Trial Outcomes & Findings for A Study Of Neratinib (HKI-272) And Capecitabine In Japanese With Solid Tumor (NCT NCT01128842)
NCT ID: NCT01128842
Last Updated: 2018-12-19
Results Overview
DLT was defined as 1. Grade 3 or 4 non-hematologic toxicity (exceptions listed below as a.-c.), a. Grade 3 asthenia was NOT considered to be a DLT UNLESS it lasted \>3 days. b. Grade 3 nausea or vomiting was NOT considered to be a DLT UNLESS the subject was already receiving optimal medical therapy. c. Grade 3 or 4 infection was NOT considered to be a DLT UNLESS it is associated with grade 3 or 4 neutropenia. 2. Grade 3 diarrhea that lasted \>2 days while the subject was on optimal medical therapy or that was associated with fever (greater than or equal 38.0 ºC) or grade 3 dehydration. 3. Grade 4 neutropenia lasting ≥3 days or grade 4 febrile neutropenia. 4. Grade 4 thrombocytopenia lasting ≥3 days or complicated with bleeding or requiring platelet transfusion. 5. Delayed recovery (to National Cancer Institute \[NCI\] grade 1 or less, or baseline) from any of the toxicities listed above (items 1-4), that was related to study drug, and that delayed the next dose by more than 3 weeks.
COMPLETED
PHASE1
7 participants
From first dose date to day 21.
2018-12-19
Participant Flow
Participant milestones
| Measure |
Neratinib + Capecitabine
Neratinib: 240 mg once daily by mouth, Capecitabine: 1500 mg/m\^2 twice daily.
|
|---|---|
|
Overall Study
STARTED
|
7
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
7
|
Reasons for withdrawal
| Measure |
Neratinib + Capecitabine
Neratinib: 240 mg once daily by mouth, Capecitabine: 1500 mg/m\^2 twice daily.
|
|---|---|
|
Overall Study
Adverse Event
|
1
|
|
Overall Study
Disease Progression
|
6
|
Baseline Characteristics
A Study Of Neratinib (HKI-272) And Capecitabine In Japanese With Solid Tumor
Baseline characteristics by cohort
| Measure |
Neratinib + Capecitabine
n=7 Participants
Neratinib: 240 mg, continuous once daily by mouth Capecitabine: 1500 mg/m\^2 twice daily by mouth
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
6 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=5 Participants
|
|
Age, Continuous
|
52.43 years
STANDARD_DEVIATION 11.27 • n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Japanese
|
7 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From first dose date to day 21.Population: The safety population was defined as all subjects who received at least 1 dose of investigational product (neratinib and/or capecitabine).
DLT was defined as 1. Grade 3 or 4 non-hematologic toxicity (exceptions listed below as a.-c.), a. Grade 3 asthenia was NOT considered to be a DLT UNLESS it lasted \>3 days. b. Grade 3 nausea or vomiting was NOT considered to be a DLT UNLESS the subject was already receiving optimal medical therapy. c. Grade 3 or 4 infection was NOT considered to be a DLT UNLESS it is associated with grade 3 or 4 neutropenia. 2. Grade 3 diarrhea that lasted \>2 days while the subject was on optimal medical therapy or that was associated with fever (greater than or equal 38.0 ºC) or grade 3 dehydration. 3. Grade 4 neutropenia lasting ≥3 days or grade 4 febrile neutropenia. 4. Grade 4 thrombocytopenia lasting ≥3 days or complicated with bleeding or requiring platelet transfusion. 5. Delayed recovery (to National Cancer Institute \[NCI\] grade 1 or less, or baseline) from any of the toxicities listed above (items 1-4), that was related to study drug, and that delayed the next dose by more than 3 weeks.
Outcome measures
| Measure |
Neratinib + Capecitabine
n=7 Participants
Neratinib: 240 mg once daily by mouth, Capecitabine: 1500 mg/m\^2 twice daily by mouth.
|
|---|---|
|
Dose Limiting Toxicity (DLT) - Percentage of Participants With DLT Events
|
1 Participants
|
PRIMARY outcome
Timeframe: From first dose date to day 21.Population: The safety population was defined as all subjects who received at least 1 dose of investigational product (neratinib and/or capecitabine).
