Temperature-Sensitive Liposomal Doxorubicin and Hyperthermia in Treating Women With Locally Recurrent Breast Cancer

Sponsor

Duke University (Other)

Overall Status

Terminated

CT.gov ID

NCT00346229

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

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

OBJECTIVES:

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.

Study Design

Study Type:

Interventional

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 :

Apr 1, 2006

Actual Primary Completion Date :

Apr 1, 2011

Actual Study Completion Date :

Apr 1, 2011

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose of temperature-sensitive liposomal doxorubicin (ThermoDox™) in combination with hyperthermia [4 years]

Secondary Outcome Measures

Pharmacokinetics [4 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

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

PATIENT CHARACTERISTICS:

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

PRIOR CONCURRENT THERAPY:

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