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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Neratinib | Drug |
|
| |
| Vinorelbine |
| Measure | Description | Time Frame |
|---|---|---|
| Dose Limiting Toxicity (DLT) | Number of participants experiencing DLT of neratinib in combination with vinorelbine in Japanese patients. | From first dose date to 21st day |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | From first dose date to progression or last tumor assessment, up to 40 weeks. |
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Inclusion Criteria:
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:
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.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Puma | Biotechnology | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Shizuoka Cancer Center | Shizuoka | 411-8777 | Japan | |||
| The Cancer Institute Hospital of Japanese Foundation for Cancer Research |
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| ID | Title | Description |
|---|---|---|
| FG000 | Nera 240 + Vino 25 | Neratinib 240 mg + Vinorelbine 25 mg/m^2 |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Nera 240 + Vino 25 | Neratinib 240 mg + Vinorelbine 25 mg/m^2 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Dose Limiting Toxicity (DLT) | Number of participants experiencing DLT of neratinib in combination with vinorelbine in Japanese patients. | Safety population | Posted | Number | participants | From first dose date to 21st day |
|
|
From first dose through 28 days after last dose, up to 40 weeks.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Nera 240 + Vino 25 | Neratinib 240 mg + Vinorelbine 25 mg/m^2 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Peritoneal abscess | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (17.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Director, Clinical Operations | Puma Biotechnology, Inc. | +1 (424) 248-6500 | clinicaltrials@pumabiotechnology.com |
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| ID | Term |
|---|---|
| C487932 | neratinib |
| D000077235 | Vinorelbine |
| ID | Term |
|---|---|
| D014748 | Vinca Alkaloids |
| D046948 | Secologanin Tryptamine Alkaloids |
| D026121 | Indole Alkaloids |
| D000470 | Alkaloids |
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| Drug |
|
| 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. | 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. | 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. | 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. | 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. | Predose, and hour 1, 2, 4, 6, 8 and 24 on day 8. |
| Tokyo |
| 135-8550 |
| Japan |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
|
| Secondary | 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. | 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. | Posted | Count of Participants | Participants | From first dose date to progression or last tumor assessment, up to 40 weeks. |
|
|
|
| Secondary | 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. | Subjects who had a partial or complete response | Posted | Median | 95% Confidence Interval | weeks | From first response date to PD/death, up to 40 weeks. |
|
|
|
| Secondary | 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. | Safety population | Posted | Number | 95% Confidence Interval | percentage of participants | From first dose date to progression or last tumor assessment, up to 40 weeks. |
|
|
|
| Secondary | 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. | 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. | Posted | Median | 95% Confidence Interval | weeks | From first dose to last evaluation, up to 40 weeks. |
|
|
|
| Secondary | 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. | 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. | Posted | Mean | Standard Deviation | ng*hr/mL | Predose, and hour 1, 2, 4, 6, 8 and 24 on day 8. |
|
|
|
| Secondary | 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. | 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. | Posted | Mean | Standard Deviation | hr | Predose, and hour 1, 2, 4, 6, 8 and 24 on day 8. |
|
|
|
| 1 |
| 6 |
| 6 |
| 6 |
| Leukopenia | Blood and lymphatic system disorders | MedDRA (17.0) | Systematic Assessment |
|
| Lymphopenia | Blood and lymphatic system disorders | MedDRA (17.0) | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (17.0) | Systematic Assessment |
|
| Left ventricular dysfunction | Cardiac disorders | MedDRA (17.0) | Systematic Assessment |
|
| Keratitis | Eye disorders | MedDRA (17.0) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
|
| Enterocolitis | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
|
| Face oedema | General disorders | MedDRA (17.0) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (17.0) | Systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA (17.0) | Systematic Assessment |
|
| Non-cardiac chest pain | General disorders | MedDRA (17.0) | Systematic Assessment |
|
| Performance status decreased | General disorders | MedDRA (17.0) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (17.0) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
|
| Proctitis infectious | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
|
| Lumbar vertebral fracture | Injury, poisoning and procedural complications | MedDRA (17.0) | Systematic Assessment |
|
| Rib fracture | Injury, poisoning and procedural complications | MedDRA (17.0) | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA (17.0) | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA (17.0) | Systematic Assessment |
|
| Blood chloride decreased | Investigations | MedDRA (17.0) | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA (17.0) | Systematic Assessment |
|
| Blood lactate dehydrogenase increased | Investigations | MedDRA (17.0) | Systematic Assessment |
|
| Blood sodium decreased | Investigations | MedDRA (17.0) | Systematic Assessment |
|
| Eastern Cooperative Oncology Group performance status worsened | Investigations | MedDRA (17.0) | Systematic Assessment |
|
| Electrocardiogram QT prolonged | Investigations | MedDRA (17.0) | Systematic Assessment |
|
| Haematocrit decreased | Investigations | MedDRA (17.0) | Systematic Assessment |
|
| Haemoglobin decreased | Investigations | MedDRA (17.0) | Systematic Assessment |
|
| Monocyte count decreased | Investigations | MedDRA (17.0) | Systematic Assessment |
|
| Protein urine | Investigations | MedDRA (17.0) | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA (17.0) | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (17.0) | Systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA (17.0) | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (17.0) | Systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA (17.0) | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
|
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (17.0) | Systematic Assessment |
|
| Aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment |
|
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment |
|
| Laryngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (17.0) | Systematic Assessment |
|
| Decubitus ulcer | Skin and subcutaneous tissue disorders | MedDRA (17.0) | Systematic Assessment |
|
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA (17.0) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (17.0) | Systematic Assessment |
|
| Skin fissures | Skin and subcutaneous tissue disorders | MedDRA (17.0) | Systematic Assessment |
|
| Vasculitis | Vascular disorders | MedDRA (17.0) | Systematic Assessment |
|
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| D006571 |
| Heterocyclic Compounds |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D054836 | Indolizidines |
| D007212 | Indolizines |
| Title | Measurements |
|---|---|
|