Trial Outcomes & Findings for Study Evaluating Neratinib In Combination With Vinorelbine In Subjects With Advanced Or Metastatic Solid Tumors (NCT NCT00958724)
NCT ID: NCT00958724
Last Updated: 2018-06-28
Results Overview
Number of participants experiencing DLT of neratinib in combination with vinorelbine in Japanese patients.
COMPLETED
PHASE1
6 participants
From first dose date to 21st day
2018-06-28
Participant Flow
Participant milestones
| Measure |
Nera 240 + Vino 25
Neratinib 240 mg + Vinorelbine 25 mg/m\^2
|
|---|---|
|
Overall Study
STARTED
|
6
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
6
|
Reasons for withdrawal
| Measure |
Nera 240 + Vino 25
Neratinib 240 mg + Vinorelbine 25 mg/m\^2
|
|---|---|
|
Overall Study
Disease Progression
|
6
|
Baseline Characteristics
Study Evaluating Neratinib In Combination With Vinorelbine In Subjects With Advanced Or Metastatic Solid Tumors
Baseline characteristics by cohort
| Measure |
Nera 240 + Vino 25
n=6 Participants
Neratinib 240 mg + Vinorelbine 25 mg/m\^2
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
5 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=5 Participants
|
|
Age, Continuous
|
54 years
STANDARD_DEVIATION 13.37 • n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Japanese
|
6 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From first dose date to 21st dayPopulation: Safety population
Number of participants experiencing DLT of neratinib in combination with vinorelbine in Japanese patients.
Outcome measures
| Measure |
Nera 240 + Vino 25
n=6 Participants
Neratinib 240 mg + Vinorelbine 25 mg/m\^2
|
|---|---|
|
Dose Limiting Toxicity (DLT)
|
1 participants
|
SECONDARY outcome
Timeframe: From first dose date to progression or last tumor assessment, up to 40 weeks.Population: Subjects who met eligibility criteria, received at least 2 weeks of continual daily dosing of neratinib, at least 2 doses of vinorelbine, and underwent at least 1 follow-up tumor assessment at 6 weeks, ie, approximately at cycle 2. In the case of disease progression prior to 6 weeks, a clinical assessment of progressive disease was adequate.
Best Overall Response in Evaluable Population per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Outcome measures
| Measure |
Nera 240 + Vino 25
n=6 Participants
Neratinib 240 mg + Vinorelbine 25 mg/m\^2
|
|---|---|
|
Best Overall Response
Partial Response
|
1 Participants
|
|
Best Overall Response
Stable Disease >= 6 weeks
|
5 Participants
|
|
Best Overall Response
Stable Disease >= 24 weeks
|
1 Participants
|
SECONDARY outcome
Timeframe: From first response date to PD/death, up to 40 weeks.Population: Subjects who had a partial or complete response
The duration of objective response was measured from the time at which measurement criteria were met for Complete Response (CR) or Partial Response (PR) (whichever status was recorded first) until the first date on which recurrence or Progressive Disease (PD) was objectively documented, taking as reference for PD the smallest measurements recorded since the treatment started.
Outcome measures
| Measure |
Nera 240 + Vino 25
n=1 Participants
Neratinib 240 mg + Vinorelbine 25 mg/m\^2
|
|---|---|
|
Duration of Objective Response
|
12.0 weeks
Confidence Interval not estimable with only 1 subject.
|
SECONDARY outcome
Timeframe: From first dose date to progression or last tumor assessment, up to 40 weeks.Population: Safety population
Proportion of subjects who achieved complete response or partial response per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Outcome measures
| Measure |
Nera 240 + Vino 25
n=6 Participants
Neratinib 240 mg + Vinorelbine 25 mg/m\^2
|
|---|---|
|
Objective Response Rate (ORR)
|
16.7 percentage of participants
Interval 0.4 to 64.1
|
SECONDARY outcome
Timeframe: From first dose to last evaluation, up to 40 weeks.Population: Subjects who met eligibility criteria, received at least 2 weeks of continual daily dosing of neratinib and at least 2 doses of vinorelbine, and underwent at least 1 follow-up tumor assessment at 6 weeks, i.e., approximately at cycle 2. In the case of disease progression prior to 6 weeks, a clinical assessment of PD was adequate.
Number of weeks between the date of the first dose of test article and the first date of disease recurrence or progression, or death due to any cause, was documented, censored at the last evaluation, investigator assessment. Disease Progression (PD) is defined using Response Evaluation Criteria in Solid Tumors Criteria (v1.0), at least a 20% increase in the sum of the longest diameters (LD) of target lesions, taking as reference the nadir LD, meaning the smallest sum of the LDs recorded since the treatment started; or unequivocal progression of existing nontarget lesions; or the appearance of any new lesions.
Outcome measures
| Measure |
Nera 240 + Vino 25
n=6 Participants
Neratinib 240 mg + Vinorelbine 25 mg/m\^2
|
|---|---|
|
Progression Free Survival
|
18.2 weeks
Interval 18.0 to 24.1
|
SECONDARY outcome
Timeframe: Predose, and hour 1, 2, 4, 6, 8 and 24 on day 8.Population: Population for pharmacokinetic analyses consisted of all subjects in this study who received at least 1 dose of neratinib and provided samples for pharmacokinetic assessments.
