Breast Cancer
Conditions
Keywords
ErbB-2 positive advanced breast cancer, HKI-272, Neratinib, Nerlynx, HER2, PB-272, metastatic breast cancer
Brief summary
This study is investigating the effects of an experimental drug (neratinib) in combination with paclitaxel versus trastuzumab in combination with paclitaxel for the treatment of women who have not received previous treatment for erbB-2-positive locally recurrent or metastatic breast cancer. The study will compare the effectiveness of each regimen in shrinking tumors and extending the lives of women with erbB-2 (HER2) positive breast cancer. The study will also compare the safety of the two regimens and as well as the quality of life of subjects receiving either regimen.
Interventions
DRUGNeratinib
Neratinib - 240 mg orally daily, administered once daily. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent.
DRUGTrastuzumab
Trastuzumab - 4 mg/kg IV initial loading dose followed by subsequent once weekly doses of 2mg/kg IV. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent.
DRUGPaclitaxel
Paclitaxel - 80 mg/m² IV administered on days 1, 8, and 15 of a 28-day cycle. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent.
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
* ErbB-2 positive locally recurrent or metastatic breast cancer * Eastern Cooperative Oncology Group (ECOG) 0-2 * Measurable disease * Availability of tumor tissue for HER2 status confirmation
Exclusion criteria
* Prior systemic anti-cancer therapy other than endocrine therapy for locally recurrent or metastatic disease * Prior erbB-2 inhibitor other than trastuzumab or lapatinib in the neoadjuvant or adjuvant setting * Progression/recurrence within 12 months after completion of adjuvant or neoadjuvant therapy * History of heart disease * History of gastrointestinal disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival | From randomization to disease progression or death, assessed up to 5.3 years | Defined as the interval from the date of randomization until the first date on which recurrence or progression, or death due to any cause, is documented, censored at the last assessable evaluation or at the initiation of new anticancer therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | From randomization to disease progression or last tumor assessment, assessed up to 5.3 years | Defined as the percentage of subjects who achieved confirmed tumor response (complete or partial response) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.0: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; and Non-Progressive Disease for non-target lesions, and no new lesions. |
| Duration of Response | From first response to first PD or death, assessed up to 5.3 years after first subject randomized | Measured from the time at which measurement criteria were first met for CR or PR (whichever status was recorded first), until the date of first recurrence, disease progression (PD), or death was objectively documented, taking as a reference for PD the smallest measurements recorded since enrollment, per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.0: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; and Non-PD for non-target lesions, and no new lesions. |
| Clinical Benefit Rate | From randomization to disease progression or death, assessed up to 5.3 years | Defined as the proportion of patients who achieved overall tumor response (CR or PR) or SD for at least 24 weeks per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.0: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; and Non-PD for non-target lesions, and no new lesions; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. |
| Symptomatic or Progressive Central Nervous System (CNS) Lesions | From randomization to disease progression PD or last tumor assessment, assessed up to 5.3 years | Defined as the time interval from the date of randomization until the first date of CNS symptoms, the imaging examination shows CNS progression or is censored at the last assessable evaluation on study or prior to new anti-cancer therapy, if applicable. If median time to Symptomatic or Progressive CNS Lesions is not estimable, cumulative incidence will be reported instead. |
Countries
Australia, Belarus, Belgium, Bulgaria, Canada, China, Croatia, Denmark, France, Germany, Hong Kong, Hungary, India, Israel, Italy, Japan, Latvia, Lithuania, Malaysia, Malta, Poland, Portugal, Romania, Serbia, Singapore, South Africa, South Korea, Spain, Switzerland, Taiwan, The Bahamas, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Neratinib + Paclitaxel Neratinib + Paclitaxel
Neratinib: Neratinib - 240 mg orally daily, administered once daily. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent.
Paclitaxel: Paclitaxel - 80 mg/m2 IV administered on days 1, 8, and 15 of a 28-day cycle. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent. | 242 |
| Trastuzumab + Paclitaxel Trastuzumab + Paclitaxel
Trastuzumab: Trastuzumab - 4 mg/kg IV initial loading dose followed by subsequent once weekly doses of 2 mg/kg IV. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent.
