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Temperature-Sensitive Liposomal Doxorubicin and Hyperthermia in Treating Women With Locally Recurrent 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: NCT00346229
Recruitment Status : Terminated (Funding)
First Posted : June 29, 2006
Last Update Posted : March 22, 2016
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Duke University

Brief Summary:

RATIONALE: Drugs used in chemotherapy, such as liposomal doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Hyperthermia therapy kills tumor cells by heating them to several degrees above normal body temperature. Giving temperature-sensitive liposomal doxorubicin together with hyperthermia may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of temperature-sensitive liposomal doxorubicin when given together with hyperthermia in treating women with locally recurrent breast cancer.

Condition or disease Intervention/treatment Phase
Breast Cancer Biological: filgrastim Biological: pegfilgrastim Drug: lyso-thermosensitive liposomal doxorubicin(Thermodox) Procedure: hyperthermia treatment Phase 1

Detailed Description:


  • Determine the maximum tolerated dose of temperature-sensitive liposomal doxorubicin (ThermoDox™) when used in combination with local-regional hyperthermia in women with locally recurrent breast cancer.
  • Determine the pharmacokinetic profile of ThermoDox™ when used in multiple-course dosing.

OUTLINE: This is a dose-escalation study of temperature-sensitive liposomal doxorubicin (ThermoDox™).

Patients receive ThermoDox™ IV over 30 minutes immediately followed by hyperthermia to the chest wall/axilla over 1-2 hours on day 1. Treatment repeats every 21-35 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of ThermoDox™ (with or without standard-dose granulocyte colony-stimulating factor [G-CSF] support) until the maximum tolerated dose (MTD) is determined. The MTD without G-CSF support is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity (DLT). At least 6 patients are treated at the MTD. If the only DLT is neutropenia in > 1 of 6 patients treated at any dose level, then additional cohorts of 3-6 patients receive escalating doses of ThermoDox™ with G-CSF support (standard-dose G-CSF or standard-dose pegfilgrastim) until the MTD is determined. The MTD with G-CSF support is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience DLT after the addition of G-CSF support.

Quality of life and pain are assessed at baseline, prior to courses 3 and 5, and at 21-42 days after completion of therapy.

After completion of study treatment, patients are followed periodically for 5 years.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 29 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I, Dose Escalation and Pharmacokinetics Study of Temperature Sensitive Liposome Encapsulated Doxorubicin (ThermoDox™) and Hyperthermia in Patients With Local-Regionally Recurrent Breast Cancer
Study Start Date : April 2006
Actual Primary Completion Date : April 2011
Actual Study Completion Date : April 2011

Arm Intervention/treatment
Experimental: Thermodox
ThermoDox20-40mg/m2 every 21-35 days followed by Chest Wall Hyperthermia
Biological: filgrastim
Biological: pegfilgrastim
Drug: lyso-thermosensitive liposomal doxorubicin(Thermodox)
Procedure: hyperthermia treatment

Primary Outcome Measures :
  1. Maximum tolerated dose of temperature-sensitive liposomal doxorubicin (ThermoDox™) in combination with hyperthermia [ Time Frame: 4 years ]

Secondary Outcome Measures :
  1. Pharmacokinetics [ Time Frame: 4 years ]

Information from the National Library of Medicine

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


  • Histologically confirmed adenocarcinoma of the breast

    • Locally recurrent disease involving the chest wall and/or its overlying skin

      • Clinically and biopsy proven disease on the chest wall area measuring ≥ 1 cm
      • Overall surface extent of tumor ≤ two 16 x 16 cm fields
      • Tumor thickness ≤ 3 cm by clinical exam and CT scan or MRI
      • Disease extent on the chest wall that exceeds the above criteria allowed provided no other local therapies are available
      • Patients with axillary disease involvement only must meet the above criteria in order to be eligible
      • Prior skin changes consistent with inflammatory breast cancer are allowed
  • Distant metastasis (excluding known brain metastases) allowed

