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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

Phase 1
18 Years
Not Enrolling
Breast Cancer

Thank you

Trial Information

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


- 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

OUTLINE: This is a dose-escalation study of temperature-sensitive liposomal doxorubicin

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.

Inclusion Criteria


- 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

- 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

- 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

- 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

Type of Study:


Study Design:

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose of temperature-sensitive liposomal doxorubicin (ThermoDox™) in combination with hyperthermia

Outcome Time Frame:

4 years

Safety Issue:


Principal Investigator

Kimberly L. Blackwell, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Duke Cancer Institute


United States: Food and Drug Administration

Study ID:




Start Date:

April 2006

Completion Date:

April 2011

Related Keywords:

  • Breast Cancer
  • stage III B breast cancer
  • stage III C breast cancer
  • stage IV breast cancer
  • inflammatory breast cancer
  • recurrent breast cancer
  • Breast Neoplasms
  • Fever



Duke Cancer Institute Durham, North Carolina  27710