Trial Outcomes & Findings for Addition of Vandetanib to Standard Therapy Pegliposomal Doxorubicin (PLD) (NCT NCT00862836)
NCT ID: NCT00862836
Last Updated: 2016-10-10
Results Overview
Number of participants with at least 1 adverse event of grade 3 or higher (CTCAE grade 3=severe, CTCAE grade 4=life threatening/disabling, CTCAE grade 5=death, as defined by National Cancer Institute CTCAE, Version 3)
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
15 participants
Primary outcome timeframe
From date of registration (Informed Consent Form completed) to date of last vist, up to 18 months.
Results posted on
2016-10-10
Participant Flow
Phase I of the trial consisted of a safety run-in phase of 10 patients with histologically confirmed, epithelial ovarian carcinoma, cancer of the fallopian tube or the peritoneum refractory or partially sensitive to platinum-based therapy evaluable for at least 2 cycles. Phase II of the trial was not conducted.
Participant milestones
| Measure |
Vandetanib 100 mg
Once daily oral Vandetanib 100 mg added to standard therapy (pegylated liposomal doxorubicin 50 mg/m2 iv every 4 weeks)
|
|---|---|
|
Overall Study
STARTED
|
15
|
|
Overall Study
Evaluable for Safety/Toxicity
|
14
|
|
Overall Study
Evaluable for Activity (Tumour Response)
|
10
|
|
Overall Study
COMPLETED
|
14
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Vandetanib 100 mg
Once daily oral Vandetanib 100 mg added to standard therapy (pegylated liposomal doxorubicin 50 mg/m2 iv every 4 weeks)
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
Baseline Characteristics
Addition of Vandetanib to Standard Therapy Pegliposomal Doxorubicin (PLD)
Baseline characteristics by cohort
| Measure |
Vandetanib 100 mg
n=15 Participants
Once daily oral Vandetanib 100 mg added to standard therapy (pegylated liposomal doxorubicin 50 mg/m2 iv every 4 weeks)
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
12 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From date of registration (Informed Consent Form completed) to date of last vist, up to 18 months.Number of participants with at least 1 adverse event of grade 3 or higher (CTCAE grade 3=severe, CTCAE grade 4=life threatening/disabling, CTCAE grade 5=death, as defined by National Cancer Institute CTCAE, Version 3)
Outcome measures
| Measure |
Vandetanib 100 mg
n=14 Participants
Once daily oral Vandetanib 100 mg added to standard therapy (pegylated liposomal doxorubicin 50 mg/m2 iv every 4 weeks)
|
|---|---|
|
Description (on the Basis of the Safety Set): Safety and Tolerability by Means of the Incidence and Type of Adverse Events (AEs).
|
9 Participants
|
PRIMARY outcome
Timeframe: From date of registration (Informed Consent Form completed) to date of last vist, up to 18 months.Number of patients with elevated liver enzymes grade 3 (CTCAE grade 3=severe, CTCAE grade 4=life threatening).
Outcome measures
| Measure |
Vandetanib 100 mg
n=14 Participants
Once daily oral Vandetanib 100 mg added to standard therapy (pegylated liposomal doxorubicin 50 mg/m2 iv every 4 weeks)
|
|---|---|
|
Description (on the Basis of the Safety Set): Safety and Tolerability by Means of Clinically Significant Laboratory Abnormalities.
|
3 Participants
|
PRIMARY outcome
Timeframe: From date of registration (Informed Consent Form completed) to date of last vist, up to 18 months.Number of participants with dermatologic skin reactions grade 3/4 (CTCAE grade 3= severe, CTCAE grade 4=life threatening)
Outcome measures
| Measure |
Vandetanib 100 mg
n=14 Participants
Once daily oral Vandetanib 100 mg added to standard therapy (pegylated liposomal doxorubicin 50 mg/m2 iv every 4 weeks)
|
|---|---|
|
Description (on the Basis of the Safety Set): Safety and Tolerability by Means of the Incidence and Type of Adverse Events (AEs). Number of Participants With Dermatologic Skin Reactions Grade 3/4.
|
5 Participants
|
PRIMARY outcome
Timeframe: From date of registration (Informed Consent Form completed) to date of last vist, up to 18 months.Number of participants with palmar-plantar erythrodysesthesia (PPE) grade 3/4 (CTCAE grade 3=severe skin changes with pain, CTCAE grade 4=life threatening).
