Advanced Malignant Solid TumorsPhase 1NCT01128842
A Study Of Neratinib (HKI-272) And Capecitabine In Japanese With Solid Tumor
A Phase 1 study testing Neratinib and Capecitabine in people with Advanced Malignant Solid Tumors, run by Puma Biotechnology, Inc. at 2 sites in Japan.
Trial summary
This is an open-label, phase 1 study of a single cohort of neratinib (HKI-272) in combination with capecitabine. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Advanced Malignant Solid Tumors
- What is being tested?
- Neratinib and Capecitabine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 2 sitesJapan
- Study dates
- Apr 2010to Mar 2011
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female subjects 20 years and older
- Confirmed pathologic diagnosis of a solid tumor not curable with currently available therapies, for which neratinib plus capecitabine is a reasonable treatment option.
- At least 1 measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria (Please note: ascites, pleural or pericardial effusion, osteoblastic bone metastases, and carcinomatous lymphangitis of the lung will not be considered measurable lesions).
- Subjects with skin lesions that are measurable by computed tomography (CT) scans or magnetic resonance imaging (MRI) as the only site of measurable disease are allowed.
- Recovery from all clinically significant adverse events (AEs) related to prior therapies (excluding alopecia).
- Left ventricular ejection fraction (LVEF) within institutional range of normal as measured by multi-gated acquisition (MUGA) or echocardiogram (ECHO).
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- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (not declining within 2 weeks before signing the informed consent form [ICF]).
- Screening lab values within the following parameters: Absolute neutrophil count (ANC): 1.5×109/L (1500/mm3) Platelet count: 100×109/L (100,000/mm3) Hemoglobin: 9.0 g/dL (90 g/L) Serum creatinine: 01.5×upper limit of normal (ULN) Total bilirubin: 1.5×ULN (<3 ULN if Gilbert's disease) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT): 2.5×ULN (=5×ULN if liver metastases are present)
- For women of childbearing potential, a negative urine or serum pregnancy test result before study entry.
- All subjects who are biologically capable of having children must agree and commit to the use of a reliable method of birth control for the duration of the study and for 28 days after the last dose of investigational product. A subject is biologically capable of having children if he or she is using contraceptives or if his or her sexual partner is sterile or using contraceptives.
Who cannot join
- Prior treatment with anthracyclines with a cumulative dose of doxorubicin >400 mg/m², or of epirubicin >800 mg/m², or the equivalent dose for other anthracyclines or derivatives.
- Major surgery, chemotherapy, radiotherapy, any investigational agents, or other cancer therapy within at least 2 weeks before administration of the first dose of investigational product.
- Bone as the ONLY site of disease .
- Active central nervous system (CNS) metastases, as indicated by clinical symptoms, cerebral edema, and/or progressive growth (subjects with a history of CNS metastases or cord compression are permitted if they have been definitively treated and are off anticonvulsants and steroids for at least 4 weeks before cycle 1 day 1).
- QT (corrected QT (QTc)) interval >0.47seconds or a known history of QTc prolongation or torsades de pointes.
- Presence of clinically significant or uncontrolled cardiac disease, including congestive heart failure (New York Heart Association [NYHA] functional classification of 02), angina requiring treatment, myocardial infarction within the past 12 months, or any clinically significant supraventricular arrhythmia or ventricular arrhythmia requiring treatment or intervention.
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- Pregnant or breastfeeding women.
- Significant chronic or recent acute gastrointestinal disorder with diarrhea as a major symptom (eg, Crohn's disease, malabsorption, or grade 2 or higher diarrhea of any etiology at baseline).
- Inability or unwillingness to swallow tablets (neratinib and capecitabine).
- Subjects with active or uncontrolled renal insufficiency, in whom medication dose adjustments are indicated.
- Subject known to be human immunodeficiency virus (HIV) seropositive and/or have acute or chronic hepatitis B infection (hepatitis B surface antigen [HBsAg] positive) or hepatitis C infection (anti-HCV positive).
- Known history of hypersensitivity to capecitabine or any of it components, including 5-FU.
- Any other cancer within 5 years prior to screening with the exception of contralateral breast carcinoma, adequately treated cervical carcinoma in situ, or adequately treated basal or squamous cell carcinoma of the skin.
- Clinically significant ongoing or recent infection within 2 weeks before administration of the first dose of investigational product.
- Evidence of significant medical illness or abnormal laboratory findings that in the investigator's judgment will substantially increase the risk associated with the subject's participation in and completion of the study, or preclude the evaluation of the subject's response. Examples include, but are not limited to, serious active infection, (ie, requiring intravenous antibiotic or antiviral agent) or uncontrolled major seizure disorder, significant pulmonary disorder (eg, interstitial pneumonitis, pulmonary hypertension), or psychiatric disorder that would interfere with subject safety or informed consent.
Trial locations and contacts
2 sites in 1 country.
About this study
Official title: A Phase 1, Open-Label Study Of Neratinib (HKI-272) In Combination With Capecitabine In Japanese Subject With Solid Tumors
This is an open-label, phase 1 study of a single cohort of neratinib (HKI-272) in combination with capecitabine.
- Conditions
- Advanced Malignant Solid Tumors
- Being tested
- Neratinib, Capecitabine
- Keywords
- Neratinib, Capecitabine, Combination, Solid Tumor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NeratinibDrug
240 mg once daily by mouth.
