Advanced Malignant Solid TumorsPhase 1NCT00958724
Study Evaluating Neratinib In Combination With Vinorelbine In Subjects With Advanced Or Metastatic Solid Tumors
A Phase 1 study testing Neratinib and Vinorelbine in people with Advanced Malignant Solid Tumors, run by Puma Biotechnology, Inc. at 2 sites in Japan.
Trial summary
The purposes of this study are to evaluate the safety and tolerability of neratinib in combination with vinorelbine at the maximum tolerated dose (MTD) determined in a previous study, or to determine a lower MTD of the two drugs, as well as to obtain preliminary information on whether the combination of the two drugs… 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 Vinorelbine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 2 sitesJapan
- Study dates
- Jul 2009to Apr 2010
- 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
- Confirmed pathologic diagnosis of a solid tumor that is not curable with available therapies for which neratinib plus vinorelbine is a reasonable treatment option.
- At least 1 measurable lesion as defined by Response Evaluation Criteria in Solid Tumors.
- Eastern Cooperative Oncology Group performance status of 0 to 2 (not declining within 2 weeks before signing the informed consent form).
- Recovery from all clinically significant AEs related to prior therapies (excluding alopecia).
- Left ventricular ejection fraction within the study site's limits of normal.
- Screening laboratory values within the following parameters:
Show all 14Show fewer
- Absolute neutrophil count: 1.5 × 109/L
- Platelet count: 100 × 109/L
- Hemoglobin: 9.0 g/dL
- Serum creatinine: 1.5 × upper limit of normal
- Total bilirubin: 1.5 × ULN
- Aspartate aminotransferase and alanine aminotransferase: 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 female and male 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 test article. 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 of >400 mg/m^2, or of epirubicin >800 mg/m^2, or the equivalent dose for other anthracyclines or derivatives.
- Major surgery, chemotherapy, radical (curative intent) radiotherapy, investigational agents, or other cancer therapy within at least 2 weeks before treatment day 1.
- Bone as the only site of disease.
- Active central nervous system metastases, as indicated by clinical symptoms, cerebral edema, and/or progressive growth. (Subjects with a history of CNS metastases or cord compression are allowable if they have been definitively treated and are off anticonvulsants and steroids for at least 4 weeks before cycle 1 day 1) .
- QT (QTc) interval > 0.47 s 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 functional classification of =2), angina requiring treatment, myocardial infarction within the past 12 months, or any clinically significant supraventricular arrhythmia or ventricular arrhythmia requiring treatment or intervention.
Show all 14Show fewer
- Pregnant or breastfeeding women. Significant chronic or recent acute gastrointestinal disorder with diarrhea as a major symptom (eg, Crohn disease, malabsorption, or grade 2 diarrhea of any etiology at baseline).
- Inability or unwillingness to swallow tablets (neratinib).
- Preexisting grade 2 or greater motor or sensory neuropathy.
- Subject known to be human immunodeficiency virus seropositive and/or have acute or chronic hepatitis B infection (hepatitis B surface antigen [HBsAg] positive) or hepatitis C infection (anti-HCV positive).
- History of known hypersensitivity to vinorelbine and any of its components.
- 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 treatment day 1.
- Evidence of significant medical illness or abnormal laboratory finding that would, in the investigator's judgment, make the subject inappropriate for this study. Examples include, but are not limited to, serious active infection (ie, requiring intravenous antibiotic or antiviral agent) or uncontrolled major seizure.
Trial locations and contacts
2 sites in 1 country.
Japan2 sites
Shizuoka Cancer Center
Shizuoka, 411-8777
The Cancer Institute Hospital of Japanese Foundation for Cancer Research
Tokyo, 135-8550
About this study
Official title: A Phase 1 Study Of Neratinib (HKI-272) In Combination With Vinorelbine In Japanese Subjects With Advanced Or Metastatic Solid Tumors
The purposes of this study are to evaluate the safety and tolerability of neratinib in combination with vinorelbine at the maximum tolerated dose (MTD) determined in a previous study, or to determine a lower MTD of the two drugs, as well as to obtain preliminary information on whether the combination of the two drugs has any effect on solid tumors in Japanese patients.
- Conditions
- Advanced Malignant Solid Tumors
- Being tested
- Neratinib, Vinorelbine
- Keywords
- HKI-272, Vinorelbine, Combination, Solid Tumor, Neratinib, Nerlynx, PB-272
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NeratinibDrug
Also called HKI-272, Nerlynx
VinorelbineDrug
| Study group | Role | What they receive |
|---|---|---|
| Neratinib and Vinorelbine | Experimental | Neratinib: 240 mg administered daily by mouth continuously, Vinorelbine: 25 mg/m^2 administered IV on Day 1 and 8 of 21 day cycle Receives: Drug: Neratinib; Drug: Vinorelbine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Limiting Toxicity (DLT)
Number of participants experiencing DLT of neratinib in combination with vinorelbine in Japanese patients.
Measured: From first dose date to 21st day
Secondary outcomes (6)
Best Overall Response
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.
Measured: From first dose date to progression or last tumor assessment, up to 40 weeks.
Duration of Objective 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.
Measured: From first response date to PD/death, up to 40 weeks.
Objective Response Rate (ORR)
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.
Measured: From first dose date to progression or last tumor assessment, up to 40 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 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.
Measured: From first dose to last evaluation, up to 40 weeks.
