Breast Cancer Nos Metastatic Recurrent
Conditions
Keywords
NK105, Paclitaxel, Breast cancer, Micelle
Brief summary
To verify the non-inferiority of NK105, a paclitaxel-incorporating micellar nanoparticle, to paclitaxel in terms of the progression-free survival in patients with metastatic or recurrent breast cancer.
Detailed description
This study is a randomized, open-label, multi-national phase III study.
Interventions
DRUGNK105
IV, Weekly
DRUGPaclitaxel
IV, Weekly
Sponsors
Nippon Kayaku Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
20 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
* Written informed consent of the patient signed by herself. * Histologically confirmed metastatic or recurrent adenocarcinoma of the breast. * Aged 20 to 74 at the time of informed consent.
Exclusion criteria
* Prior systemic chemotherapy with taxane anticancer drugs for metastatic or recurrent breast cancer.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | Baseline, every 6 weeks of study treatment period, and end of study, | PFS is defined as the period from the day of randomization until the first observation of lesion progression or death from any cause. Disease progression is defined as PD according to RECIST Ver. 1.1. Assessment period was from the day of randomisation until the first observation of lesion progression or death |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Baseline, every 6 weeks of study treatment period, and end of study. | OS is defined as the period from the day of randomization until the day of death from any cause. Assessment period was from the day of randomisation until the first observation of lesion progression or death |
| Overall Response Rate | Baseline, every 6 weeks of study treatment period, and end of study. | ORR is the proportion of patients who are assessed as complete response or partial response as the best overall response among evaluable patients, according to RECIST Ver.1.1. Assessment period was from the day of randomisation until the first observation of lesion progression or death |
Countries
Japan
Participant flow
Recruitment details
This study was conducted from September 2012 to January 2016 in three asian countries (Japan, Korea, Taiwan).
Participants by arm
| Arm | Count |
|---|---|
| NK105 received NK105 (65 mg/m\^2) on days 1, 8 and 15 of a 28-day cycle | 214 |
| Paclitaxel received Paclitaxel (80 mg/m\^2) on days 1, 8 and 15 of a 28-day cycle | 213 |
| Total | 427 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | > 28 days since last dose of study drug | 6 | 3 |
| Overall Study | Adverse Event | 7 | 20 |
| Overall Study | Clinical Progression | 6 | 6 |
| Overall Study | Death | 1 | 3 |
| Overall Study | Other | 8 | 9 |
| Overall Study | Physician Decision | 3 | 9 |
| Overall Study | Progression Disease | 160 | 131 |
| Overall Study | Protocol Violation | 6 | 7 |
| Overall Study | Withdrawal by Subject | 19 | 27 |
Baseline characteristics
| Characteristic | NK105 | Paclitaxel | Total |
|---|---|---|---|
| Age, Continuous | 55.1 years STANDARD_DEVIATION 10.3 | 55.0 years STANDARD_DEVIATION 10.7 | 55.1 years STANDARD_DEVIATION 10.5 |
| Region of Enrollment Japan | 136 participants | 143 participants | 279 participants |
| Region of Enrollment South Korea | 51 participants | 42 participants | 93 participants |
| Region of Enrollment Taiwan | 27 participants | 28 participants | 55 participants |
| Sex: Female, Male Female | 214 Participants | 213 Participants | 427 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 | 3 / 214 | 4 / 213 |
| other Total, other adverse events | 210 / 214 | 211 / 211 |
| serious Total, serious adverse events | 34 / 214 | 27 / 213 |
Outcome results
Primary
Progression Free Survival
PFS is defined as the period from the day of randomization until the first observation of lesion progression or death from any cause. Disease progression is defined as PD according to RECIST Ver. 1.1. Assessment period was from the day of randomisation until the first observation of lesion progression or death
Time frame: Baseline, every 6 weeks of study treatment period, and end of study,
Population: All randomized patients who received study drug at least once and who had no major violations of the eligiblity criteria
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NK105 | Progression Free Survival | 8.4 months |
| Paclitaxel | Progression Free Survival | 8.5 months |
Comparison: Based on the results of previous studies, the expected median PFS was 5.5 months for PTX and 6.35 months for NK105. Assuming a randomization period of 18 months, a follow-up period of 12 months, a one-sided significance level of 2.5%, a power of 85% and the non-inferiority margin of 1.215, the number of patients was estimated to 172 pts per group, a total of 344 patients. Considering an expected withdrawal/dropout rate of approximately 20%, the target sample size was set at 414.95% CI: [0.989, 1.592]
Secondary
Overall Response Rate
ORR is the proportion of patients who are assessed as complete response or partial response as the best overall response among evaluable patients, according to RECIST Ver.1.1. Assessment period was from the day of randomisation until the first observation of lesion progression or death
Time frame: Baseline, every 6 weeks of study treatment period, and end of study.
Population: All randomized patients who received study drug at least once and who had no major violations of the eligiblity criteria
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NK105 | Overall Response Rate | 31.6 percentage of participants |
| Paclitaxel | Overall Response Rate | 39.0 percentage of participants |
95% CI: [-17.4, 2.7]
Secondary
Overall Survival
OS is defined as the period from the day of randomization until the day of death from any cause. Assessment period was from the day of randomisation until the first observation of lesion progression or death
Time frame: Baseline, every 6 weeks of study treatment period, and end of study.
Population: History of chemotherapy for metastatic or recurrent breast cancer (yes/no), History of treatment using a taxane anticancer drug (yes/no), ER status \[ER (+) or ER (-)\], and Disease free interval (\<12 months or ≥12 months) were covariates for adjustment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NK105 | Overall Survival | 31.2 months |
| Paclitaxel | Overall Survival | 36.2 months |
95% CI: [0.885, 1.62]