Image-guided targeted doxorubicin delivery with hyperthermia to optimize loco-regional control in breast cancer; the i-GO feasibility study. Phase I Feasibility Study of High-Intensity Focused Ultrasound-Induced Hyperthermia, Lyso-Thermosensitive Liposomal Doxotubicin for Metastatic Breast Cancer

Recruitment & Eligibility

Status: Pending

Sex: Not specified

Target Recruitment: 12

Inclusion Criteria

Patients must meet all of the following inclusion criteria:
1. Histologically confirmed adenocarcinoma of the breast and planned for
palliative chemotherapy with doxorubicine monotherapy or combination therapy
with cyclophosphamide
2. Biopsy-proven stage T1-4c2AnyNM1 at the diagnosis of breast cancer.
3. Non-pregnant, non-lactating female at least 18 years of age. If patient is
child-bearing age, she must have a negative serum pregnancy test prior to
enrollment and must agree to practice an acceptable form of birth control while
on study.
4. The tumor is located within the reach of the HIFU beam (based on
pre-treatment DCE-MRI findings).
5. The target breast is expected to fit in the cup of the dedicated MR-HIFU
breast system (based on pre-treatment MRI findings).
6. The patient weighs less than 90 kg (restrictment of the HIFU table top).
7. Provide written informed consent and willing to comply with protocol
requirements.

Exclusion Criteria

Patients will be excluded if any of the following conditions are observed:
1. HER2-positive disease or classic invasive lobular carcinoma (ILC).
2. A treatment plan with curative intent is available.
3. Progression under prior therapy with antracyclines or other indications that
anthracycline-resistance may be present
4. Prior treatment with anthracyclines exceeding a maximum dose of 240 mg/m2
5. No measurable disease at baseline (according to RECIST 1.1 or PERCIST 1.0)
6. Any concomitant malignancy
7. Prior sensitivity (including rash, dyspnea, wheezing, urticarial, or other
symptoms) attributed to any liposomal-encapsulated drug.
8. Baseline laboratory valuesies:
ANC**************. < 1.5 x 10^9/L
Platelets ************... < 75 x 10^9/L
Hemoglobin ***********. < 5.6 mmol/L (9 g/dl)
Total Bilirubin **********. > 1.5X upper limit of normal
(in our hospital >32 µmol/L)
ALAT and ASAT **********. > 2.5X upper limit of normal (in our hospital >88U/L
and >75U/L respectively)
> 5X upper limit of normal in case of liver metastases
eGFR < 30 ml/min/1.73m2
9. World Health Organization Performance Status (WHO-PS) >2.
10. Left Ventricular Ejection Fraction <50% (validated by baseline scan).
11. History of:
a. Acute coronary syndrome in the last year
b. Cerebral vascular accident in the last year
c. Abnormal cardiac stress testing within last 6 months
d. Symptomatic coronary artery disease
e. Uncontrolled hypertension or cardiomyopathy
f. Cardiac valvular surgery or open heart surgery in the last year
g. Known structural heart disease
12. Any 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 prosthesis in the treated breast, severe numbness
and/or tingling of the chest wall or breast, skin grafts and/or flaps on the
breast or chest wall, scar tissue or surgical clips in the HIFU beam path.
13. Active infection
14. Body temperature > 38.0 degrees Celsius on the day of a MR-HIFU treatment.
15. Concurrent use of any of the following prohibited medications within a
reasonable wash-out time: protease inhibitors, cyclosporine, carbamazepine,
phenytoin, valproic acid, paclitaxel, trastuzumab and other liposomal drugs
(AbelectTM, Ambisome*, NyotranTM, etc.) or lipid-complexed drugs.
16. Caution will be exercised with all the medications mentioned in appendix C
of the study protocol, for interactions are theoretically possible.
17. Contraindications to MR imaging (e.g., pacemaker in situ, severe
claustrophobia, metal implants incompatible with the MRI-scan, body size
incompatible with MR bore).
18. Contraindications to gadolinium-based contrast agent and the tumor is not
sufficiently visible on MRI without contrast (including prior allergic reaction
to gadolinium-based contrast agent, and/or renal failure).
19. Contraindications to sedation and analgesia with propofol and Remifentanil,
including history of Chronic Obstructive Pulmonary Disease (COPD) that results
in the inability to perform a physical activity corresponding with a Metabolic
Equivalent (MET) of 4; dependence on artificial ventilation at home; sleep
apnea or an American Society of Anesthesiologists (ASA) classificiation >=4.
20. Inability to lie in prone position.
21. A medical or psychiatr

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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