Paclitaxel: Paclitaxel - 80 mg/m2 IV administered on days 1, 8, and 15 of a 28-day cycle. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent. | 237 |
| Total | 479 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | By Sponsor due to Protocol Amendment | 92 | 105 |
| Overall Study | Death | 75 | 70 |
| Overall Study | Lost to Follow-up | 10 | 5 |
| Overall Study | Withdrawal by Subject | 38 | 27 |
Baseline characteristics
| Characteristic | Neratinib + Paclitaxel | Trastuzumab + Paclitaxel | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 43 Participants | 44 Participants | 87 Participants |
| Age, Categorical Between 18 and 65 years | 199 Participants | 193 Participants | 392 Participants |
| Age, Continuous | 54.0 years STANDARD_DEVIATION 11.6 | 54.3 years STANDARD_DEVIATION 11 | 54.1 years STANDARD_DEVIATION 11.3 |
| Sex: Female, Male Female | 242 Participants | 237 Participants | 479 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 | 239 / 240 | 230 / 234 |
| serious Total, serious adverse events | 67 / 240 | 56 / 234 |
Outcome results
Primary
Progression-Free Survival
Defined as the interval from the date of randomization until the first date on which recurrence or progression, or death due to any cause, is documented, censored at the last assessable evaluation or at the initiation of new anticancer therapy.
Time frame: From randomization to disease progression or death, assessed up to 5.3 years
Population: all randomized patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Neratinib + Paclitaxel | Progression-Free Survival | 12.9 months |
| Trastuzumab + Paclitaxel | Progression-Free Survival | 12.9 months |
p-value: 0.893495% CI: [0.813, 1.269]Log Rank
Secondary
Clinical Benefit Rate
Defined as the proportion of patients who achieved overall tumor response (CR or PR) or SD for at least 24 weeks per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.0: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; and Non-PD for non-target lesions, and no new lesions; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Time frame: From randomization to disease progression or death, assessed up to 5.3 years
Population: all randomized patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Neratinib + Paclitaxel | Clinical Benefit Rate | 88.4 percentage of participants |
| Trastuzumab + Paclitaxel | Clinical Benefit Rate | 85.2 percentage of participants |
p-value: 0.23695% CI: [-0.093, 0.029]Mantel Haenszel
Secondary
Duration of Response
Measured from the time at which measurement criteria were first met for CR or PR (whichever status was recorded first), until the date of first recurrence, disease progression (PD), or death was objectively documented, taking as a reference for PD the smallest measurements recorded since enrollment, per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.0: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; and Non-PD for non-target lesions, and no new lesions.
Time frame: From first response to first PD or death, assessed up to 5.3 years after first subject randomized
Population: patients who responded
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Neratinib + Paclitaxel | Duration of Response | 13.1 months |
| Trastuzumab + Paclitaxel | Duration of Response | 12.9 months |
p-value: 0.843195% CI: [0.752, 1.262]Log Rank
Secondary
Objective Response Rate
Defined as the percentage of subjects who achieved confirmed tumor response (complete or partial response) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.0: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; and Non-Progressive Disease for non-target lesions, and no new lesions.
Time frame: From randomization to disease progression or last tumor assessment, assessed up to 5.3 years
Population: all randomized patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Neratinib + Paclitaxel | Objective Response Rate | 74.8 percentage of participants |
| Trastuzumab + Paclitaxel | Objective Response Rate | 77.6 percentage of participants |
p-value: 0.521995% CI: [-0.048, 0.105]Mantel Haenszel
Secondary
Symptomatic or Progressive Central Nervous System (CNS) Lesions
Defined as the time interval from the date of randomization until the first date of CNS symptoms, the imaging examination shows CNS progression or is censored at the last assessable evaluation on study or prior to new anti-cancer therapy, if applicable. If median time to Symptomatic or Progressive CNS Lesions is not estimable, cumulative incidence will be reported instead.
Time frame: From randomization to disease progression PD or last tumor assessment, assessed up to 5.3 years
Population: all randomized patients
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Neratinib + Paclitaxel | Symptomatic or Progressive Central Nervous System (CNS) Lesions | 20 Participants |
| Trastuzumab + Paclitaxel | Symptomatic or Progressive Central Nervous System (CNS) Lesions | 41 Participants |
p-value: 0.003695% CI: [0.259, 0.78]Log Rank