Breast Cancer
Conditions
Keywords
Breast Cancer, Advanced breast cancer, Breast Tumors, Cancer of Breast, Human Mammary Carcinoma, Mammary Neoplasms, Human, DOXIL, Docetaxel
Brief summary
The purpose of the study is to evaluate whether the time to progression for the DOXIL and docetaxel combination therapy group was superior to that of the group treated with docetaxel monotherapy in participants with advanced breast cancer.
Detailed description
This is a randomized (the study medication is assigned by a random order), active control (study medication will be compared with available standard care of treatment), parallel-group (each treatment group will be treated simultaneously at the same time and each participant only receives one treatment regimen as assigned), open-label (both the investigator and the participant know the intervention received by the participant), multicenter study designed to determine if women with locally advanced or metastatic breast cancer, who were previously treated with prior anthracycline therapy in the neoadjuvant (administration of treatment before surgery) or adjuvant setting (administration of treatment after surgery), and who also had a disease-free interval of at least 12 months since the end of their last cytotoxic therapy, would benefit from the addition of DOXIL to docetaxel therapy. Approximately 751 participants will be randomly assigned to either receive docetaxel monotherapy or DOXIL in combination with docetaxel therapy. Treatment is to continue until disease progression or the occurrence of unacceptable treatment related toxicity. Safety evaluations will include assessments of adverse events which will be recorded from the first study related procedure until 30 days after the last dose of medication; clinical laboratory tests and tests for cardiac function (multiple gated acquisition scan/echocardiogram and electrocardiogram) which will be monitored throughout the study.
Interventions
DRUGDocetaxel
Docetaxel monotherapy: docetaxel 75 mg/m2 solution administered by intravenous infusion over 1 hour on Day 1 of every 21-day cycle. DOXIL in combination with docetaxel: docetaxel 60 mg/m2 solution administered by intravenous infusion over 1 hour on Day 1 of every 21-day cycle
DRUGDOXIL
DOXIL 30 mg/m2 solution administered by intravenous infusion over 1 hour on Day 1 of every 21-day cycle.
Sponsors
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
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
* Females with locally advanced or metastatic breast cancer who received prior anthracycline therapy in the neoadjuvant or adjuvant setting, and had at least a 12-month disease-free interval since the end of their last cytotoxic therapy, were eligible for the study * Participants who received prior hormonal therapy, or no more than 1 cytotoxic chemotherapy regimen (anthracyclines, taxanes, or antitubulin agents were not permitted), or both for advanced disease * Participants with normal cardiac function, as evidenced by a normal left ventricular ejection fraction
Exclusion criteria
* More than 1 prior cytotoxic chemotherapy regimen for advanced breast cancer * Treatment of advanced breast cancer with an anthracycline, paclitaxel, docetaxel, vinorelbine, or vinblastine (prior treatment of advanced breast cancer with 1 regimen that included alkylating agents or antimetabolite agents was acceptable) * Less than 2 months since the last dose of trastuzumab * Less than 3 weeks since last dose of tamoxifen or fulvestrant, or less than 1 week since the last dose of other hormonal therapy * Radiation to areas of disease within 30 days before study enrollment * History of New York Heart Association Class II or greater cardiac disease or other clinical evidence of congestive heart failure
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression | From date of randomization until date of disease progression or death, whichever occurred first, until approximately 485 events of disease progression or death were observed, as assessed approximately 15 months after the last patient was enrolled | Time interval in months between the date of randomization and the date of disease progression or death due to progression, whichever occurred first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | From the date of randomization until the participant's death from any cause, as assessed until approximately 485 death events were observed which is assessed approximately 25 months after the last patient was enrolled | Time interval in months between the date of randomization and the participant's death from any cause. |
| Response Rate: Number of Participants in the Evaluable Population Who Achieved a Complete Response (CR) or Partial Response (PR) | Up to 30 to 42 days after last dose of study medication | Number of participants in the evaluable population who achieved a CR or PR as per Response Evaluation Criteria In Solid Tumors (RECIST) criteria. CR: Disappearance of all target lesions and PR: at least a 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the baseline sum LD. Response was assessed by Computed Tomography (CT)/Magnetic Resonance Imaging (MRI). |
Countries
Bulgaria, Estonia, France, Hungary, Israel, Latvia, Lithuania, Netherlands, Poland, Portugal, Romania, Russia, Serbia, South Africa, Spain, Ukraine, United Kingdom, United States
Participant flow
Recruitment details
A total of 751 participants were enrolled and randomized at 143 sites in 19 countries.