CapecitabineDrug
1500 mg/m^2 twice daily by mouth.
| Study group | Role | What they receive |
|---|---|---|
| Neratinib + Capecitabine | Experimental | Neratinib + Capecitabine Receives: Drug: Neratinib; Drug: Capecitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Limiting Toxicity (DLT) - Percentage of Participants With DLT Events
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.
Measured: From first dose date to day 21.
Tolerated Dose
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.
Measured: From first dose date to day 21.
Secondary outcomes (5)
Best Overall Response
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.
Measured: From first dose date to progression or last tumor assessment, up to 41 weeks.
Objective Response Rate
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.
Measured: From first dose date to progression or last tumor assessment, up to 41 weeks.
Progression Free Survival
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.
Measured: From first dose date to PD or death, up to 41 weeks.
Area Under the Curve (AUC) of Neratinib in Combination With 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.
Measured: At 1, 2, 4, 6, 8 and 21-24 hours after dose on day 14.
Maximum Plasma Concentration of Neratinib in Combination With 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.
Measured: Measured at 1, 2, 4, 6, 8 and 21-24 hours after dose on day 14.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2010 (estimated)
- Study startApr 2010
- Primary completionMar 2011
- Study completionMar 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Advanced Malignant Solid TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Puma Biotechnology, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Puma, Study director, Biotechnology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01128842
- Sponsor's protocol ID
- 3144A1-1122 / B1891018
- Status last verified
- Dec 2018
- First submitted
- 20 May 2010
- Last updated
- 19 Dec 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-Label Study Of Neratinib (HKI-272) In Combination With Capecitabine In Japanese Subject With Solid Tumors
- ClinicalTrials.gov ID
- NCT01128842
- Acronym / sponsor ID
- 3144A1-1122 / B1891018
- Conditions
- Advanced Malignant Solid Tumors
- Keywords
- Neratinib, Capecitabine, Combination, Solid Tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Puma Biotechnology, Inc.Industry (pharma, biotech, devices)
- Study start
- Apr 2010 (actual)
- Primary completion
- Mar 2011 (actual)
- Study completion
- Mar 2011 (actual)
- First posted
- 24 May 2010 (estimated)
- Results
- Posted 19 Dec 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label, phase 1 study of a single cohort of neratinib (HKI-272) in combination with capecitabine.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Neratinib + Capecitabine | Experimental | Drug: Neratinib, Drug: CapecitabineNeratinib + Capecitabine |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Male and female subjects 20 years and older
- Confirmed pathologic diagnosis of a solid tumor not curable with currently available therapies, for which neratinib plus capecitabine is a reasonable treatment option.
- At least 1 measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria (Please note: ascites, pleural or pericardial effusion, osteoblastic bone metastases, and carcinomatous lymphangitis of the lung will not be considered measurable lesions).
- Subjects with skin lesions that are measurable by computed tomography (CT) scans or magnetic resonance imaging (MRI) as the only site of measurable disease are allowed.
- Recovery from all clinically significant adverse events (AEs) related to prior therapies (excluding alopecia).
Key exclusion criteria (15 listed)
- Prior treatment with anthracyclines with a cumulative dose of doxorubicin >400 mg/m², or of epirubicin >800 mg/m², or the equivalent dose for other anthracyclines or derivatives.
- Major surgery, chemotherapy, radiotherapy, any investigational agents, or other cancer therapy within at least 2 weeks before administration of the first dose of investigational product.
- Bone as the ONLY site of disease .
- Active central nervous system (CNS) metastases, as indicated by clinical symptoms, cerebral edema, and/or progressive growth (subjects with a history of CNS metastases or cord compression are permitted if they have been definitively treated and are off anticonvulsants and steroids for at least 4 weeks before cycle 1 day 1).
- QT (corrected QT (QTc)) interval >0.47seconds or a known history of QTc prolongation or torsades de pointes.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Neratinib240 mg once daily by mouth. | Drug | Neratinib + Capecitabine |
| Capecitabine1500 mg/m^2 twice daily by mouth. | Drug | Neratinib + Capecitabine |
Primary outcome
Dose Limiting Toxicity (DLT) - Percentage of Participants With DLT Events
Time frame: From first dose date to day 21.
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.
Tolerated Dose
Time frame: From first dose date to day 21.
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.
5 secondary outcomes
Best Overall Response
Time frame: From first dose date to progression or last tumor assessment, up to 41 weeks.
Objective Response Rate
Time frame: From first dose date to progression or last tumor assessment, up to 41 weeks.
Progression Free Survival
Time frame: From first dose date to PD or death, up to 41 weeks.
Area Under the Curve (AUC) of Neratinib in Combination With Capecitabine
Time frame: At 1, 2, 4, 6, 8 and 21-24 hours after dose on day 14.
Maximum Plasma Concentration of Neratinib in Combination With Capecitabine
Time frame: Measured at 1, 2, 4, 6, 8 and 21-24 hours after dose on day 14.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Puma study director
Biotechnology
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Neratinib and Capecitabine in people with Advanced Malignant Solid Tumors, run by Puma Biotechnology, Inc. at 2 sites in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Dec 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose Limiting Toxicity (DLT) - Percentage of Participants With DLT Events (time frame: From first dose date to day 21.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2018.