Doxil & Carboplatin Plus HER2+ in Metastatic Breast Cancer

Study Overview
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Brief Summary
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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).

Official Title
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Phase II Study of Doxil and Carboplatin, Plus Herceptin in HER2+ Patients, in Metastatic Breast Cancer

Conditions
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Metastatic Breast Cancer

Intervention / Treatment
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* Drug: Pegylated liposomal doxorubicin
* Drug: Carboplatin
* Drug: trastuzumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>Patients will receive IV Doxil 30 mg/m2 and carboplatin AUC=5 on Day 1 of each cycle. A cycle consists of 28 days. In addition, HER2+ (IHC3+ and FISH+) patients only will receive a one-time loading dose of Herceptin 8 mg/kg IV on Day 1 of Cycle 1 and 4 mg/kg on Day 1 and Day 15 of every cycle thereafter. | Drug: Pegylated liposomal doxorubicin<br>* 30 mg/m2 IV on Day 1 of each 28 day cycle<br>* Other names: Doxil;Drug: Carboplatin<br>* AUC=5 on Day 1 of each 28 day cycle<br>Drug: trastuzumab<br>* 4 mg/kg on Days 1 and 15 of each cycle(loading dose of 8 mg/kg on Day 1 of Cycle 1 only)<br>* Other names: Herceptin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | From date of randomization until the date of first documented progression or date of intolerable toxicity, whichever came first, assessed up to 54 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response | Duration from date of stating treatment to the date of first CR or PR. | From date of randomization until the date of first documented progression or date of intolerable toxicity, whichever came first, assessed up to 54 months. | 
| 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. | 30 months | 
| 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. | 1 year |