AUC of Neratinib at day 8 following administration of Neratinib 240 mg in combination with Vinorelbine 25 mg/m\^2 to Japanese Subjects with Cancer.
Outcome measures
| Measure |
Nera 240 + Vino 25
n=5 Participants
Neratinib 240 mg + Vinorelbine 25 mg/m\^2
|
|---|---|
|
Area Under the Curve (AUC) Tau
|
1330 ng*hr/mL
Standard Deviation 925
|
SECONDARY outcome
Timeframe: Predose, and hour 1, 2, 4, 6, 8 and 24 on day 8.Population: Population for pharmacokinetic analyses consisted of all subjects in this study who received at least 1 dose of neratinib and provided samples for pharmacokinetic assessments.
Terminal-phase elimination half-life of Neratinib at day 8 following Administration of Neratinib 240 mg in combination with Vinorelbine 25 mg/m\^2 to Japanese Subjects with Cancer.
Outcome measures
| Measure |
Nera 240 + Vino 25
n=4 Participants
Neratinib 240 mg + Vinorelbine 25 mg/m\^2
|
|---|---|
|
Terminal-phase Elimination Half-life
|
14.37 hr
Standard Deviation 3.41
|
Adverse Events
Nera 240 + Vino 25
Serious adverse events
| Measure |
Nera 240 + Vino 25
n=6 participants at risk
Neratinib 240 mg + Vinorelbine 25 mg/m\^2
|
|---|---|
|
Infections and infestations
Peritoneal abscess
|
16.7%
1/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
Other adverse events
| Measure |
Nera 240 + Vino 25
n=6 participants at risk
Neratinib 240 mg + Vinorelbine 25 mg/m\^2
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
33.3%
2/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Blood and lymphatic system disorders
Leukopenia
|
100.0%
6/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Blood and lymphatic system disorders
Lymphopenia
|
50.0%
3/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Blood and lymphatic system disorders
Neutropenia
|
100.0%
6/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Cardiac disorders
Left ventricular dysfunction
|
16.7%
1/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Eye disorders
Keratitis
|
16.7%
1/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Gastrointestinal disorders
Abdominal pain
|
16.7%
1/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
16.7%
1/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Gastrointestinal disorders
Diarrhoea
|
100.0%
6/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Gastrointestinal disorders
Enterocolitis
|
16.7%
1/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Gastrointestinal disorders
Gastritis
|
16.7%
1/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Gastrointestinal disorders
Nausea
|
66.7%
4/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Gastrointestinal disorders
Stomatitis
|
66.7%
4/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Gastrointestinal disorders
Vomiting
|
50.0%
3/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
General disorders
Face oedema
|
16.7%
1/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
General disorders
Fatigue
|
83.3%
5/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
General disorders
Influenza like illness
|
33.3%
2/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
General disorders
Non-cardiac chest pain
|
16.7%
1/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
General disorders
Performance status decreased
|
16.7%
1/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
General disorders
Pyrexia
|
83.3%
5/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Infections and infestations
Nasopharyngitis
|
33.3%
2/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Infections and infestations
Proctitis infectious
|
16.7%
1/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Injury, poisoning and procedural complications
Lumbar vertebral fracture
|
16.7%
1/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Injury, poisoning and procedural complications
Rib fracture
|
16.7%
1/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Investigations
Alanine aminotransferase increased
|
33.3%
2/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Investigations
Aspartate aminotransferase increased
|
16.7%
1/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Investigations
Blood chloride decreased
|
16.7%
1/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Investigations
Blood creatinine increased
|
16.7%
1/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Investigations
Blood lactate dehydrogenase increased
|
16.7%
1/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Investigations
Blood sodium decreased
|
16.7%
1/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Investigations
Eastern Cooperative Oncology Group performance status worsened
|
16.7%
1/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Investigations
Electrocardiogram QT prolonged
|
16.7%
1/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Investigations
Haematocrit decreased
|
16.7%
1/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Investigations
Haemoglobin decreased
|
33.3%
2/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Investigations
Monocyte count decreased
|
16.7%
1/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Investigations
Protein urine
|
16.7%
1/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Investigations
Weight decreased
|
50.0%
3/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
83.3%
5/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
16.7%
1/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
16.7%
1/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
16.7%
1/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Nervous system disorders
Dysgeusia
|
16.7%
1/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
50.0%
3/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Psychiatric disorders
Insomnia
|
33.3%
2/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Respiratory, thoracic and mediastinal disorders
Aspiration
|
16.7%
1/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
16.7%
1/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
16.7%
1/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
16.7%
1/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Respiratory, thoracic and mediastinal disorders
Laryngeal pain
|
16.7%
1/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
16.7%
1/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Skin and subcutaneous tissue disorders
Decubitus ulcer
|
16.7%
1/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
16.7%
1/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Skin and subcutaneous tissue disorders
Rash
|
50.0%
3/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Skin and subcutaneous tissue disorders
Skin fissures
|
16.7%
1/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
|
Vascular disorders
Vasculitis
|
16.7%
1/6 • From first dose through 28 days after last dose, up to 40 weeks.
|
Additional Information
Senior Director, Clinical Operations
Puma Biotechnology, Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60