Metastatic Breast Cancer
Conditions
Brief summary
The purpose of this study is to determine the ORR associated with Doxil in combination with carboplatin in HER2- (negative) MBC (and with Herceptin in HER2+ MBC).
Interventions
DRUGPegylated liposomal doxorubicin
30 mg/m2 IV on Day 1 of each 28 day cycle
DRUGCarboplatin
AUC=5 on Day 1 of each 28 day cycle
DRUGtrastuzumab
4 mg/kg on Days 1 and 15 of each cycle(loading dose of 8 mg/kg on Day 1 of Cycle 1 only)
Sponsors
Ortho Biotech, Inc.
Tibotec Pharmaceutical Limited
US Oncology Research
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has metastatic breast cancer with documented HER2- or HER2+ (IHC3+ or FISH+) disease * Has measurable MBC, with at least 1 measurable lesion per RECIST criteria (see Section 10). Irradiated lesions cannot be used to assess response but can be used to assess progression. * Has had no prior treatment with Doxil or carboplatin; may have had adjuvant Herceptin if treatment was completed more than 1 year prior to study * Has had no adjuvant chemotherapy within 1 year prior to study, but may have received prior anthracyclines as adjuvant chemotherapy * For taxane-pretreated patients (adjuvant or metastatic), has had no more than 1 prior chemotherapy regimen for MBC * For taxane-naïve patients, has had no prior chemotherapy for MBC * Has had cumulative doses of \< 300 mg/m2 prior doxorubicin or \< 450 mg/m2 prior epirubicin * Has normal cardiac function as evidenced by a LVEF within institutional normal limits by multiple gated acquisition (MUGA) scan. An echocardiogram (ECHO) may be used if MUGA is not available, but the same test must be used throughout the study to evaluate LVEF. * Has an ECOG Performance Status (PS) 0-2 (see Appendix I) * Is a male or female greater than or equal to 18 years of age * Laboratory Values - Please refer to protocol section 4.2 for specific laboratory values. * Has a negative serum pregnancy test within 7 days prior to registration (woman of childbearing potential \[WOCBP; not surgically sterilized and between menarche and 1 year postmenopause\]) * If fertile, patient (male or female) has agreed to use an acceptable method of birth control (eg, abstinence, intrauterine device, oral contraceptives, barrier device with spermicide or surgical sterilization) to avoid pregnancy for the duration of the study and for a period of 3 months thereafter. * Has signed a Patient Informed Consent Form * Has signed a Patient Authorization Form (HIPAA Form) * Has a life expectancy of \> 3 months
Exclusion criteria
* Has had a myocardial infarction (MI) within 6 months of trial enrollment, or has New York Heart Association (NYHA; see Appendix IV) Class II or greater heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, clinically significant pericardial disease, or electrocardiographic evidence of acute ischemic or active conduction system abnormalities * Has a history of hypersensitivity reactions attributed to a conventional formulation of doxorubicin HCL or the components of Doxil * Has evaluable only disease; eg, bone only, pleural, peritoneal only disease * Is receiving concurrent immunotherapy, hormonal therapy, or radiation therapy. Patients receiving immunosuppressant therapy for autoimmune disease may enroll on the trial after a drug washout period of 2 weeks. * Is receiving concurrent investigational therapy or has received such therapy within 30 days * Has evidence of brain metastases requiring steroids and/or radiation or any documented leptomeningeal disease * Has a serious uncontrolled intercurrent medical or psychiatric illness, including serious infection or history of uncontrolled seizures, CNS disorders deemed by the Treating Physician to be clinically significant, precluding informed consent * Has a history of other malignancy within the last 5 years (except cured basal cell carcinoma of skin and carcinoma in situ of uterine cervix), which could affect the diagnosis or assessment of any of the study drugs * Is a pregnant or lactating woman * Is unable to comply with requirements of study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | From date of randomization until the date of first documented progression or date of intolerable toxicity, whichever came first, assessed up to 54 months. | 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; Objective response (OR) = CR + PR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response | From date of randomization until the date of first documented progression or date of intolerable toxicity, whichever came first, assessed up to 54 months. | Duration from date of stating treatment to the date of first CR or PR. |