Outcome measures
| Measure |
Vandetanib 100 mg
n=14 Participants
Once daily oral Vandetanib 100 mg added to standard therapy (pegylated liposomal doxorubicin 50 mg/m2 iv every 4 weeks)
|
|---|---|
|
Description (on the Basis of the Safety Set): Safety and Tolerability by Means of the Incidence and Type of Adverse Events (AEs). Number of Participants With Palmar-plantar Erythrodysesthesia (PPE) Grade 3/4.
|
5 Participants
|
PRIMARY outcome
Timeframe: From date of registration (Informed Consent Form completed) to date of last vist, up to 18 months.Number of participants with mucositis grade 3 (CTCAE grade 3=severe pain interfering with oral intake)
Outcome measures
| Measure |
Vandetanib 100 mg
n=14 Participants
Once daily oral Vandetanib 100 mg added to standard therapy (pegylated liposomal doxorubicin 50 mg/m2 iv every 4 weeks)
|
|---|---|
|
Description (on the Basis of the Safety Set): Safety and Tolerability by Means of the Incidence and Type of Adverse Events (AEs). Number of Participants With Mucositis Grade 3.
|
2 Participants
|
PRIMARY outcome
Timeframe: From date of registration (Informed Consent Form completed) to date of last vist, up to 18 months.Number of participants with neutropenia grade 3/4 (CTCAE grade 3=severe, CTCAE grade 4=life threatening).
Outcome measures
| Measure |
Vandetanib 100 mg
n=14 Participants
Once daily oral Vandetanib 100 mg added to standard therapy (pegylated liposomal doxorubicin 50 mg/m2 iv every 4 weeks)
|
|---|---|
|
Description (on the Basis of the Safety Set): Safety and Tolerability by Means of Clinically Significant Laboratory Abnormalities. Number of Participants With Neutropenia Grade 3/4.
|
2 Participants
|
SECONDARY outcome
Timeframe: From date of registration (Informed Consent Form completed) until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months.Progression Free Survival: Progression is defined using RECIST, as a measurable increase of at least 20% in the sum of longest diameters of target lesions or unequivocal progression of non-target lesions, or the appearance of new lesions, since baseline.
Outcome measures
| Measure |
Vandetanib 100 mg
n=10 Participants
Once daily oral Vandetanib 100 mg added to standard therapy (pegylated liposomal doxorubicin 50 mg/m2 iv every 4 weeks)
|
|---|---|
|
Evaluation (for ITT Set): Clinical Activity of Once Daily Oral Vandetanib 100 mg When Added to Standard Therapy (See Above), by Assessment of Progression Free Survival (PFS).
|
6.7 Months
Interval 0.87 to 13.73
|
SECONDARY outcome
Timeframe: From date of registration (Informed Consent Form completed) until the date of death.Median overall survival (OS)
Outcome measures
| Measure |
Vandetanib 100 mg
n=10 Participants
Once daily oral Vandetanib 100 mg added to standard therapy (pegylated liposomal doxorubicin 50 mg/m2 iv every 4 weeks)
|
|---|---|
|
Evaluation (for ITT Set): Clinical Activity of Once Daily Oral Vandetanib 100 mg When Added to Standard Therapy (See Above), by Assessment of Overall Survival (OS).
|
11.1 Months
Interval 2.17 to 14.93
|
Adverse Events
Vandetanib 100 mg
Serious events: 3 serious events
Other events: 14 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Vandetanib 100 mg
n=14 participants at risk
Once daily oral Vandetanib 100 mg added to standard therapy (pegylated liposomal doxorubicin 50 mg/m2 iv every 4 weeks)
|
|---|---|
|
Cardiac disorders
Arrhythmia
|
7.1%
1/14
|
|
Gastrointestinal disorders
Abdominal pain
|
7.1%
1/14
|
|
Gastrointestinal disorders
Ascites
|
7.1%
1/14
|
|
Gastrointestinal disorders
Ileus
|
7.1%
1/14
|
|
Gastrointestinal disorders
Nausea
|
7.1%
1/14
|
|
Gastrointestinal disorders
Vomiting
|
7.1%
1/14
|
|
General disorders
General physical health deterioration
|
7.1%
1/14
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
7.1%
1/14
|
Other adverse events
| Measure |
Vandetanib 100 mg
n=14 participants at risk
Once daily oral Vandetanib 100 mg added to standard therapy (pegylated liposomal doxorubicin 50 mg/m2 iv every 4 weeks)
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
7.1%
1/14
|
|
Blood and lymphatic system disorders
Leukopenia
|
7.1%
1/14
|
|
Blood and lymphatic system disorders
Neutropenia
|
7.1%
1/14
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
7.1%
1/14
|
|
Blood and lymphatic system disorders
Thrombocytosis
|
7.1%
1/14
|
|
Cardiac disorders
Angina pectoris
|
7.1%
1/14
|
|
Cardiac disorders
Tachyarrhythmia
|
7.1%
1/14
|
|
Gastrointestinal disorders
Diarrhoea
|
50.0%
7/14
|
|
Gastrointestinal disorders
Nausea
|
50.0%
7/14
|
|
Gastrointestinal disorders
Constipation
|
28.6%
4/14
|
|
Gastrointestinal disorders
Vomiting
|
28.6%
4/14
|
|
