|
General disorders
Oedema Peripheral
|
5.3%
1/19
|
4.0%
1/25
|
13.0%
3/23
|
|
General disorders
Pyrexia
|
10.5%
2/19
|
16.0%
4/25
|
13.0%
3/23
|
|
General disorders
Mucosal Inflammation
|
5.3%
1/19
|
12.0%
3/25
|
0.00%
0/23
|
|
General disorders
Malaise
|
5.3%
1/19
|
4.0%
1/25
|
4.3%
1/23
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
5.3%
1/19
|
16.0%
4/25
|
8.7%
2/23
|
|
Infections and infestations
Bronchitis
|
5.3%
1/19
|
8.0%
2/25
|
0.00%
0/23
|
|
Infections and infestations
Folliculitis
|
5.3%
1/19
|
0.00%
0/25
|
0.00%
0/23
|
|
Injury, poisoning and procedural complications
Post Procedural Complication
|
0.00%
0/19
|
0.00%
0/25
|
8.7%
2/23
|
|
Injury, poisoning and procedural complications
Limb Injury
|
5.3%
1/19
|
4.0%
1/25
|
0.00%
0/23
|
|
Injury, poisoning and procedural complications
Wound
|
5.3%
1/19
|
0.00%
0/25
|
4.3%
1/23
|
|
Injury, poisoning and procedural complications
Electrocardiogram Qt Prolonged
|
10.5%
2/19
|
8.0%
2/25
|
4.3%
1/23
|
|
Injury, poisoning and procedural complications
Weight Decreased
|
5.3%
1/19
|
4.0%
1/25
|
13.0%
3/23
|
|
Injury, poisoning and procedural complications
Aspartate Aminotransferase Increased
|
5.3%
1/19
|
0.00%
0/25
|
0.00%
0/23
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
21.1%
4/19
|
12.0%
3/25
|
26.1%
6/23
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
10.5%
2/19
|
0.00%
0/25
|
4.3%
1/23
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/19
|
8.0%
2/25
|
0.00%
0/23
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
0.00%
0/19
|
8.0%
2/25
|
0.00%
0/23
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
5.3%
1/19
|
0.00%
0/25
|
0.00%
0/23
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
5.3%
1/19
|
0.00%
0/25
|
4.3%
1/23
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
0.00%
0/19
|
4.0%
1/25
|
8.7%
2/23
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain
|
5.3%
1/19
|
8.0%
2/25
|
0.00%
0/23
|
|
Musculoskeletal and connective tissue disorders
Neck Pain
|
5.3%
1/19
|
0.00%
0/25
|
0.00%
0/23
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
5.3%
1/19
|
0.00%
0/25
|
0.00%
0/23
|
|
Nervous system disorders
Dizziness
|
10.5%
2/19
|
4.0%
1/25
|
21.7%
5/23
|
|
Nervous system disorders
Headache
|
5.3%
1/19
|
0.00%
0/25
|
0.00%
0/23
|
|
Nervous system disorders
Poor Quality Sleep
|
5.3%
1/19
|
0.00%
0/25
|
0.00%
0/23
|
|
Psychiatric disorders
Insomnia
|
15.8%
3/19
|
16.0%
4/25
|
21.7%
5/23
|
|
Psychiatric disorders
Anxiety
|
5.3%
1/19
|
0.00%
0/25
|
8.7%
2/23
|
|
Renal and urinary disorders
Nocturia
|
0.00%
0/19
|
0.00%
0/25
|
13.0%
3/23
|
|
Renal and urinary disorders
Dysuria
|
5.3%
1/19
|
4.0%
1/25
|
4.3%
1/23
|
|
Renal and urinary disorders
Proteinuria
|
5.3%
1/19
|
0.00%
0/25
|
0.00%
0/23
|
|
Reproductive system and breast disorders
Scrotal Ulcer
|
5.3%
1/19
|
0.00%
0/25
|
0.00%
0/23
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.3%
1/19
|
16.0%
4/25
|
13.0%
3/23
|
|
Respiratory, thoracic and mediastinal disorders
Nasal Congestion
|
0.00%
0/19
|
0.00%
0/25
|
8.7%
2/23
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
5.3%
1/19
|
0.00%
0/25
|
8.7%
2/23
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
5.3%
1/19
|
4.0%
1/25
|
0.00%
0/23
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
5.3%
1/19
|
0.00%
0/25
|
4.3%
1/23
|
|
Skin and subcutaneous tissue disorders
Rash
|
47.4%
9/19
|
24.0%
6/25
|
26.1%
6/23
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
15.8%
3/19
|
20.0%
5/25
|
8.7%
2/23
|
|
Skin and subcutaneous tissue disorders
Acne
|
21.1%
4/19
|
16.0%
4/25
|
17.4%
4/23
|
|
Skin and subcutaneous tissue disorders
Photosensitivity Reaction
|
5.3%
1/19
|
12.0%
3/25
|
0.00%
0/23
|
|
Skin and subcutaneous tissue disorders
Rash Pruritic
|
0.00%
0/19
|
8.0%
2/25
|
0.00%
0/23
|
|
Skin and subcutaneous tissue disorders
Dermatitis Contact
|
5.3%
1/19
|
0.00%
0/25
|
0.00%
0/23
|
|
Skin and subcutaneous tissue disorders
Dry Skin
|
5.3%
1/19
|
0.00%
0/25
|
0.00%
0/23
|
|
Skin and subcutaneous tissue disorders
Erythema
|
5.3%
1/19
|
4.0%
1/25
|
0.00%
0/23
|
|
Skin and subcutaneous tissue disorders
Rash Erythematous
|
5.3%
1/19
|
0.00%
0/25
|
0.00%
0/23
|
|
Skin and subcutaneous tissue disorders
Rash Macular
|
5.3%
1/19
|
0.00%
0/25
|
0.00%
0/23
|
|
Skin and subcutaneous tissue disorders
Skin Plaque
|
5.3%
1/19
|
0.00%
0/25
|
0.00%
0/23
|
|
Vascular disorders
Hypertension
|
10.5%
2/19
|
20.0%
5/25
|
4.3%
1/23
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER