Breast Neoplasms, Neoplasms
Conditions
Keywords
phase 2, HER2+ breast cancer, monotherapy neratinib, HKI-272, Neratinib, Nerlynx, PB-272
Brief summary
The purpose of this study is to learn whether neratinib is safe and effective in treating women with advanced human epidermal growth factor receptor 2 (HER2) positive breast cancer.
Detailed description
Arm A: HER2 gene amplification and disease progression following at least 6 weeks of standard doses of Herceptin; Arm B: HER2 gene amplification and no prior Herceptin or HER2-targeted treatment.
Interventions
DRUGneratinib
Sponsors
Puma Biotechnology, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Pathologic diagnosis of breast cancer and current stage IIIB, IIIC, or IV * Progression following at least 6 weeks of standard doses of Herceptin (Arm A only) * Over-expression of HER2 * Tumor tissue available and adequate for analysis at screening * At least one measurable lesion
Exclusion criteria
* Prior treatment with Herceptin (Arm B only) * More than 4 prior cytotoxic chemotherapy regimens * Subjects with bone or skin as the only site of measurable disease * Inadequate cardiac function * Major surgery, chemotherapy, radiotherapy, investigational agents or other cancer therapy within 1 week of treatment day 1 * Active central nervous system metastases * Pregnant or breastfeeding women * Inability to swallow the HKI-272 capsules
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 16-week Progression Free Survival | From first dose to 16 weeks | 16 week progression-free survival (PFS) rate of neratinib in women with human epidermal growth factor receptor 2 (HER2) positive breast cancer, either with prior trastuzumab or no prior trastuzumab therapy, evaluated by independent assessment of tumor scans collected at baseline and then every 8 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | From first dose date to progression or last tumor assessment, up to 46 months | Percentage of participants with Partial Response (PR) or Complete Response (CR) by independent assessment of tumor per 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. |
| Clinical Benefit Rate | From first dose date to progression or last tumor assessment, up to 46 months | Percentage of participants who experienced Complete Response (CR), Partial Response (PR), or Stable Disease (SD) ≥ 24 weeks by independent assessment 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. |
| Duration of Response | From start date of response to first PD/death, up to 46 months | Number of weeks between Complete Response (CR) or Partial Response (PR) and the first date of disease progression (PD) or death 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 |
Countries
Belgium, China, France, India, Mexico, Russia, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Neratinib 240, Prior Trastuzumab Neratinib: 80mg capsules and 40mg coated tablets taken orally in prescribed dose of 240mg daily, as long as tolerated and disease does not worsen in participants with prior trastuzumab treatment. | 66 |
| Neratinib 240, No Prior Trastuzumab Neratinib: 80mg capsules and 40mg coated tablets taken orally in prescribed dose of 240mg daily, as long as tolerated and disease does not worsen in participants with no prior trastuzumab treatment. | 70 |
| Total | 136 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 6 |
| Overall Study | Disease Progression | 55 | 52 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Not Recorded | 0 | 1 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Symptomatic Deterioration | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Neratinib 240, No Prior Trastuzumab | Total | Neratinib 240, Prior Trastuzumab |
|---|---|---|---|
| Age, Continuous | 49.64 years STANDARD_DEVIATION 9.92 | 50.60 years STANDARD_DEVIATION 10.3 | 51.62 years STANDARD_DEVIATION 10.67 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 52 Participants | 58 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) White | 15 Participants | 70 Participants | 55 Participants |
| Sex: Female, Male Female | 70 Participants | 136 Participants | 66 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 66 / 66 | 70 / 70 |
| serious Total, serious adverse events | 19 / 66 | 17 / 70 |
Outcome results
Primary
16-week Progression Free Survival
16 week progression-free survival (PFS) rate of neratinib in women with human epidermal growth factor receptor 2 (HER2) positive breast cancer, either with prior trastuzumab or no prior trastuzumab therapy, evaluated by independent assessment of tumor scans collected at baseline and then every 8 weeks.
Time frame: From first dose to 16 weeks
Population: Intent to Treat Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Neratinib 240, Prior Trastuzumab | 16-week Progression Free Survival | 58.2 percentage of participants |
| Neratinib 240, No Prior Trastuzumab | 16-week Progression Free Survival | 77.8 percentage of participants |
Secondary
Clinical Benefit Rate
Percentage of participants who experienced Complete Response (CR), Partial Response (PR), or Stable Disease (SD) ≥ 24 weeks by independent assessment 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.
Time frame: From first dose date to progression or last tumor assessment, up to 46 months
Population: Intent to Treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Neratinib 240, Prior Trastuzumab | Clinical Benefit Rate | 31.8 percentage of participants |
| Neratinib 240, No Prior Trastuzumab | Clinical Benefit Rate | 62.9 percentage of participants |
Secondary
Duration of Response
Number of weeks between Complete Response (CR) or Partial Response (PR) and the first date of disease progression (PD) or death 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
Time frame: From start date of response to first PD/death, up to 46 months
Population: Subjects in Intent to Treat population with CR or PR
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Neratinib 240, Prior Trastuzumab | Duration of Response | 40.3 weeks |
| Neratinib 240, No Prior Trastuzumab | Duration of Response | 60.0 weeks |
Secondary
Objective Response Rate
Percentage of participants with Partial Response (PR) or Complete Response (CR) by independent assessment of tumor per 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.
Time frame: From first dose date to progression or last tumor assessment, up to 46 months
Population: Intent to Treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Neratinib 240, Prior Trastuzumab | Objective Response Rate | 24.2 percentage of participants |
| Neratinib 240, No Prior Trastuzumab | Objective Response Rate | 52.9 percentage of participants |