Trial Outcomes & Findings for A Study To Assess ZD6474 (ZACTIMA™) Monotherapy In Locally Advanced or Metastatic Hereditary Medullary Thyroid Cancer (NCT NCT00358956)

NCT ID: NCT00358956

Last Updated: 2017-01-30

Results Overview

The ORR is the number of patients that are responders ie those patients with a confirmed best objective response of complete response (CR) or partial response (PR) as defined by RECIST criteria. The categories for best objective response are CR, PR, stable disease (SD)\>= 12 weeks, progressive disease (PD) or NE.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

19 participants

Primary outcome timeframe

RECIST assessed at screening (up to 3 weeks prior to first dose), then every 12 weeks (± 2 weeks), from date of first dose to objective progression, up to and including discontinuation of study treatment.

Results posted on

2017-01-30

Participant Flow

From 29 August 2006 to 31 January 2008, 19 participants in 9 centers in 8 global countries received 100 mg vandetanib.

22 participants were screened; 19 participants received treatment.

Participant milestones

Participant milestones
Measure
ZD6474 (ZACTIMA™) 100 mg
ZD6474 (ZACTIMA™)100 mg daily
Overall Study
STARTED
19
Overall Study
COMPLETED
11
Overall Study
NOT COMPLETED
8

Reasons for withdrawal

Reasons for withdrawal
Measure
ZD6474 (ZACTIMA™) 100 mg
ZD6474 (ZACTIMA™)100 mg daily
Overall Study
Adverse Event
3
Overall Study
condition under investigation worsened
4
Overall Study
Withdrawal by Subject
1

Baseline Characteristics

A Study To Assess ZD6474 (ZACTIMA™) Monotherapy In Locally Advanced or Metastatic Hereditary Medullary Thyroid Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
ZD6474 (ZACTIMA™) 100 mg
n=19 Participants
ZD6474 (ZACTIMA™)100 mg daily
Age, Continuous
44.7 years
n=5 Participants
Gender
Female
6 Participants
n=5 Participants
Gender
Male
13 Participants
n=5 Participants

PRIMARY outcome

Timeframe: RECIST assessed at screening (up to 3 weeks prior to first dose), then every 12 weeks (± 2 weeks), from date of first dose to objective progression, up to and including discontinuation of study treatment.

The ORR is the number of patients that are responders ie those patients with a confirmed best objective response of complete response (CR) or partial response (PR) as defined by RECIST criteria. The categories for best objective response are CR, PR, stable disease (SD)\>= 12 weeks, progressive disease (PD) or NE.

Outcome measures

Outcome measures
Measure
ZD6474 (ZACTIMA™) 100 mg
n=19 Participants
ZD6474 (ZACTIMA™)100 mg daily
Objective Response Rate (ORR)
3 Participants

SECONDARY outcome

Timeframe: RECIST assessed at screening (up to 3 weeks prior to first dose), then every 12 weeks (± 2 weeks), from date of first dose to objective progression, up to and including discontinuation of study treatment.

Median progression free survival (months) estimated from a Weibull model with corresponding 95% confidence intervals. Progression free survival is the time from randomisation until objective disease progression (determined by RECIST assessments) or death (by any cause in the absence of objective progression) provided death is within 3 months from the last evaluable RECIST assessment.

Outcome measures

Outcome measures
Measure
ZD6474 (ZACTIMA™) 100 mg
n=19 Participants
ZD6474 (ZACTIMA™)100 mg daily
Progression-Free Survival (PFS)
16.2 Months
Interval 6.8 to 38.6

SECONDARY outcome

Timeframe: RECIST assessed at screening (up to 3 weeks prior to first dose), then every 12 weeks (± 2 weeks), from date of first dose to objective progression, up to and including discontinuation of study treatment.

Disease control rate is defined as the number of patients who achieved disease control at 8 weeks following randomisation. Disease control at 8 weeks is defined as a best objective response of complete response (CR), partial response (PR) or stable disease (SD) \>= 24 weeks

Outcome measures

Outcome measures
Measure
ZD6474 (ZACTIMA™) 100 mg
n=19 Participants
ZD6474 (ZACTIMA™)100 mg daily
Disease Control Rate (DCR)
13 Participants

SECONDARY outcome

Timeframe: WHO PS assessed at screening (up to 3 weeks prior to first dose), baseline and then every 12 weeks (± 2 weeks), up to and including discontinuation of study treatment.