    • No resectable chest wall recurrence as the only site of metastatic disease
    • No refractory pain secondary to metastatic disease
  • Must have undergone prior local radiotherapy to the chest wall or breast in the adjuvant or metastatic setting
  • Must have progressed on ≥ 1 course of hormonal therapy for metastatic disease (if tumor is estrogen receptor positive or progesterone receptor positive) AND ≥ 1 course of chemotherapy
  • Prior contralateral breast malignancy allowed provided not previously treated with chemotherapy
  • Hormone receptor status not specified


  • Female
  • Menopausal status not specified
  • Zubrod performance status 0-1 OR Karnofsky performance status 90-100%
  • Not pregnant
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Granulocyte count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 9 g/dL
  • Bilirubin normal
  • alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times upper limit of normal (ULN)
  • Creatinine ≤ 1.5 times ULN
  • left ventricular ejection fraction (LVEF) ≥ 50% by multiple gated acquisition scan (MUGA) or echocardiogram
  • No nonhealing wounds or active infection in the area of the chest wall
  • No clinically significant findings on baseline evaluations, including laboratory and physical examinations, vital signs, and ECG
  • No prior sensitivity (e.g., rash, dyspnea, wheezing, urticaria, or other symptoms) attributed to anthracyclines or other liposomally encapsulated drugs
  • No other prior or concurrent primary malignancy except for melanoma in situ, nonmelanoma skin cancer, squamous cell carcinoma, or noninvasive cervical carcinoma
  • No history of any of the following:

    • Cardiac ischemia or acute coronary artery syndrome, myocardial infarction (MI), cerebral vascular accident, or abnormal cardiac stress testing within the last 6 months
    • Coronary artery disease (including non-Q wave MI)
    • Uncontrolled hypertension or cardiomyopathy
    • Cardiac valvular surgery or open heart surgery
    • Known structural heart disease
  • No other serious medical illness including, but not limited to, the following:

    • Congestive heart failure
    • Life-threatening cardiac arrhythmias
    • Acute or chronic liver disease
  • No major psychiatric illness that required inpatient treatment within the past 3 months or that would preclude obtaining informed consent
  • No concurrent devices or conditions that might interfere with the hyperthermia portion of the trial, including any of the following:

    • Functioning cardiac pacemaker
    • Metal plates, rods, or prosthesis of the chest wall
    • Severe numbness and/or tingling of the chest wall or breast
    • Skin grafts and/or flaps on the breast or chest wall
    • Unstable cardiovascular or pulmonary status
  • No known allergy to eggs or egg products


  • See Disease Characteristics
  • More than 3 months since prior major surgery
  • No prior therapy with anthracyclines exceeding the following doses:

    • Doxorubicin hydrochloride > 450 mg/m^2
    • Epirubicin hydrochloride > 900 mg/m^2
  • More than 42 days since prior trastuzumab (Herceptin®)
  • More than 90 days since prior radiotherapy to the involved chest wall area
  • No other concurrent systemic anticancer therapy, including hormonal therapy, chemotherapy, or investigational anticancer therapy
  • No concurrent radiotherapy, including radiotherapy for pain control
  • No concurrent administration of any of the following drugs:

    • Amphotericin B by injection
    • Antithyroid agents
    • Azathioprine
    • Chloramphenicol
    • Colchicine
    • Flucytosine
    • Ganciclovir
    • Interferon
    • Plicamycin
    • Zidovudine
    • Sulfinpyrazone
    • Probenecid
    • Cyclosporine
    • Phenobarbital
    • Phenytoin
    • Streptozocin
    • Live vaccines
  • Concurrent bisphosphonates for palliation of bony metastasis allowed

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): NCT00346229

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United States, North Carolina
Duke Cancer Institute
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Duke University
National Cancer Institute (NCI)
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Principal Investigator: Kimberly L. Blackwell, MD Duke Cancer Institute
Publications of Results:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Duke University Identifier: NCT00346229    
Other Study ID Numbers: Pro00014340
CDR0000482411 ( Other Identifier: Secondary ID )
First Posted: June 29, 2006    Key Record Dates
Last Update Posted: March 22, 2016
Last Verified: October 2013
Keywords provided by Duke University:
stage III B breast cancer
stage III C breast cancer
stage IV breast cancer
inflammatory breast cancer
recurrent breast cancer
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Body Temperature Changes
Signs and Symptoms
Liposomal doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action