Pre-assignment details
751 participants were randomly assigned to 2 treatment groups (Docetaxel: 373 ; DOXIL+docetaxel: 378). 750 participants received treatment (Docetaxel: 373; DOXIL+docetaxel: 377). 1 participant in DOXIL+docetaxel treatment group did not receive treatment.
Participants by arm
| Arm | Count |
|---|---|
| Docetaxel Docetaxel monotherapy: Docetaxel 75 mg/m2 solution administered by intravenous infusion over 1 hour on Day 1 of every 21-day cycle. | 373 |
| DOXIL+Docetaxel DOXIL and docetaxel combination: DOXIL 30 mg/m2 solution administered by intravenous infusion, followed by docetaxel 60 mg/m2 administration by intravenous infusion over 1 hour on Day 1 of every 21-day cycle. | 378 |
| Total | 751 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | 2cycles therapy beyond Complete response | 9 | 16 |
| Overall Study | Adverse Event | 29 | 48 |
| Overall Study | Death | 9 | 7 |
| Overall Study | Lost to Follow-up | 1 | 3 |
| Overall Study | Other | 2 | 6 |
| Overall Study | Physician Decision | 61 | 58 |
| Overall Study | Progressive Disease | 220 | 189 |
| Overall Study | Withdrawal by Subject | 38 | 46 |
Baseline characteristics
| Characteristic | Docetaxel | DOXIL+Docetaxel | Total |
|---|---|---|---|
| Age, Continuous | 52.0 years STANDARD_DEVIATION 9.23 | 52.8 years STANDARD_DEVIATION 9.17 | 52.4 years STANDARD_DEVIATION 9.2 |
| Sex: Female, Male Female | 373 Participants | 378 Participants | 751 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 | 340 / 373 | 359 / 377 |
| serious Total, serious adverse events | 59 / 373 | 69 / 377 |
Outcome results
Primary
Time to Progression
Time interval in months between the date of randomization and the date of disease progression or death due to progression, whichever occurred first.
Time frame: From date of randomization until date of disease progression or death, whichever occurred first, until approximately 485 events of disease progression or death were observed, as assessed approximately 15 months after the last patient was enrolled
Population: Intent to Treat: For patients who were progression free at the time of data cutoff, data were censored for time to progression at the time of their last tumor assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Docetaxel | Time to Progression | 7.0 Months |
| DOXIL+Docetaxel | Time to Progression | 9.8 Months |
Comparison: Null hypothersis - no difference in Time to Progression (TTP) between the two treatment groups.~Designed to detect an improvement in median TTP from 6 months to 7.8 months with 80% power, assuming exponential survival distribution.p-value: <0.000195% CI: [0.55, 0.77]Log Rank
Secondary
Overall Survival
Time interval in months between the date of randomization and the participant's death from any cause.
Time frame: From the date of randomization until the participant's death from any cause, as assessed until approximately 485 death events were observed which is assessed approximately 25 months after the last patient was enrolled
Population: Intent to Treat: If the date of death was unknown, the data were censored at the date that the participant was last known to have been alive.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Docetaxel | Overall Survival | 20.7 Months |
| DOXIL+Docetaxel | Overall Survival | 20.4 Months |
Comparison: Null Hypothesis: Designed to detect an improvement in median survival from 15 months to 19.5 months with 80% power.p-value: 0.598895% CI: [0.86, 1.3]Log Rank
Secondary
Response Rate: Number of Participants in the Evaluable Population Who Achieved a Complete Response (CR) or Partial Response (PR)
Number of participants in the evaluable population who achieved a CR or PR as per Response Evaluation Criteria In Solid Tumors (RECIST) criteria. CR: Disappearance of all target lesions and PR: at least a 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the baseline sum LD. Response was assessed by Computed Tomography (CT)/Magnetic Resonance Imaging (MRI).
Time frame: Up to 30 to 42 days after last dose of study medication
Population: Evaluable population: Included all randomized participants who received at least 1 dose of study medication (DOXIL or docetaxel), and who had at least 1 postbaseline tumor assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Docetaxel | Response Rate: Number of Participants in the Evaluable Population Who Achieved a Complete Response (CR) or Partial Response (PR) | 95 Participants |
| DOXIL+Docetaxel | Response Rate: Number of Participants in the Evaluable Population Who Achieved a Complete Response (CR) or Partial Response (PR) | 129 Participants |
Comparison: Null hypothesis - no difference in response rate between the two treatment groups.p-value: 0.0085Cochran-Mantel-Haenszel