Number of patients demonstrating an improvement from baseline to 24 weeks in WHO PS. Where WHO PS is the standard scale with patients scored (0 healthy - 5 dead) based on their physical capabilities

Outcome measures

Outcome measures
Measure
ZD6474 (ZACTIMA™) 100 mg
n=19 Participants
ZD6474 (ZACTIMA™)100 mg daily
World Heath Organization (WHO) Performance Status
0 Participants

SECONDARY outcome

Timeframe: Symptomatic diarrhea was assessed using stool frequency diaries. Baseline was established using the average of the 4 days immediately prior to first dose, then weekly until discontinuation of study treatment.

Symptomatic response will be defined as at least a 50% decrease in the stool frequency (represented by a persistent decrease in stool frequency over 4 weeks), taking as reference the baseline (mean) level.

Outcome measures

Outcome measures
Measure
ZD6474 (ZACTIMA™) 100 mg
n=19 Participants
ZD6474 (ZACTIMA™)100 mg daily
Symptomatic Response
0 Participants

SECONDARY outcome

Timeframe: Blood samples for analysis of CTN were taken at screening (0, 1, 4, and 8 hours to determine the baseline CTN/CEA level) then every 4 weeks until discontinuation Time point(s) at which outcome measure was assessed. (Limit: 255 characters)

A patient's best biochemical response was calculated from assessments performed at baseline and during treatment. Responders were those patients with a best biochemical response of CR or PR, confirmed by repeat assessments, which were to be performed no less than 4 weeks after the criteria for PR or CR were first met.

Outcome measures

Outcome measures
Measure
ZD6474 (ZACTIMA™) 100 mg
n=19 Participants
ZD6474 (ZACTIMA™)100 mg daily
Biochemical Response Calcitonin (CTN )
3 Participants

SECONDARY outcome

Timeframe: Blood samples for analysis of CTN were taken at screening (0, 1, 4, and 8 hours to determine the baseline CTN/CEA level) then every 4 weeks until discontinuation

A patient's best biochemical response was calculated from assessments performed at baseline and during treatment. Responders were those patients with a best biochemical response of CR or PR, confirmed by repeat assessments, which were to be performed no less than 4 weeks after the criteria for Partial Response (PR) or Complete Response (CR) were first met.

Outcome measures

Outcome measures
Measure
ZD6474 (ZACTIMA™) 100 mg
n=19 Participants
ZD6474 (ZACTIMA™)100 mg daily
Biochemical Response Carcinoembryonic Antigen CEA)
1 Participants

Adverse Events

ZD6474 (ZACTIMA™) 100 mg

Serious events: 4 serious events
Other events: 18 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
ZD6474 (ZACTIMA™) 100 mg
n=19 participants at risk
ZD6474 (ZACTIMA™)100 mg daily
Endocrine disorders
Diabetes Insipidus
5.3%
1/19
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Phaeochromocytoma
10.5%
2/19
Respiratory, thoracic and mediastinal disorders
Pneumonia Aspiration
5.3%
1/19

