Metastatic Breast Cancer
Conditions
Keywords
Herceptin, Her 2-positive, metastatic breast cancer, CT-P6
Brief summary
The purpose of the study is to demonstrate equivalent pharmacokinetics (PK)
Detailed description
Patients will receive CT-P6 or Herceptin.
Interventions
DRUGCT-P6
CT-P6: administered every 3 weeks
DRUGHerceptin
Herceptin: administered every 3 weeks
DRUGPaclitaxel
Paclitaxel: administered every 3 weeks
Sponsors
Celltrion
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Are females * Have a Her 2 over-expression * Have Eastern Cooperative Oncology Group (ECOG) 0 or 1
Exclusion criteria
* Current clinical or radiographic evidence central nervous system (CNS) metastases * Current Known infection * Pregnant or nursing mother
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration Time Curve at Steady State (AUCss) | 3, 6, 12, 24, 72, 168, 336, 504 hours predose | Area under the concentration time curve at steady state (AUCss), defined as area under the concentration-time curve between Cycle 8 to Cycle 9. The primary endpoint was reached at 6 months (8 treatment cycle; Main Study Treatment Period). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Trough Concentration at Steady State (CtroughSS) | 3, 6, 12, 24, 72, 168, 336, 504 hours predose | Trough concentration at steady state (CtroughSS), defined as trough concentration at steady state. The secondary endpoint was reached at 6 months (8 treatment cycle; Main Study Treatment Period). |
| Cardiotoxicity | Up to approximately 1 year | Cardiac Ejection Fraction Assessment, defined as Mean change from baseline to endpoint assessment in left ventricular ejection fraction (LVEF, Unit: %) from the independent tumor review committee (ITRC). |
| Immunogenicity | every 4 cycles (each cycle is 3 weeks), Up to approximately 5.5 years | Immunogenicity, defined as proportion of patients with antibodies to study drug (positive for antidrug antibody \[ADA\] result after the first study infusion). |
| Overall Response Rate (ORR; Complete Response [CR] Plus Partial Response [PR]) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | every 6 weeks (up to cycle 4) or 12 weeks (after cycle 4) (every cycle is 3 weeks), up to 6 months in Main treatment period and up to 1 year | Overall response rate (ORR) based on best overall response (BOR) during the Main Study Treatment Period and up to 1-year treatment from the independent tumor review committee (ITRC) and Investigator. ORR (complete response \[CR\] plus partial response \[PR\]), as assessed by Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 To be assigned a best ORR of PR or CR, changes in tumour assessments must be confirmed no less than 4 weeks after the criteria for response were met. |
| Serum Human Epidermal Growth Factor Receptor-2 (HER-2) Shed Antigen Value | day 1 of each cycle (every cycle is 3 weeks), Up to approximately 5.5 years | Serum Human epidermal growth factor receptor-2 (HER-2) shed antigen values at baseline (Cycle 1, Day 1) and the last assessments. |
Countries
South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CT-P6 & Paclitaxel CT-P6 was administered at a loading dose of 8 mg/kg body weight by IV infusion over 90 minutes on Day 1, Cycle 1, then at 6 mg/kg repeated at 3-weekly intervals until disease progression, death, or discontinuation.
Paclitaxel was administered at a dose of 175 mg/m2 BSA as a continuous 3-hour IV infusion on the day following the first dose of study drug (CT-P6). If the first dose of study drug was well tolerated, subsequent doses of paclitaxel were given immediately after the next dose of study drug. Paclitaxel cycles were repeated every 3 weeks until disease progression, death, intolerable toxicity, or discontinuation. | 76 |
| Herceptin & Paclitaxel Herceptin was administered at a loading dose of 8 mg/kg body weight by IV infusion over 90 minutes on Day 1, Cycle 1, then at 6 mg/kg repeated at 3-weekly intervals until disease progression, death, or discontinuation.
