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Trial record 30 of 42 for:    Malignant Hyperthermia 5

A Study Of Neratinib (HKI-272) And Capecitabine In Japanese With Solid Tumor

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ClinicalTrials.gov Identifier: NCT01128842
Recruitment Status : Completed
First Posted : May 24, 2010
Results First Posted : December 19, 2018
Last Update Posted : December 19, 2018
Sponsor:
Information provided by (Responsible Party):
Puma Biotechnology, Inc.

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Advanced Malignant Solid Tumors
Interventions Drug: Neratinib
Drug: Capecitabine
Enrollment 7
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Neratinib + Capecitabine
Hide Arm/Group Description Neratinib: 240 mg once daily by mouth, Capecitabine: 1500 mg/m^2 twice daily.
Period Title: Overall Study
Started 7
Completed 0
Not Completed 7
Reason Not Completed
Adverse Event             1
Disease Progression             6
Arm/Group Title Neratinib + Capecitabine
Hide Arm/Group Description Neratinib: 240 mg, continuous once daily by mouth Capecitabine: 1500 mg/m^2 twice daily by mouth
Overall Number of Baseline Participants 7
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants
<=18 years
0
   0.0%
Between 18 and 65 years
6
  85.7%
>=65 years
1
  14.3%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 7 participants
52.43  (11.27)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants
Female
4
  57.1%
Male
3
  42.9%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Japanese Number Analyzed 7 participants
7
 100.0%
1.Primary Outcome
Title Dose Limiting Toxicity (DLT) - Percentage of Participants With DLT Events
Hide Description 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.
Time Frame From first dose date to day 21.
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population was defined as all subjects who received at least 1 dose of investigational product (neratinib and/or capecitabine).
Arm/Group Title Neratinib + Capecitabine
Hide Arm/Group Description:
Neratinib: 240 mg once daily by mouth, Capecitabine: 1500 mg/m^2 twice daily by mouth.
Overall Number of Participants Analyzed 7
Measure Type: Count of Participants
Unit of Measure: Participants
1
  14.3%
2.Primary Outcome
Title Tolerated Dose
Hide Description

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.