Area Under the Curve (AUC) Tau
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.
Measured: Predose, and hour 1, 2, 4, 6, 8 and 24 on day 8.
Terminal-phase Elimination Half-life
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.
Measured: Predose, and hour 1, 2, 4, 6, 8 and 24 on day 8.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2009 (estimated)
- Study startJul 2009
- Primary completionApr 2010
- Study completionApr 2010
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
- 6 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
- NCT00958724
- Sponsor's protocol ID
- 3144A2-1118 / B1891002
- Status last verified
- Apr 2018
- First submitted
- 5 Aug 2009
- Last updated
- 28 Jun 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 28 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study Of Neratinib (HKI-272) In Combination With Vinorelbine In Japanese Subjects With Advanced Or Metastatic Solid Tumors
- ClinicalTrials.gov ID
- NCT00958724
- Acronym / sponsor ID
- 3144A2-1118 / B1891002
- Conditions
- Advanced Malignant Solid Tumors
- Keywords
- HKI-272, Vinorelbine, Combination, Solid Tumor, Neratinib, Nerlynx, PB-272
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Puma Biotechnology, Inc.Industry (pharma, biotech, devices)
- Study start
- Jul 2009 (actual)
- Primary completion
- Apr 2010 (actual)
- Study completion
- Apr 2010 (actual)
- First posted
- 13 Aug 2009 (estimated)
- Results
- Posted 26 Feb 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purposes of this study are to evaluate the safety and tolerability of neratinib in combination with vinorelbine at the maximum tolerated dose (MTD) determined in a previous study, or to determine a lower MTD of the two drugs, as well as to obtain preliminary information on whether the combination of the two drugs has any effect on solid tumors in Japanese patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Neratinib and Vinorelbine | Experimental | Drug: Neratinib, Drug: VinorelbineNeratinib: 240 mg administered daily by mouth continuously, Vinorelbine: 25 mg/m^2 administered IV on Day 1 and 8 of 21 day cycle |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Confirmed pathologic diagnosis of a solid tumor that is not curable with available therapies for which neratinib plus vinorelbine is a reasonable treatment option.
- At least 1 measurable lesion as defined by Response Evaluation Criteria in Solid Tumors.
- Eastern Cooperative Oncology Group performance status of 0 to 2 (not declining within 2 weeks before signing the informed consent form).
- Recovery from all clinically significant AEs related to prior therapies (excluding alopecia).
- Left ventricular ejection fraction within the study site's limits of normal.
Key exclusion criteria (14 listed)
- Prior treatment with anthracyclines with a cumulative dose of doxorubicin of >400 mg/m^2, or of epirubicin >800 mg/m^2, or the equivalent dose for other anthracyclines or derivatives.
- Major surgery, chemotherapy, radical (curative intent) radiotherapy, investigational agents, or other cancer therapy within at least 2 weeks before treatment day 1.
- Bone as the only site of disease.
- Active central nervous system metastases, as indicated by clinical symptoms, cerebral edema, and/or progressive growth. (Subjects with a history of CNS metastases or cord compression are allowable if they have been definitively treated and are off anticonvulsants and steroids for at least 4 weeks before cycle 1 day 1) .
- QT (QTc) interval > 0.47 s 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 |
|---|---|---|
| NeratinibAlso: HKI-272, Nerlynx | Drug | Neratinib and Vinorelbine |
| Vinorelbine | Drug | Neratinib and Vinorelbine |
Primary outcome
Dose Limiting Toxicity (DLT)
Time frame: From first dose date to 21st day
Number of participants experiencing DLT of neratinib in combination with vinorelbine in Japanese patients.
6 secondary outcomes
Best Overall Response
Time frame: From first dose date to progression or last tumor assessment, up to 40 weeks.
Duration of Objective Response
Time frame: From first response date to PD/death, up to 40 weeks.
Objective Response Rate (ORR)
Time frame: From first dose date to progression or last tumor assessment, up to 40 weeks.
Progression Free Survival
Time frame: From first dose to last evaluation, up to 40 weeks.
Area Under the Curve (AUC) Tau
Time frame: Predose, and hour 1, 2, 4, 6, 8 and 24 on day 8.
Terminal-phase Elimination Half-life
Time frame: Predose, and hour 1, 2, 4, 6, 8 and 24 on day 8.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Advanced Malignant Solid Tumors
Active, not recruitingPhase 1/2
A Beta-only IL-2 ImmunoTherapY Study
Advanced Solid Tumor, Unresectable Solid Tumor
RecruitingPhase 1
SW-682 in Advanced Solid Tumors
Advanced Solid Tumor, Mesothelioma, Malignant
RecruitingPhase 1
PAS-004 in Patients With Advanced Solid Tumors
RAS Mutation, NF1 Mutation
RecruitingPhase 2
Targeted Therapy Directed by Genetic Testing in Treating Patients With Locally Advanced or Advanced Solid Tumors, The ComboMATCH Screening Trial
Advanced Malignant Solid Neoplasm, Anatomic Stage III Breast Cancer AJCC v8
RecruitingPhase 1
Metarrestin (ML-246) in Subjects With Metastatic Solid Tumors
Advanced Solid Tumors, Metastatic Pancreatic Cancer
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 Vinorelbine 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 14 inclusion and 14 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 28 Jun 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 26 Feb 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) (time frame: From first dose date to 21st day). 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 28 Jun 2018.