Paclitaxel was administered at a dose of 175 mg/m2 BSA as a continuous 3-hour IV infusion on the day following the first dose of study drug (Herceptin). If the first dose of study drug was well tolerated, subsequent doses of paclitaxel were given immediately after the next dose of study drug. Paclitaxel cycles were repeated every 3 weeks until disease progression, death, intolerable toxicity, or discontinuation. | 67 |
| Total | 143 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Main Study Treatment Period | Adverse Event | 5 | 3 |
| Main Study Treatment Period | Disease progression | 11 | 7 |
| Main Study Treatment Period | Other Reason | 0 | 1 |
| Treatment Period Beyond Cycle 8 | Adverse Event | 1 | 0 |
| Treatment Period Beyond Cycle 8 | Disease progression | 51 | 45 |
| Treatment Period Beyond Cycle 8 | Other | 0 | 1 |
| Treatment Period Beyond Cycle 8 | Other reason | 2 | 2 |
| Treatment Period Beyond Cycle 8 | Physician Decision | 2 | 4 |
| Treatment Period Beyond Cycle 8 | Withdrawal by Subject | 4 | 4 |
Baseline characteristics
| Characteristic | Total | Herceptin & Paclitaxel | CT-P6 & Paclitaxel |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 21 Participants | 8 Participants | 13 Participants |
| Age, Categorical Between 18 and 65 years | 122 Participants | 59 Participants | 63 Participants |
| Age, Continuous | 54.4 years STANDARD_DEVIATION 10.35 | 53.6 years STANDARD_DEVIATION 10.47 | 55.1 years STANDARD_DEVIATION 10.26 |
| BSA at Screening | 1.71 m2 STANDARD_DEVIATION 0.22 | 1.73 m2 STANDARD_DEVIATION 0.22 | 1.70 m2 STANDARD_DEVIATION 0.22 |
| Childbearing potential No | 101 Participants | 43 Participants | 58 Participants |
| Childbearing potential Yes | 42 Participants | 24 Participants | 18 Participants |
| Eastern Cooperative Oncology Group (ECOG) performance status 0 | 60 Participants | 25 Participants | 35 Participants |
| Eastern Cooperative Oncology Group (ECOG) performance status 1 | 83 Participants | 42 Participants | 41 Participants |
| Height at Screening | 159.6 cm STANDARD_DEVIATION 6.95 | 160.3 cm STANDARD_DEVIATION 7.2 | 158.9 cm STANDARD_DEVIATION 6.7 |
| Karnofsky performance status Category 1 | 134 Participants | 62 Participants | 72 Participants |
| Karnofsky performance status Category 2 | 4 Participants | 3 Participants | 1 Participants |
| Karnofsky performance status Category 3 | 0 Participants | 0 Participants | 0 Participants |
| Karnofsky performance status Not reported | 5 Participants | 2 Participants | 3 Participants |
| Prior chemotherapy No | 88 Participants | 41 Participants | 47 Participants |
| Prior chemotherapy Yes | 55 Participants | 26 Participants | 29 Participants |
| Race/Ethnicity, Customized Asian | 63 Participants | 32 Participants | 31 Participants |
| Race/Ethnicity, Customized White | 80 Participants | 35 Participants | 45 Participants |
| Region of Enrollment Bulgaria | 8 Participants | 2 Participants | 6 Participants |
| Region of Enrollment Latvia | 13 Participants | 6 Participants | 7 Participants |
| Region of Enrollment Russia | 35 Participants | 16 Participants | 19 Participants |
| Region of Enrollment Serbia | 9 Participants | 5 Participants | 4 Participants |
| Region of Enrollment South Korea | 63 Participants | 32 Participants | 31 Participants |
| Region of Enrollment Ukraine | 15 Participants | 6 Participants | 9 Participants |
| Sex: Female, Male Female | 143 Participants | 67 Participants | 76 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Weight at Screening | 66.7 kg STANDARD_DEVIATION 16.17 | 67.6 kg STANDARD_DEVIATION 15.71 | 66.0 kg STANDARD_DEVIATION 16.64 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 76 | 3 / 67 |
| other Total, other adverse events | 74 / 76 | 64 / 67 |
| serious Total, serious adverse events | 12 / 76 | 19 / 67 |
Outcome results
Primary
Area Under the Concentration Time Curve at Steady State (AUCss)
Area under the concentration time curve at steady state (AUCss), defined as area under the concentration-time curve between Cycle 8 to Cycle 9. The primary endpoint was reached at 6 months (8 treatment cycle; Main Study Treatment Period).
Time frame: 3, 6, 12, 24, 72, 168, 336, 504 hours predose
Population: PK Analysis Set - Global (PKASg) was defined as all FAS patients who had achieved steady state by the 8th cycle, which required three consecutive similar trough concentrations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CT-P6 & Paclitaxel | Area Under the Concentration Time Curve at Steady State (AUCss) | 34400 ug*h/mL | Standard Deviation 15000 |
| Herceptin & Paclitaxel | Area Under the Concentration Time Curve at Steady State (AUCss) | 31800 ug*h/mL | Standard Deviation 9820 |
90% CI: [93.64, 116.78]
Secondary
Cardiotoxicity
Cardiac Ejection Fraction Assessment, defined as Mean change from baseline to endpoint assessment in left ventricular ejection fraction (LVEF, Unit: %) from the independent tumor review committee (ITRC).
Time frame: Up to approximately 1 year
Population: Safety Analysis Set (SAF) was defined as all patients in the FAS. All patients receiving at least one dose of CT-P6 were analyzed under the CT-P6 treatment group. All other patients were analyzed under the Herceptin treatment group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CT-P6 & Paclitaxel | Cardiotoxicity | -5.49 %; percentage of LVEF | Standard Deviation 6.543 |
| Herceptin & Paclitaxel | Cardiotoxicity | -6.43 %; percentage of LVEF | Standard Deviation 5.622 |
Secondary
Immunogenicity
Immunogenicity, defined as proportion of patients with antibodies to study drug (positive for antidrug antibody \[ADA\] result after the first study infusion).
