Phase 1/2 Study of ThermoDox With Approved Hyperthermia in Treatment of Breast Cancer Recurrence at the Chest Wall

Inclusion Criteria:

1. Histologically documented recurrent/metastatic adenocarcinoma of the breast with a recurrence on the chest wall (or its overlying skin):

   * Subjects with ulcerative chest wall disease defined as non-healing wounds consistent with cancer are eligible.
   * Subjects with prior skin changes consistent with inflammatory breast carcinoma are eligible.
   * Breast carcinoma for medical reasons not being resected
2. Tumor thickness must be clinically indicated for hyperthermia therapy, as measured by clinical exam or imaging studies (CT or MRI). The target local tumor lesion(s) must be able to be covered within two hyperthermia fields of treatment.
3. Disease that has progressed despite other available standard treatment options, based on what is clinically indicated according to the investigator's clinical and medical judgment, including:

   * One or more radiation treatment(s) to the chest wall or breast up to a maximum prior dose of 12,000 cGy in the hyperthermia field (not administered less than 28 days prior to enrollment).
4. Subjects who have previously received hyperthermia in conjunction with either radiation therapy or chemotherapy are eligible.
5. Subjects may have distant metastasis, including brain metastases. Subjects with known brain metastases are eligible if:

   * They have received standard anti-tumor treatment for their brain metastases without encephalopathy;
   * Their neurological function is stable for at least 30 days and either off steroid therapy or on a stable steroid regimen.
6. Non-pregnant female at least 18 years of age. If the subject is of child-bearing age, must have a negative serum pregnancy test at baseline and must agree to practice an acceptable form of birth control while on the study.
7. Provide written informed consent and willing to comply with protocol requirements.

Exclusion Criteria:

1. Requires any concomitant antineoplastic therapy. Prior chemotherapy should not be administered within 5 half-lives or 28 days whichever is shorter. Subjects on a current stable dose of hormonal treatments may continue on a stable dose during the study (i.e. arimidex, amarosin, herceptin).
2. Prior confirmed allergic reaction (including moderate rash, dyspnea, wheezing, urticaria or other symptoms) attributed to the administration of either anthracyclines or other liposomally encapsulated drugs that required discontinuation of prior therapy.
3. Prior therapy with anthracyclines exceeding the following doses (subjects will be discontinued at 600 mg/m2 lifetime dose irrespective of the number of ThermoDox® cycles received):

   Free (i.e., non-liposomal) or liposomal doxorubicin \> 450 mg/m2 Free epirubicin \> 900 mg/m2.
4. Previous (required active treatment within 5 years) or concomitant malignancy except basal cell cancer, in situ carcinoma of the cervix, or contralateral breast cancer. Subjects with a prior contralateral breast malignancy can be included if they did not receive any chemotherapy.
5. Baseline laboratories (repeat labs can be evaluated at baseline to establish eligibility):

   * ANC Granulocytes \< 1,500/ microliter
   * Platelets \< 75,000/ microliter
   * Hemoglobin \< 9 gm/dL
   * Total Bilirubin \> 2 mg/dL
   * ALT and AST \> 2.5 X upper limit of normal
   * Creatinine \> 1.5 X upper limit of normal.
6. ECOG/Zubrod Performance Status \> 2.
7. MUGA/Echocardiogram Left Ventricular Ejection Fraction \< 50%.
8. Has a medical or psychiatric condition or other circumstances which would significantly decrease the chances of obtaining reliable data, achieving study objectives, or completing the study and/or post-dose follow-up examinations.
9. History of:

   * Acute coronary syndrome
   * Cerebral vascular accident
   * Abnormal cardiac stress testing within last 6 months
   * Symptomatic coronary artery disease
   * Uncontrolled hypertension or cardiomyopathy
   * Cardiac valvular surgery or open heart surgery
   * Known structural heart disease.
10. Has a condition which may interfere with the hyperthermia portion of the trial such as: functioning cardiac pacemaker; metal plates, rods or prosthesis of the chest wall, breast reconstruction with implants, severe numbness and/or tingling of the chest wall or breast, skin grafts and/or flaps on the breast or chest wall.
11. Active infection requiring antibiotic treatment
12. Has received any external radiation therapy within 28 days prior to enrollment.