Six subjects will be initially enrolled (neratinib 240 mg/day; capecitabine 1500 mg/m²/day on days 1 through 14). AEs and DLTs will be assessed from the first dose of investigational product through day 21. Based on the DLT rate in these first 6 subjects, dose tolerability will be confirmed as follows: If ≤1 of the first 6 evaluable subjects experience a DLT by day 21, then this dose is considered tolerable, and enrollment will stop. If ≥3 of the first 6 evaluable subjects experience a DLT by day 21, this dose is considered intolerable. If 2 of the first 6 evaluable subjects experience a DLT by day 21, then an additional 4 subjects will be enrolled at the same dose level. If a total of 10 subjects are enrolled, then the tolerability will be confirmed as follows: If ≤3 of the total 10 subjects experience a DLT by day 21, then this dose will be considered tolerable. If ≥4 of the total 10 subjects experience a DLT by day 21, then the dose will be considered intolerable.
Outcome measures
| Measure |
Neratinib + Capecitabine
n=7 Participants
Neratinib: 240 mg once daily by mouth, Capecitabine: 1500 mg/m\^2 twice daily by mouth.
|
|---|---|
|
Tolerated Dose
|
240 mg
|
SECONDARY outcome
Timeframe: From first dose date to progression or last tumor assessment, up to 41 weeks.Population: All subjects who met Inclusion and Exclusion criteria, received at least 2 weeks of Investigational Product, and underwent at least 1 Follow Up (FU) tumor assessment at approximately cycle 2 (week 6). Subjects who died or had PD including symptomatic deterioration before the scheduled FU tumor assessment were included in the evaluable population.
Number of participants with Partial Response (PR) or Complete Response (CR) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) (v1.0) criteria. CR: Disappearance of all lesions; PR: at least a 30% decrease in the sum of longest diameters (SLD) of target lesions, taking as reference the baseline SLD; Progressive Disease (PD): at least a 20% increase in the SLD of target lesions, taking as reference the nadir longest diameter, meaning the smallest SLDs recorded since the treatment started, or the appearance of 1 or more new lesions, or unequivocal progression of existing nontarget lesions; and stable disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SLD since treatment started.
Outcome measures
| Measure |
Neratinib + Capecitabine
n=7 Participants
Neratinib: 240 mg once daily by mouth, Capecitabine: 1500 mg/m\^2 twice daily by mouth.
|
|---|---|
|
Best Overall Response
Partial Response
|
1 Participants
|
|
Best Overall Response
Stable Disease
|
4 Participants
|
|
Best Overall Response
Progressive Disease
|
2 Participants
|
SECONDARY outcome
Timeframe: From first dose date to progression or last tumor assessment, up to 41 weeks.Population: All subjects who met Inclusion and Exclusion criteria, received at least 2 weeks of Investigational Product, and underwent at least 1 Follow Up (FU) tumor assessment at approximately cycle 2 (week 6). Subjects who died or had PD including symptomatic deterioration before the scheduled FU tumor assessment were included in the evaluable population.
Percentage of participants with partial response (PR) or complete response (CR) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v.1.0: CR, disappearance of all target lesions; PR, \>=30% decrease in the sum of the longest diameter of target lesions; and Non Progressive Disease (PD) for non-target lesions, and no new lesions.
Outcome measures
| Measure |
Neratinib + Capecitabine
n=7 Participants
Neratinib: 240 mg once daily by mouth, Capecitabine: 1500 mg/m\^2 twice daily by mouth.
|
|---|---|
|
Objective Response Rate
|
14.3 percentage of participants
Interval 0.4 to 57.9
|
SECONDARY outcome
Timeframe: From first dose date to PD or death, up to 41 weeks.Population: All subjects who met Inclusion and Exclusion criteria, received at least 2 weeks of Investigational Product, and underwent at least 1 Follow Up (FU) tumor assessment at approximately cycle 2 (week 6). Subjects who died or had PD including symptomatic deterioration before the scheduled FU tumor assessment were included in the evaluable population.
Number of weeks between the date of the first dose of test article and the first date of disease recurrence or disease progression (PD), or death due to any cause, was documented, censored at the last evaluation, investigator assessment. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (v1.0), as 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 |
Neratinib + Capecitabine
n=7 Participants
Neratinib: 240 mg once daily by mouth, Capecitabine: 1500 mg/m\^2 twice daily by mouth.
|
|---|---|
|
Progression Free Survival
|
15.6 weeks
Interval 5.4 to 36.1
|
SECONDARY outcome
Timeframe: At 1, 2, 4, 6, 8 and 21-24 hours after dose on day 14.Population: The pharmacokinetic population was defined as all subjects who received at least 1 dose of investigational product (neratinib and/or capecitabine).