Time frame: every 4 cycles (each cycle is 3 weeks), Up to approximately 5.5 years
Population: Safety Analysis Set (SAF) was defined as all patients in the FAS. All patients receiving at least one dose of CT-P6 were analyzed under the CT-P6 treatment group. All other patients were analyzed under the Herceptin treatment group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CT-P6 & Paclitaxel | Immunogenicity | 2 Participants |
| Herceptin & Paclitaxel | Immunogenicity | 0 Participants |
Secondary
Overall Response Rate (ORR; Complete Response [CR] Plus Partial Response [PR]) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Overall response rate (ORR) based on best overall response (BOR) during the Main Study Treatment Period and up to 1-year treatment from the independent tumor review committee (ITRC) and Investigator. ORR (complete response \[CR\] plus partial response \[PR\]), as assessed by Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 To be assigned a best ORR of PR or CR, changes in tumour assessments must be confirmed no less than 4 weeks after the criteria for response were met.
Time frame: every 6 weeks (up to cycle 4) or 12 weeks (after cycle 4) (every cycle is 3 weeks), up to 6 months in Main treatment period and up to 1 year
Population: Full Analysis Set (FAS) was defined as all randomized patients who received any study drug (CT-P6 or Herceptin) and had at least one post-baseline assessment, with the exception of the patients who violated against Herceptin indication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CT-P6 & Paclitaxel | Overall Response Rate (ORR; Complete Response [CR] Plus Partial Response [PR]) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Main Study Treatment Period | 61.8 percentage of responder |
| CT-P6 & Paclitaxel | Overall Response Rate (ORR; Complete Response [CR] Plus Partial Response [PR]) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 1 Year | 65.8 percentage of responder |
| Herceptin & Paclitaxel | Overall Response Rate (ORR; Complete Response [CR] Plus Partial Response [PR]) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Main Study Treatment Period | 76.1 percentage of responder |
| Herceptin & Paclitaxel | Overall Response Rate (ORR; Complete Response [CR] Plus Partial Response [PR]) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 1 Year | 77.6 percentage of responder |
| CT-P6 & Paclitaxel Investigator | Overall Response Rate (ORR; Complete Response [CR] Plus Partial Response [PR]) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 1 Year | 72.4 percentage of responder |
| CT-P6 & Paclitaxel Investigator | Overall Response Rate (ORR; Complete Response [CR] Plus Partial Response [PR]) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Main Study Treatment Period | 68.4 percentage of responder |
| Herceptin & Paclitaxel Investigator | Overall Response Rate (ORR; Complete Response [CR] Plus Partial Response [PR]) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 1 Year | 80.6 percentage of responder |
| Herceptin & Paclitaxel Investigator | Overall Response Rate (ORR; Complete Response [CR] Plus Partial Response [PR]) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Main Study Treatment Period | 80.6 percentage of responder |
Secondary
Serum Human Epidermal Growth Factor Receptor-2 (HER-2) Shed Antigen Value
Serum Human epidermal growth factor receptor-2 (HER-2) shed antigen values at baseline (Cycle 1, Day 1) and the last assessments.
Time frame: day 1 of each cycle (every cycle is 3 weeks), Up to approximately 5.5 years
Population: Safety Analysis Set (SAF) was defined as all patients in the FAS. All patients receiving at least one dose of CT-P6 were analyzed under the CT-P6 treatment group. All other patients were analyzed under the Herceptin treatment group.~One subject in the CT-P6 treatment group did not have baseline HER-2 Shed antigen result.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CT-P6 & Paclitaxel | Serum Human Epidermal Growth Factor Receptor-2 (HER-2) Shed Antigen Value | Baseline (Cycle 1, Day 1) | 85.20 ng/mL | Standard Deviation 195.1 |
| CT-P6 & Paclitaxel | Serum Human Epidermal Growth Factor Receptor-2 (HER-2) Shed Antigen Value | Last assessment | 49.68 ng/mL | Standard Deviation 162.1 |
| Herceptin & Paclitaxel | Serum Human Epidermal Growth Factor Receptor-2 (HER-2) Shed Antigen Value | Baseline (Cycle 1, Day 1) | 77.87 ng/mL | Standard Deviation 169.14 |
| Herceptin & Paclitaxel | Serum Human Epidermal Growth Factor Receptor-2 (HER-2) Shed Antigen Value | Last assessment | 8.82 ng/mL | Standard Deviation 19.97 |
Secondary
Trough Concentration at Steady State (CtroughSS)
Trough concentration at steady state (CtroughSS), defined as trough concentration at steady state. The secondary endpoint was reached at 6 months (8 treatment cycle; Main Study Treatment Period).
Time frame: 3, 6, 12, 24, 72, 168, 336, 504 hours predose
Population: PK Analysis Set - Global (PKASg) was defined as all FAS patients who had achieved steady state by the 8th cycle, which required three consecutive similar trough concentrations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CT-P6 & Paclitaxel | Trough Concentration at Steady State (CtroughSS) | 21.1 ug/mL | Standard Deviation 7.83 |
| Herceptin & Paclitaxel | Trough Concentration at Steady State (CtroughSS) | 20.8 ug/mL | Standard Deviation 8.26 |