Trial of Amrubicin as Treatment for Patients With HER2-Negative Metastatic Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01033032
Recruitment Status : Completed
First Posted : December 16, 2009
Results First Posted : January 6, 2015
Last Update Posted : January 6, 2015
Celgene Corporation
Information provided by (Responsible Party):
SCRI Development Innovations, LLC

Brief Summary:
Doxorubicin has been an integral part of the treatment of women with breast cancer for many years. Since amrubicin may have more activity than doxorubicin, as well as less cardiotoxicity, evaluation of amrubicin in the treatment of advanced breast cancer should be a priority. In this Phase II study, the investigators propose an evaluation of single-agent amrubicin as second- or third-line treatment for women with metastatic breast cancer.

Condition or disease Intervention/treatment Phase
Metastatic Breast Cancer Drug: Amrubicin Phase 1 Phase 2

Detailed Description:
This will be a phase I/II study where phase I will evaluate the maximum tolerated dose of amrubicin, and phase II will assess the progression free survival of patients with HER2-negative metastatic breast cancer using the dose established in the phase I portion.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 78 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Trial of Amrubicin as Second- or Third-Line Treatment for Patients With HER2-Negative Metastatic Breast Cancer
Study Start Date : December 2009
Actual Primary Completion Date : July 2013
Actual Study Completion Date : October 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Amrubicin Phase I/II
Systemic therapy with amrubicin
Drug: Amrubicin

Phase I: dose escalating portion with the starting dose of amrubicin at 90mg/m2 IV q21 days. Dose escalations are as follows:

DL2 - 100mg/m2; DL3 - 110mg/m2; and DL4 - 120mg/m2. All cycles are q21 days

Phase II: Amrubicin will be administered at the maximum tolerated dose established in Phase I by IV every 21 days

Other Name: Systemic therapy

Primary Outcome Measures :
  1. Progression-free Survival (PFS) [ Time Frame: every 6 weeks until progressive disease ]
    Progression-free survival is measured from Day 1 of study drug administration to disease progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death on study. Progression is defined in RECIST v1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Secondary Outcome Measures :
  1. Number of Patients With Adverse Events as a Measure of Safety and Tolerability [ Time Frame: every 6 weeks until treatment discontinuation, expected average 18 months ]
    Assessments will be made through analysis of the reported incidence of treatment-emergent Serious Adverse Events (SAEs) and non-serious adverse events (AEs)

  2. Overall Survival (OS) [ Time Frame: every 6 weeks until treatment discontinuation, expected average of 18 months ]
    Measured from Day 1 of study drug administration to date of death due to any cause.

  3. Overall Response Rate (ORR) [ Time Frame: every 6 weeks until treatment discontinuation, expected average 18 months ]
    The number of patients with observed complete response [CR] or partial response [PR]. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) 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; Overall Response (OR) = CR + PR

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Females >=18 years of age.
  2. Histologic diagnosis of HER2-negative breast cancer. HER-2 negativity must be confirmed by one of the following:

    • FISH-negative (FISH ratio <2.2), or
    • IHC 0-1+, or
    • IHC 2-3+ AND FISH-negative (FISH ratio <2.2)
  3. Evidence of metastatic or locally advanced, inoperable breast cancer.
  4. Minimum of 1 and maximum of 2 prior metastatic breast cancer chemotherapy regimens.
  5. Patients with prior anthracycline therapy are eligible, provided their previous anthracycline was ≥6 months prior to study entry.
  6. Measurable disease per RECIST criteria version 1.1
  7. Left ventricular ejection fraction (LVEF) ³50% by echocardiogram (ECHO) or multiple gated acquisition scan (MUGA).
  8. Patients must have QTc interval of <=450 msec.
  9. No intercurrent significant medical conditions or cardiac illness.
  10. Patients must be >=3 weeks since last chemotherapy, and recovered from all acute toxicities, with the exception of alopecia.
  11. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2.
  12. Adequate organ function including the following:

    • ANC >=1500 cells/mL
    • Platelet count >=100,000 cells/mL
    • Hemoglobin >=9 g/dL
    • Total bilirubin <=1.5 x ULN; AST/ALT <=2.5 x ULN, (except if due to hepatic metastases, then <=5 x ULN)
    • Serum creatinine <1.5 x ULN
  13. Women of childbearing potential must have a negative serum or urine pregnancy test performed <=7 days prior to start of treatment. If a woman becomes pregnant or suspects she is pregnant while participating in this study, she must agree to inform her treating physician immediately.
  14. Patients must be accessible for treatment and follow-up.
  15. Patients must be able to understand the investigational nature of this study and give written informed consent prior to study entry.
  16. Patients who are on anticoagulation are acceptable if the therapeutic anticoagulation is stable. Additionally, the patient's INR must be adequate if the patient is receiving treatment with coumadin.
  17. Prior hormonal therapy for metastatic breast cancer is permitted; however, the therapy must be discontinued prior to the patient's enrollment in this study.

