Phase 1/2 Study of ThermoDox With Approved Hyperthermia in Treatment of Breast Cancer Recurrence at the Chest Wall (DIGNITY)
This study has been completed.
Information provided by (Responsible Party):
First received: January 19, 2009
Last updated: November 14, 2016
Last verified: November 2016
This is a research study to evaluate the effects of ThermoDox in combination with therapeutic heating of the chest wall in the treatment of recurrent regional breast cancer. The purpose of this study is to evaluate the bioequivalence of ThermoDox and measure efficacy in recurrent chest wall patients.
Drug: ThermoDox in combination with Microwave Hyperthermia (heat)
||Endpoint Classification: Bio-equivalence Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||A Phase I/II Study Evaluating the Maximum Tolerated Dose, Bioequivalence/Pharmacokinetics, Safety, and Efficacy of Hyperthermia and ThermoDox (Lyso-Thermosensitive Liposomal Doxorubucin) in Patients With Local-Regional Recurrent Breast Cancer.
Primary Outcome Measures:
- To determine the bioequivalence of ThermoDox when used with hyperthermia among patients with RCW breast cancer. [ Time Frame: PK collection at Cycle 1 and Cycle 2 ] [ Designated as safety issue: No ]
- To determine efficacy of ThermoDox in combination with Hyperthermia [ Time Frame: Efficacy assessed at Cycle 3, Cycle 5 and End of Treatment ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- To evaluate the safety of ThermoDox in combination with Hyperthermia [ Time Frame: Through 6 treatment Cycles ] [ Designated as safety issue: Yes ]
| Study Start Date:
| Study Completion Date:
| Primary Completion Date:
||December 2015 (Final data collection date for primary outcome measure)
Experimental: Thermodox in combination with hyperthermia
Single arm study
Drug: ThermoDox in combination with Microwave Hyperthermia (heat)
ThermoDox is a 30 minute intravenous infusion followed by hyperthermia within 60 minutes of infusion completion.
Hyperthermia is a therapy used to heat tumors for 60 minutes. Using heat energy, the tumor is heated to a certain temperature. The heat can damage cancer cells at levels that are usually safe for normal cells and can be used to attack cancer in four major ways: 1) heat damages or weakens the cells of the tumor; 2) heat increase blood flow through the weakened tumor; 3) increased blood flow raises oxygen levels in tumors; and 4) when the body senses fever it can stimulate the nature immune system.
All patients will receive up to six ThermoDox/hyperthermia treatments at 21-day intervals.
|Ages Eligible for Study:
||18 Years and older (Adult, Senior)
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
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
- 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.
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).
- Subjects who have previously received hyperthermia in conjunction with either radiation therapy or chemotherapy are eligible.
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.
- 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.
- Provide written informed consent and willing to comply with protocol requirements.
- 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).
- 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.
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.
- 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.
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.
- ECOG/Zubrod Performance Status > 2.
- MUGA/Echocardiogram Left Ventricular Ejection Fraction < 50%.
- 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.
- 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.
- 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.
- Active infection requiring antibiotic treatment
- Has received any external radiation therapy within 28 days prior to enrollment.
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: NCT00826085
|University of California, San Francisco
|San Francisco, California, United States, 94143 |
|Southeastern Regional Medical Center
|Newnan, Georgia, United States, 30265 |
|University of Maryland
|Baltimore, Maryland, United States, 21201 |
|Washington University in St. Louis
|St. Louis, Missouri, United States, 63110 |
|Southwestern Regional Medical Center
|Tulsa, Oklahoma, United States, 74133 |
|Eastern Regional Medical Center
|Philadelphia, Pennsylvania, United States, 19124 |
||Nicholas Borys, MD
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Zagar TM, Vujaskovic Z, Formenti S, Rugo H, Muggia F, O'Connor B, Myerson R, Stauffer P, Hsu IC, Diederich C, Straube W, Boss MK, Boico A, Craciunescu O, Maccarini P, Needham D, Borys N, Blackwell KL, Dewhirst MW. Two phase I dose-escalation/pharmacokinetics studies of low temperature liposomal doxorubicin (LTLD) and mild local hyperthermia in heavily pretreated patients with local regionally recurrent breast cancer. Int J Hyperthermia. 2014 Aug;30(5):285-94. doi: 10.3109/02656736.2014.936049.
History of Changes
|Other Study ID Numbers:
|Study First Received:
||January 19, 2009
||November 14, 2016
||United States: Food and Drug Administration
Keywords provided by Celsion:
Recurrent Chest Wall Cancer
Loco-regional Recurrent Breast Cancer
Breast Cancer Recurrence at the Chest Wall
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on December 02, 2016
Neoplasms by Site
Body Temperature Changes
Signs and Symptoms