Other adverse events

Other adverse events
Measure
ZD6474 (ZACTIMA™) 100 mg
n=19 participants at risk
ZD6474 (ZACTIMA™)100 mg daily
Infections and infestations
Bronchitis
5.3%
1/19
Infections and infestations
Furuncle
5.3%
1/19
Infections and infestations
Paronychia
5.3%
1/19
Ear and labyrinth disorders
Deafness Unilateral
5.3%
1/19
Endocrine disorders
Hypothyroidism
10.5%
2/19
Eye disorders
Conjunctivitis
5.3%
1/19
Eye disorders
Diplopia
5.3%
1/19
Eye disorders
Visual Disturbance
5.3%
1/19
Gastrointestinal disorders
Diarrhoea
47.4%
9/19
Gastrointestinal disorders
Constipation
21.1%
4/19
Gastrointestinal disorders
Nausea
15.8%
3/19
Gastrointestinal disorders
Abdominal Pain
10.5%
2/19
Gastrointestinal disorders
Dyspepsia
10.5%
2/19
Gastrointestinal disorders
Flatulence
10.5%
2/19
Gastrointestinal disorders
Dry Mouth
5.3%
1/19
Gastrointestinal disorders
Haemorrhoidal Haemorrhage
5.3%
1/19
Gastrointestinal disorders
Haemorrhoids
5.3%
1/19
Gastrointestinal disorders
Oral Discomfort
5.3%
1/19
Gastrointestinal disorders
Vomiting
5.3%
1/19
General disorders
Fatigue
47.4%
9/19
General disorders
Asthenia
10.5%
2/19
General disorders
Influenza Like Illness
5.3%
1/19
General disorders
Malaise
5.3%
1/19
General disorders
Mucous Membrane Disorder
5.3%
1/19
General disorders
Thirst
5.3%
1/19
Infections and infestations
Folliculitis
10.5%
2/19
Infections and infestations
Nasopharyngitis
10.5%
2/19
Infections and infestations
Pharyngitis
5.3%
1/19
Infections and infestations
Tinea Pedis
5.3%
1/19
Infections and infestations
Upper Respiratory Tract Infection
5.3%
1/19
Infections and infestations
Weight Decreased
10.5%
2/19
Infections and infestations
Electrocardiogram Qt Prolonged
5.3%
1/19
Infections and infestations
Weight Increased
5.3%
1/19
Metabolism and nutrition disorders
Anorexia
21.1%
4/19
Metabolism and nutrition disorders
Hypocalcaemia
5.3%
1/19
Musculoskeletal and connective tissue disorders
Back Pain
15.8%
3/19
Musculoskeletal and connective tissue disorders
Arthralgia
10.5%
2/19
Musculoskeletal and connective tissue disorders
Mobility Decreased
5.3%
1/19
Musculoskeletal and connective tissue disorders
Muscle Spasms
5.3%
1/19
Musculoskeletal and connective tissue disorders
Muscular Weakness
5.3%
1/19
Musculoskeletal and connective tissue disorders
Myalgia
5.3%
1/19
Musculoskeletal and connective tissue disorders
Neck Pain
5.3%
1/19
Nervous system disorders
Headache
10.5%
2/19
Nervous system disorders
Dizziness
5.3%
1/19
Nervous system disorders
Dysarthria
5.3%
1/19
Nervous system disorders
Paraesthesia
5.3%
1/19
Nervous system disorders
Peripheral Sensory Neuropathy
5.3%
1/19
Psychiatric disorders
Anxiety
10.5%
2/19
Psychiatric disorders
Insomnia
10.5%
2/19
Psychiatric disorders
Mood Altered
5.3%
1/19
Renal and urinary disorders
Nephrolithiasis
5.3%
1/19
Renal and urinary disorders
Proteinuria
5.3%
1/19
Renal and urinary disorders
Renal Failure
5.3%
1/19
Reproductive system and breast disorders
Erectile Dysfunction
5.3%
1/19
Reproductive system and breast disorders
Menorrhagia
5.3%
1/19
Respiratory, thoracic and mediastinal disorders
Cough
5.3%
1/19
Respiratory, thoracic and mediastinal disorders
Dysphonia
5.3%
1/19
Respiratory, thoracic and mediastinal disorders
Dyspnoea Exertional
5.3%
1/19
Respiratory, thoracic and mediastinal disorders
Haemoptysis
5.3%
1/19
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal Pain
5.3%
1/19
Respiratory, thoracic and mediastinal disorders
Upper Respiratory Tract Congestion
5.3%
1/19
Skin and subcutaneous tissue disorders
Rash
26.3%
5/19
Skin and subcutaneous tissue disorders
Photosensitivity Reaction
15.8%
3/19
Skin and subcutaneous tissue disorders
Dermatitis Acneiform
10.5%
2/19
Skin and subcutaneous tissue disorders
Dry Skin
10.5%
2/19
Skin and subcutaneous tissue disorders
Acne
5.3%
1/19
Skin and subcutaneous tissue disorders
Erythema
5.3%
1/19
Skin and subcutaneous tissue disorders
Pruritus
5.3%
1/19
Skin and subcutaneous tissue disorders
Purpura
5.3%
1/19
Skin and subcutaneous tissue disorders
Rash Erythematous
5.3%
1/19
Skin and subcutaneous tissue disorders
Rash Maculo-Papular
5.3%
1/19
Skin and subcutaneous tissue disorders
Skin Exfoliation
5.3%
1/19
Vascular disorders
Hypertension
15.8%
3/19
Vascular disorders
Flushing
5.3%
1/19

Additional Information

Trial Transparency Team

Sanofi

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