AUC of Neratinib at day 14 following Administration of Neratinib 240 mg in combination with Capecitabine 1500 mg/m\^2 per day to Japanese Subjects with Cancer.
Outcome measures
| Measure |
Neratinib + Capecitabine
n=7 Participants
Neratinib: 240 mg once daily by mouth, Capecitabine: 1500 mg/m\^2 twice daily by mouth.
|
|---|---|
|
Area Under the Curve (AUC) of Neratinib in Combination With Capecitabine
|
1070 ng*hr/mL
Standard Deviation 619
|
SECONDARY outcome
Timeframe: Measured at 1, 2, 4, 6, 8 and 21-24 hours after dose on day 14.Population: The pharmacokinetic population was defined as all subjects who received at least 1 dose of investigational product (neratinib and/or capecitabine).
Maximum plasma concentration (nanograms/milliliter) of Neratinib at day 14 following Administration of Neratinib 240 mg in combination with Capecitabine 1500 mg/m\^2 per day to Japanese Subjects with Cancer.
Outcome measures
| Measure |
Neratinib + Capecitabine
n=7 Participants
Neratinib: 240 mg once daily by mouth, Capecitabine: 1500 mg/m\^2 twice daily by mouth.
|
|---|---|
|
Maximum Plasma Concentration of Neratinib in Combination With Capecitabine
|
61.9 ng/mL
Standard Deviation 32.0
|
Adverse Events
Neratinib + Capecitabine
Serious adverse events
| Measure |
Neratinib + Capecitabine
n=7 participants at risk
Neratinib: 240 mg once daily by mouth, Capecitabine: 1500 mg/m\^2 twice daily by mouth.
|
|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
14.3%
1/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
Gastrointestinal disorders
Nausea
|
14.3%
1/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
Other adverse events
| Measure |
Neratinib + Capecitabine
n=7 participants at risk
Neratinib: 240 mg once daily by mouth, Capecitabine: 1500 mg/m\^2 twice daily by mouth.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
14.3%
1/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
Blood and lymphatic system disorders
Neutropenia
|
28.6%
2/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
14.3%
1/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
14.3%
1/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
Gastrointestinal disorders
Cheilitis
|
28.6%
2/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
Gastrointestinal disorders
Diarrhoea
|
100.0%
7/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
Gastrointestinal disorders
Nausea
|
57.1%
4/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
Gastrointestinal disorders
Oesophagitis
|
14.3%
1/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
Gastrointestinal disorders
Proctalgia
|
14.3%
1/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
Gastrointestinal disorders
Stomatitis
|
28.6%
2/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
Gastrointestinal disorders
Vomiting
|
28.6%
2/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
General disorders
Asthenia
|
14.3%
1/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
General disorders
Fatigue
|
71.4%
5/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
General disorders
Mucosal inflammation
|
14.3%
1/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
14.3%
1/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
Infections and infestations
Cystitis
|
14.3%
1/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
Infections and infestations
Nasopharyngitis
|
14.3%
1/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
Infections and infestations
Paronychia
|
57.1%
4/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
Infections and infestations
Tinea infection
|
14.3%
1/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
Infections and infestations
Upper respiratory tract infection
|
14.3%
1/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
Investigations
Alanine aminotransferase increased
|
14.3%
1/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
Investigations
Aspartate aminotransferase increased
|
14.3%
1/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
Investigations
Electrocardiogram QT prolonged
|
14.3%
1/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
Investigations
Weight decreased
|
71.4%
5/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
71.4%
5/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
Metabolism and nutrition disorders
Dehydration
|
14.3%
1/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
14.3%
1/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
14.3%
1/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
14.3%
1/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
|
14.3%
1/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
Nervous system disorders
Neuropathy peripheral
|
14.3%
1/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
14.3%
1/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
Psychiatric disorders
Anxiety
|
28.6%
2/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
Psychiatric disorders
Insomnia
|
28.6%
2/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
Renal and urinary disorders
Haematuria
|
14.3%
1/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
Renal and urinary disorders
Proteinuria
|
14.3%
1/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
28.6%
2/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
28.6%
2/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory tract haemorrhage
|
14.3%
1/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
14.3%
1/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
57.1%
4/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
Skin and subcutaneous tissue disorders
Rash
|
85.7%
6/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
Skin and subcutaneous tissue disorders
Skin exfoliation
|
14.3%
1/7 • From first dose through 28 days after last dose, up to 41 weeks.
|
|
Skin and subcutaneous tissue disorders
Skin hyperpigmentation
|
14.3%
1/7 • From first dose through 28 days after last dose, up to 41 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