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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier:
NCT01033032
First received: December 15, 2009
Last updated: July 17, 2014
Last verified: July 2014
  Purpose

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 Intervention Phase
Metastatic Breast Cancer
Drug: Amrubicin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by SCRI Development Innovations, LLC:

Primary Outcome Measures:
  • Phase I: Evaluate the maximum tolerated dose (MTD) and tolerability of amrubicin monotherapy in HER2-negative metastatic breast cancer [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
  • Phase II: Assess progression-free survival (PFS) of patients with HER2-negative metastatic breast cancer treated with single-agent amrubicin as second- or third-line therapy. (Phase II will use the amrubicin dose determined in Phase I). [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Determine toxicity (including cardiotoxicity) of amrubicin when given as second- or third-line treatment for HER2-negative metastatic breast cancer. [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
  • Determine overall survival (OS) of patients with HER2-negative metastatic breast cancer who receive amrubicin as second- or third-line metastatic breast cancer treatment. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Determine response rate (RR) of patients with HER2-negative metastatic breast cancer who receive amrubicin as second- or third-line metastatic breast cancer treatment [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Enrollment: 77
Study Start Date: December 2009
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Amrubicin
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 Names:
  • Systemic therapy
  • Amrubicin

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01033032

Locations
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
National Capital Clinical Research Consortium
Bethesda, Maryland, United States, 20817
Center for Cancer and Blood Disorders
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
Investigators
Study Chair: Denise A. Yardley, M.D. SCRI Development Innovations, LLC
  More Information

No publications provided

Responsible Party: SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier: NCT01033032     History of Changes
Other Study ID Numbers: SCRI BRE 161
Study First Received: December 15, 2009
Last Updated: July 17, 2014
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Amrubicin
Antineoplastic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014