Exclusion Criteria:

  1. Any concurrent therapy with other investigational, chemotherapeutic, or hormonal therapy.
  2. Prior treatment with >=3 regimens of cytotoxic therapy in the advanced disease setting. (Any number of previous hormonal therapies are acceptable, as long as the therapy is discontinued prior to the patient's enrollment into this study).
  3. Major surgery or systemic therapy <=3 weeks of study treatment.
  4. Prior high-dose chemotherapy requiring hematopoietic stem cell support.
  5. Prior radiation therapy to >25% of the bone marrow.
  6. Uncontrolled brain metastases. Patients with treated brain metastases (resection or radiotherapy) are eligible if brain metastases have responded to treatment as documented by CT or MRI scan obtained at >=2 weeks after completion of radiation therapy, neurologic symptoms are absent, and steroids have been discontinued.
  7. Suspected, diffuse idiopathic interstitial lung disease or pulmonary fibrosis.
  8. Diagnosis of second malignancy within the last 3 years (with the exception of carcinoma in situ of the cervix, squamous or basal cell skin cancer, thyroid cancer, ductal carcinoma in situ [DCIS], or lobular carcinoma in situ [LCIS]).
  9. Any of the following <=12 months prior to starting study treatment:

    • myocardial infarction;
    • severe unstable angina;
    • congestive heart failure;
    • ongoing cardiac dysrhythmia.
  10. Family history of idiopathic cardiomyopathy or uncontrolled heart arrhythmia.
  11. Patients with previous allergy or hypersensitivity to anthracyclines.
  12. Patients who have had a ≥10% drop in LVEF on previous anthracycline therapy.
  13. Palliative radiotherapy to areas of metastatic breast cancer must have been completed >7 days prior to the first dose of study treatment. The exception is radiotherapy for brain metastases, which must be completed >=21 days prior to study treatment. (Note: Any measurable lesion that has been previously irradiated will not be considered as a target lesion).
  14. Concurrent severe, intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.
  15. History of seropositive HIV, or patients who are receiving immunosuppressive medications that increase the risk of neutropenic complications.
  16. Mental condition that would prevent patient comprehension of the nature of, and risk associated with, the study.
  17. Use of any non-approved or investigational agent <=30 days of administration of the first dose of study drug. Patients may not receive any other investigational or anti-cancer treatments while participating in this study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01033032

United States, Arkansas
NEA Baptist Clinic
Jonesboro, Arkansas, United States, 72401
United States, Florida
Florida Cancer Specialists
Fort Myers, Florida, United States, 33901
United States, Georgia
Northeast Georgia Medical Center
Gainesville, Georgia, United States, 30501
United States, Kentucky
Baptist Hospital East
Louisville, Kentucky, United States, 40207
Norton Cancer Institute
Louisville, Kentucky, United States, 40207
United States, Louisiana
Hematology Oncology Clinic, LLP
Baton Rouge, Louisiana, United States, 70809
United States, Maryland
Center for Cancer and Blood Disorders
Bethesda, Maryland, United States, 20817
National Capital Clinical Research Consortium
Bethesda, Maryland, United States, 20817
United States, Michigan
Grand Rapids Clinical Oncology Program
Grand Rapids, Michigan, United States, 49503
United States, Nebraska
Nebraska Methodist Cancer Center
Omaha, Nebraska, United States, 68114
United States, New Hampshire
Portsmouth Regional Hospital
Portsmouth, New Hampshire, United States, 03801
United States, Ohio
Oncology Hematology Care, Inc
Cincinnati, Ohio, United States, 45242
United States, Pennsylvania
Berks Hematology Oncology Associates
West Reading, Pennsylvania, United States, 19611
United States, Tennessee
Tennessee Oncology, PLLC
Nashville, Tennessee, United States, 37203
United States, Texas
The Center for Cancer and Blood Disorders
Fort Worth, Texas, United States, 76104
United States, Virginia
Peninsula Cancer Institute
Newport News, Virginia, United States, 23601
Sponsors and Collaborators
SCRI Development Innovations, LLC
Celgene Corporation
Study Chair: Denise A. Yardley, M.D. SCRI Development Innovations, LLC

Responsible Party: SCRI Development Innovations, LLC Identifier: NCT01033032     History of Changes
Other Study ID Numbers: SCRI BRE 161
First Posted: December 16, 2009    Key Record Dates
Results First Posted: January 6, 2015
Last Update Posted: January 6, 2015
Last Verified: December 2014

Keywords provided by SCRI Development Innovations, LLC:
Metastatic Breast Cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antineoplastic Agents