| Progression-free Survival (PFS) | 30 months | PFS is measured from the date of randomization to the date of first documented disease progression or date of death, whichever comes first. If a patient neither progresses nor dies, this patient will be censored at last contact date. Progression is defined as appearance of one or more new lesions. Unequivocal progression of existing non-target lesions. Although a clear progression of non-target lesions only is exceptional, in such circumstances, the opinion of the Treating Physician should prevail, and the progression status should be confirmed at a later time by the review panel. |
| 1-year Overall Survival | 1 year | OS is measured from the date of randomization to the date of death for a dead patient. If a patient is still alive or is lost to follow up, the patient will be censored at the last contact date. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| D+C and Taxane Naive Doxil, Carboplatin and Taxane naive | 43 |
| D+C and Taxane Pretreated Doxil, Carboplatin and Taxane pretreated | 46 |
| D+C+H Doxil, Carboplatin, and Herceptin | 47 |
| Total | 136 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 5 | 6 | 7 |
| Overall Study | Failed Entry | 1 | 0 | 1 |
| Overall Study | ineligible | 2 | 1 | 0 |
| Overall Study | Patient Request | 4 | 2 | 8 |
Baseline characteristics
| Characteristic | D+C and Taxane Naive | D+C and Taxane Pretreated | D+C+H | Total |
|---|---|---|---|---|
| Age, Continuous | 61.0 years | 51.7 years | 54.1 years | 56.4 years |
| Race/Ethnicity, Customized Black | 10 participants | 8 participants | 7 participants | 25 participants |
| Race/Ethnicity, Customized Caucasian | 30 participants | 34 participants | 37 participants | 101 participants |
| Race/Ethnicity, Customized Hawaiian | 0 participants | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Hispanic | 3 participants | 4 participants | 2 participants | 9 participants |
| Region of Enrollment United States | 43 participants | 46 participants | 47 participants | 136 participants |
| Sex: Female, Male Female | 42 Participants | 46 Participants | 47 Participants | 135 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 80 / 83 | 44 / 46 |
| serious Total, serious adverse events | 8 / 83 | 3 / 46 |
Outcome results
Primary
Objective Response Rate (ORR)
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; Objective response (OR) = CR + PR.
Time frame: From date of randomization until the date of first documented progression or date of intolerable toxicity, whichever came first, assessed up to 54 months.
Population: Evaluable population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| D+C and Taxane Naive | Objective Response Rate (ORR) | 30.8 percentage of participants |
| D+C and Taxane Pretreated | Objective Response Rate (ORR) | 31.0 percentage of participants |
| D+C+H | Objective Response Rate (ORR) | 55.6 percentage of participants |
Secondary
1-year Overall Survival
OS is measured from the date of randomization to the date of death for a dead patient. If a patient is still alive or is lost to follow up, the patient will be censored at the last contact date.
Time frame: 1 year
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| D+C and Taxane Naive | 1-year Overall Survival | 0.83 probability of overall survival |
| D+C and Taxane Pretreated | 1-year Overall Survival | 0.56 probability of overall survival |
| D+C+H | 1-year Overall Survival | 0.90 probability of overall survival |
Secondary
Duration of Response
Duration from date of stating treatment to the date of first CR or PR.
Time frame: From date of randomization until the date of first documented progression or date of intolerable toxicity, whichever came first, assessed up to 54 months.
Population: Patients who achieved CR or PR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| D+C and Taxane Naive | Duration of Response | 11.1 months |
| D+C and Taxane Pretreated | Duration of Response | 7.0 months |
| D+C+H | Duration of Response | 11.8 months |
Secondary
Progression-free Survival (PFS)
PFS is measured from the date of randomization to the date of first documented disease progression or date of death, whichever comes first. If a patient neither progresses nor dies, this patient will be censored at last contact date. Progression is defined as appearance of one or more new lesions. Unequivocal progression of existing non-target lesions. Although a clear progression of non-target lesions only is exceptional, in such circumstances, the opinion of the Treating Physician should prevail, and the progression status should be confirmed at a later time by the review panel.
Time frame: 30 months
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| D+C and Taxane Naive | Progression-free Survival (PFS) | 8.1 months |
| D+C and Taxane Pretreated | Progression-free Survival (PFS) | 5.4 months |
| D+C+H | Progression-free Survival (PFS) | 10.1 months |