Gastrointestinal disorders
Abdominal pain
|
21.4%
3/14
|
|
Gastrointestinal disorders
Dyspepsia
|
21.4%
3/14
|
|
Gastrointestinal disorders
Stomatitis
|
21.4%
3/14
|
|
Gastrointestinal disorders
Dysphagia
|
14.3%
2/14
|
|
Gastrointestinal disorders
Oesophagitis
|
14.3%
2/14
|
|
Gastrointestinal disorders
Flatulence
|
7.1%
1/14
|
|
Gastrointestinal disorders
Gingivitis
|
7.1%
1/14
|
|
Gastrointestinal disorders
Oesophageal pain
|
7.1%
1/14
|
|
General disorders
Fatigue
|
42.9%
6/14
|
|
General disorders
Mucosal inflammation
|
42.9%
6/14
|
|
General disorders
Chills
|
7.1%
1/14
|
|
General disorders
Mucosal dryness
|
7.1%
1/14
|
|
General disorders
Oedema peripheral
|
7.1%
1/14
|
|
Immune system disorders
Hypersensitivity
|
7.1%
1/14
|
|
Infections and infestations
Localised infection
|
7.1%
1/14
|
|
Infections and infestations
Nasopharyngitis
|
7.1%
1/14
|
|
Infections and infestations
Urinary tract infection
|
7.1%
1/14
|
|
Investigations
Gamma-glutamyltransferase
|
42.9%
6/14
|
|
Infections and infestations
Rhinitis
|
7.1%
1/14
|
|
Investigations
Aspartate aminotransferase
|
35.7%
5/14
|
|
Investigations
White blood cell count
|
35.7%
5/14
|
|
Investigations
Alanine aminotransferase
|
28.6%
4/14
|
|
Investigations
Blood alkaline phosphatase
|
28.6%
4/14
|
|
Investigations
Blood creatinine
|
21.4%
3/14
|
|
Investigations
Blood lactate dehydrogenase
|
21.4%
3/14
|
|
Investigations
Haemoglobin
|
21.4%
3/14
|
|
Investigations
Blood glucose
|
14.3%
2/14
|
|
Investigations
Monocyte count
|
14.3%
2/14
|
|
Investigations
Protein total
|
14.3%
2/14
|
|
Investigations
Activated partial thromboplastin time
|
7.1%
1/14
|
|
Investigations
Alanine aminotransferase increased
|
7.1%
1/14
|
|
Investigations
Aspartate aminotransferase increased
|
7.1%
1/14
|
|
Investigations
Blood bilirubin
|
7.1%
1/14
|
|
Investigations
Blood calcium
|
7.1%
1/14
|
|
Investigations
Blood chloride
|
7.1%
1/14
|
|
Investigations
Blood glucose increased
|
7.1%
1/14
|
|
Investigations
Blood lactate dehydrogenase increased
|
7.1%
1/14
|
|
Investigations
Blood magnesium decreased
|
7.1%
1/14
|
|
Investigations
Blood potassium
|
7.1%
1/14
|
|
Investigations
Haematocrit
|
7.1%
1/14
|
|
Investigations
Haematocrit decreased
|
7.1%
1/14
|
|
Investigations
Haemoglobin decreased
|
7.1%
1/14
|
|
Investigations
Monocyte count decreased
|
7.1%
1/14
|
|
Investigations
Neutrophil count
|
7.1%
1/14
|
|
Investigations
Neutrophil count increased
|
7.1%
1/14
|
|
Investigations
Prothrombin time
|
7.1%
1/14
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
14.3%
2/14
|
|
Metabolism and nutrition disorders
Decreased appetite
|
7.1%
1/14
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
7.1%
1/14
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
7.1%
1/14
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
7.1%
1/14
|
|
Metabolism and nutrition disorders
Hypoproteinaemia
|
7.1%
1/14
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
7.1%
1/14
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
7.1%
1/14
|
|
Nervous system disorders
Headache
|
28.6%
4/14
|
|
Nervous system disorders
Peripheral sensory neuropath
|
7.1%
1/14
|
|
Psychiatric disorders
Sleep disorder
|
14.3%
2/14
|
|
Psychiatric disorders
Insomnia
|
7.1%
1/14
|
|
Psychiatric disorders
Chromaturia
|
7.1%
1/14
|
|
Renal and urinary disorders
Renal pain
|
7.1%
1/14
|
|
Reproductive system and breast disorders
Breast pain
|
7.1%
1/14
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
21.4%
3/14
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
14.3%
2/14
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
7.1%
1/14
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
7.1%
1/14
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
7.1%
1/14
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
50.0%
7/14
|
|
Skin and subcutaneous tissue disorders
Rash
|
28.6%
4/14
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
14.3%
2/14
|
|
Skin and subcutaneous tissue disorders
Acne
|
7.1%
1/14
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
7.1%
1/14
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
7.1%
1/14
|
|
Skin and subcutaneous tissue disorders
Eczema
|
7.1%
1/14
|
|
Skin and subcutaneous tissue disorders
Erythema
|
7.1%
1/14
|
|
Skin and subcutaneous tissue disorders
Heat rash
|
7.1%
1/14
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
7.1%
1/14
|
|
Skin and subcutaneous tissue disorders
Skin toxicity
|
7.1%
1/14
|
|
Vascular disorders
Flushing
|
7.1%
1/14
|
|
Vascular disorders
Hot flush
|
7.1%
1/14
|
|
Investigations
International normalised ratio
|
7.1%
1/14
|
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