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Doxil & Carboplatin Plus HER2+ in Metastatic Breast Cancer

Phase 2
Completed
Conditions
Metastatic Breast Cancer
Interventions
Registration Number
NCT00303108
Lead Sponsor
US Oncology Research
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).

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
136
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Arm 1Pegylated liposomal doxorubicinPatients 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.
Arm 1trastuzumabPatients 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.
Arm 1CarboplatinPatients 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.
Primary Outcome Measures
NameTimeMethod
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 Outcome Measures
NameTimeMethod
Duration of ResponseFrom 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 Survival1 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.

Trial Locations

Locations (53)

Missouri Cancer Associates

🇺🇸

Columbia, Missouri, United States

Texas Cancer Center

🇺🇸

Arlington, Texas, United States

Hematology Oncology Associates of IL

🇺🇸

Chicago, Illinois, United States

Central Indiana Cancer Centers

🇺🇸

Indianapolis, Indiana, United States

Comprehensive Cancer Centers of Nevada

🇺🇸

Las Vegas, Nevada, United States

Texas Oncology, PA

🇺🇸

Houston, Texas, United States

Minnesota Oncology Hematology, PA

🇺🇸

Minneapolis, Minnesota, United States

Hematology Oncology Associates

🇺🇸

Phoenix, Arizona, United States

New Mexico Cancer Care Associates

🇺🇸

Santa Fe, New Mexico, United States

Northern AZ Hematology & Oncology Associates-Sedona

🇺🇸

Sedona, Arizona, United States

Florida Cancer Institute

🇺🇸

New Port Richey, Florida, United States

Ocala Oncology Center

🇺🇸

Ocala, Florida, United States

Cancer Care & Hematology Specialists of Chicagoland, PC

🇺🇸

Niles, Illinois, United States

Kansas City Cancer Centers-Southwest

🇺🇸

Overland Park, Kansas, United States

Maryland Oncology Hematology, PA

🇺🇸

Columbia, Maryland, United States

Flavio Kruter, MD, PA

🇺🇸

Westminster, Maryland, United States

New York Oncology Hematology, PC

🇺🇸

Albany, New York, United States

Texas Oncology, P.A.-Amarillo

🇺🇸

Amarillo, Texas, United States

Texas Cancer Center - Abilene (South)

🇺🇸

Abilene, Texas, United States

Raleigh Hematology Oncology Associates

🇺🇸

Cary, North Carolina, United States

Ruth Oratz MD

🇺🇸

New York, New York, United States

Greater Dayton Cancer Center

🇺🇸

Kettering, Ohio, United States

Texas Oncology, PA-Bedford

🇺🇸

Bedford, Texas, United States

Texas Cancer Center at Medical City

🇺🇸

Dallas, Texas, United States

Mamie McFaddin Ward Cancer Center

🇺🇸

Beaumont, Texas, United States

Texas Cancer Center-Denton

🇺🇸

Denton, Texas, United States

The TexasCancer Center

🇺🇸

Dallas, Texas, United States

El Paso Cancer Treatment Ctr

🇺🇸

El Paso, Texas, United States

Lake Vista Cancer Center

🇺🇸

Lewisville, Texas, United States

South Texas Cancer Center-McAllen

🇺🇸

McAllen, Texas, United States

Longview Cancer Center

🇺🇸

Longview, Texas, United States

Texas Cancer Center of Mesquite

🇺🇸

Mesquite, Texas, United States

Paris Regional Cancer Center

🇺🇸

Paris, Texas, United States

Alison Cancer Center

🇺🇸

Midland, Texas, United States

West Texas Cancer Center

🇺🇸

Odessa, Texas, United States

HOAST-Medical Dr.

🇺🇸

San Antonio, Texas, United States

Texas Cancer Center-Sherman

🇺🇸

Sherman, Texas, United States

Tyler Cancer Center

🇺🇸

Tyler, Texas, United States

Texas Oncology Cancer Center-Sugar Land

🇺🇸

Sugar Land, Texas, United States

Texas Oncology Cancer Care and Research Center-Waco

🇺🇸

Waco, Texas, United States

Texas Oncology, P.A.

🇺🇸

Webster, Texas, United States

Virginia Oncology Associates

🇺🇸

Norfolk, Virginia, United States

Fairfax Northern VA Hem-Onc PC

🇺🇸

Fairfax, Virginia, United States

Onc and Hem Associates of SW VA, Inc

🇺🇸

Salem, Virginia, United States

Puget Sound Cancer Center-Edmonds

🇺🇸

Edmonds, Washington, United States

Puget Sound Cancer Center-Seattle

🇺🇸

Seattle, Washington, United States

Northwest Cancer Specialists-Vancouver

🇺🇸

Vancouver, Washington, United States

Cancer Care Northwest-North

🇺🇸

Spokane, Washington, United States

Yakima Valley Mem Hosp/North Star Lodge

🇺🇸

Yakima, Washington, United States

Medical Oncology Associates

🇺🇸

Kingston, Pennsylvania, United States

Willamette Vallejy Cancer Center

🇺🇸

Eugene, Oregon, United States

Birmingham Hematology and Oncology

🇺🇸

Birmingham, Alabama, United States

Rocky Mountain Cancer Center-Rose

🇺🇸

Denver, Colorado, United States

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