Time Frame From first dose date to day 21.
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population was defined as all subjects who received at least 1 dose of investigational product (neratinib and/or capecitabine).
Arm/Group Title Neratinib + Capecitabine
Hide Arm/Group Description:
Neratinib: 240 mg once daily by mouth, Capecitabine: 1500 mg/m^2 twice daily by mouth.
Overall Number of Participants Analyzed 7
Measure Type: Number
Unit of Measure: mg
240
3.Secondary Outcome
Title Best Overall Response
Hide Description 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.
Time Frame From first dose date to progression or last tumor assessment, up to 41 weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Neratinib + Capecitabine
Hide Arm/Group Description:
Neratinib: 240 mg once daily by mouth, Capecitabine: 1500 mg/m^2 twice daily by mouth.
Overall Number of Participants Analyzed 7
Measure Type: Count of Participants
Unit of Measure: Participants
Partial Response
1
  14.3%
Stable Disease
4
  57.1%
Progressive Disease
2
  28.6%
4.Secondary Outcome
Title Objective Response Rate
Hide Description 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.
Time Frame From first dose date to progression or last tumor assessment, up to 41 weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Neratinib + Capecitabine
Hide Arm/Group Description:
Neratinib: 240 mg once daily by mouth, Capecitabine: 1500 mg/m^2 twice daily by mouth.
Overall Number of Participants Analyzed 7
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
14.3
(0.40 to 57.9)
5.Secondary Outcome
Title Progression Free Survival
Hide Description 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.
Time Frame From first dose date to PD or death, up to 41 weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Neratinib + Capecitabine
Hide Arm/Group Description:
Neratinib: 240 mg once daily by mouth, Capecitabine: 1500 mg/m^2 twice daily by mouth.
Overall Number of Participants Analyzed 7
Median (95% Confidence Interval)
Unit of Measure: weeks
15.6
(5.4 to 36.1)
6.Secondary Outcome
Title Area Under the Curve (AUC) of Neratinib in Combination With Capecitabine
Hide Description 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.
Time Frame At 1, 2, 4, 6, 8 and 21-24 hours after dose on day 14.
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic population was defined as all subjects who received at least 1 dose of investigational product (neratinib and/or capecitabine).
Arm/Group Title Neratinib + Capecitabine
Hide Arm/Group Description:
Neratinib: 240 mg once daily by mouth, Capecitabine: 1500 mg/m^2 twice daily by mouth.
Overall Number of Participants Analyzed 7
Mean (Standard Deviation)
Unit of Measure: ng*hr/mL
1070  (619)
7.Secondary Outcome
Title Maximum Plasma Concentration of Neratinib in Combination With Capecitabine
Hide Description 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.
Time Frame Measured at 1, 2, 4, 6, 8 and 21-24 hours after dose on day 14.
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic population was defined as all subjects who received at least 1 dose of investigational product (neratinib and/or capecitabine).
Arm/Group Title Neratinib + Capecitabine
Hide Arm/Group Description:
Neratinib: 240 mg once daily by mouth, Capecitabine: 1500 mg/m^2 twice daily by mouth
Overall Number of Participants Analyzed 7
Mean (Standard Deviation)
Unit of Measure: ng/mL
61.9  (32.0)
Time Frame From first dose through 28 days after last dose, up to 41 weeks.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Neratinib + Capecitabine
Hide Arm/Group Description Neratinib: 240 mg once daily by mouth, Capecitabine: 1500 mg/m^2 twice daily by mouth.
All-Cause Mortality
Neratinib + Capecitabine
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Neratinib + Capecitabine
Affected / at Risk (%)
Total   1/7 (14.29%) 
Gastrointestinal disorders   
Diarrhoea  1  1/7 (14.29%) 
Nausea  1  1/7 (14.29%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (17.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Neratinib + Capecitabine
Affected / at Risk (%)
Total   7/7 (100.00%) 
Blood and lymphatic system disorders   
Anaemia  1  1/7 (14.29%) 
Neutropenia  1  2/7 (28.57%) 
Thrombocytopenia  1  1/7 (14.29%) 
Gastrointestinal disorders   
Abdominal pain upper  1  1/7 (14.29%) 
Cheilitis  1  2/7 (28.57%) 
Diarrhoea  1  7/7 (100.00%) 
Nausea  1  4/7 (57.14%) 
Oesophagitis  1  1/7 (14.29%) 
Proctalgia  1  1/7 (14.29%) 
Stomatitis  1  2/7 (28.57%) 
Vomiting  1  2/7 (28.57%) 
General disorders   
Asthenia  1  1/7 (14.29%) 
Fatigue  1  5/7 (71.43%) 
Mucosal inflammation  1  1/7 (14.29%) 
Hepatobiliary disorders   
Hyperbilirubinaemia  1  1/7 (14.29%) 
Infections and infestations   
Cystitis  1  1/7 (14.29%) 
Nasopharyngitis  1  1/7 (14.29%) 
Paronychia  1  4/7 (57.14%) 
Tinea infection  1  1/7 (14.29%) 
Upper respiratory tract infection  1  1/7 (14.29%) 
Investigations   
Alanine aminotransferase increased  1  1/7 (14.29%) 
Aspartate aminotransferase increased  1  1/7 (14.29%) 
Electrocardiogram QT prolonged  1  1/7 (14.29%) 
Weight decreased  1  5/7 (71.43%) 
Metabolism and nutrition disorders   
Decreased appetite  1  5/7 (71.43%) 
Dehydration  1  1/7 (14.29%) 
Hypokalaemia  1  1/7 (14.29%) 
Hypophosphataemia  1  1/7 (14.29%) 
Musculoskeletal and connective tissue disorders   
Pain in extremity  1  1/7 (14.29%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Cancer pain  1  1/7 (14.29%) 
Nervous system disorders   
Neuropathy peripheral  1  1/7 (14.29%) 
Peripheral sensory neuropathy  1  1/7 (14.29%) 
Psychiatric disorders   
Anxiety  1  2/7 (28.57%) 
Insomnia  1  2/7 (28.57%) 
Renal and urinary disorders   
Haematuria  1  1/7 (14.29%) 
Proteinuria  1  1/7 (14.29%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  2/7 (28.57%) 
Productive cough  1  2/7 (28.57%) 
Respiratory tract haemorrhage  1  1/7 (14.29%) 
Skin and subcutaneous tissue disorders   
Dry skin  1  1/7 (14.29%) 
Palmar-plantar erythrodysaesthesia syndrome  1  4/7 (57.14%) 
Rash  1  6/7 (85.71%) 
Skin exfoliation  1  1/7 (14.29%) 
Skin hyperpigmentation  1  1/7 (14.29%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (17.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Director, Clinical Operations
Organization: Puma Biotechnology, Inc.
Phone: +1 (424) 248-6500
EMail: clinicaltrials@pumabiotechnology.com
Layout table for additonal information
Responsible Party: Puma Biotechnology, Inc.
ClinicalTrials.gov Identifier: NCT01128842     History of Changes
Other Study ID Numbers: 3144A1-1122 / B1891018
First Submitted: May 20, 2010
First Posted: May 24, 2010
Results First Submitted: August 10, 2017
Results First Posted: December 19, 2018
Last Update Posted: December 19, 2018