Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Carcinoma

Carcinoma in Situ

Carcinoma, Ductal

Carcinoma, Intraductal, Noninfiltrating

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Breast Neoplasms

Breast Carcinoma In Situ

Treatment technique used to deliver a highly focused and accurate radiation dose to a defined target volume outside the brain; the entire course of therapy delivered in five fractions or less

stereotactic body radiation therapy

Mark Perman, MD

Debra Freeman, MD

This is a multi-institutional, prospective, observational registry investigating the safety and efficacy of Accelerated Partial Breast Irradiation (APBI) using a Stereotactic Body Radiation Therapy (SBRT) delivery technique that incorporates real-time image guidance, noncoplanar fields, and respiratory tracking. The study will accrue 200 patients who will be treated to a dose of 30 Gy over the course of 5 fractions. These subjects will then have a follow up time of 5 years

RADIATION TREATMENT GUIDELINES and DOSIMETRY Fiducial Placement Prior to enrollment, patients will undergo breast conservation surgery preferably with fiducial markers implanted at the time of surgery or under ultrasonic guidance25

Patients treated with gantry-based SBRT preferably will have fiducials placed at the time of surgery.

For patients being treated with CyberKnife SBRT, four gold markers will be placed intraoperatively or ultrasonically to define the superior, inferior, medial, and lateral boundaries of the lumpectomy cavity in accordance with the manufacturer's (Accuray) documentation. At least three fiducials will be required for target tracking purposes to allow for rotational changes.

Simulation Linear Accelerator SBRT For treatments on a gantry-based linear accelerator, patients will be positioned supine with the arms elevated. CT scans will be obtained with 1.25 mm thickness and will be acquired with free breathing as well as additional scans as needed for motion control or gating. 4DCT, MRI and PET imaging may be used to assist in determining motion estimation.

CyberKnife SBRT For treatment on a robotic system, a contrast enhanced CT simulation is to be performed with 1 mm slices with the patient's arms at her sides in the supine position. The scan is to be performed with end-inspiratory breath hold from the thyroid to below the lungs. Breast immobilization devices including a vacuum mattress and a bra system will be allowed however bolus should not be used. Fiducial tracking (Synchrony) is to be used for motion tracking.

DOSIMETRY Target and Organs at Risk (OAR) contours

The following structures are to be contoured in all patients:

Tumor cavity (GTV) as defined on CT including all fiducials implanted on CT images Clinical Target Volume (CTV) defined as the tumor cavity expanded by a uniform 15 mm margin. The CTV will not extend beyond the skin, breast or chestwall Planning Tumor Volume (PTV) for SBRT will be defined as the CTV plus 3 - 5 mm as needed at the treating physician's discretion. PTV will be limited to GTV plus 20 mm margin Skin is defined as \<5 mm inside the external contour Chest wall includes the ribs and intercoastal musculature but does not include the pectoralis Heart contour begins below the level of where the pulmonary trunk branches into the left and right pulmonary arteries Lungs are to be contoured separately Spinal canal Breasts are to be contoured separately Dose Prescription The total prescribed dose to the PTV is 30 Gy delivered in 5 equal fractions of 6 Gy per day delivered on alternating days over 5 -10 total days. The prescribed dose must cover at least 95% of the PTV.

Accelerated Partial Breast Irradiation (APBI) Using Stereotactic Body Radiation Therapy (SBRT)

Accelerated Partial Breast Irradiation (APBI) Using Stereotactic Body Radiation Therapy (SBRT): a Multicenter, Observational Clinical Trial

physician and patient assessment of breast cosmetic result following SBRT

assessment of skin and breast tissue changes during and immediately following SBRT

assessment of pulmonary, cardiac and chest wall changes following SBRT

CyberKnife Coalition

RPCR, Inc.

Symptoms and General Pathology

Wounds and Injuries

Behaviors and Mental Disorders

Neoplasm Metastasis

Hyperthermia

Fever

Carcinoma, Ductal, Breast

Breast Diseases

Skin Diseases

Body Temperature Changes

Stress Disorders, Traumatic

Heat Stress Disorders

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Anti-Infective Agents

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

LTLD in combination with MR-HIFU induced hyperthermia and cyclophosphamide

Single arm study

Patients will receive up to six cycles at three-weeks intervals of:

* Intravenous LTLD dosed at 50mg/m2 administered during the MR-HIFU treatment
* 60 minutes of MR-HIFU mild local hyperthermia at 40 °C - 42 °C to the primary breast tumour
* Intravenous Cyclophosphamide 600 mg/m2 after MR-HIFU treatment

In case of toxicity, LTLD, cyclophosphamide and/or hyperthermia dosages will be adjusted as specified in the study protocol.

LTLD

Patients will receive up to six cycles at three-weeks intervals of:

- 60 minutes of MR-HIFU mild local hyperthermia at 40 °C - 42 °C to the primary breast tumour.

In case of toxicity, hyperthermia dosages will be adjusted as specified in the study protocol.

MR-HIFU induced hyperthermia

Patients will receive up to six cycles at three-weeks intervals of:

- Intravenous Cyclophosphamide 600 mg/m2 after MR-HIFU treatment

In case of toxicity, cyclophosphamide dosages will be adjusted as specified in the study protocol.

Mirjam A de Visser, MD

Britt BM Suelmann, MD

In this phase I feasibility study, the investigators evaluate the combination of lyso-thermosensitive liposomal doxorubicin (LTLD, ThermoDox) with local hyperthermia and cyclophosphamide (C), for the local treatment of the primary breast tumour in patients with metastatic breast cancer.

When heated to 40-43 degrees Celsius (ºC), LTLD releases a very high concentration of doxorubicin locally within seconds. Hyperthermia of the primary tumour will be induced by Magnetic Resonance guided High Intensity Focused Ultrasound (MR-HIFU) on a dedicated Sonalleve MR-HIFU breast system.

The investigators hypothesize that by substituting doxorubicin (A) in the AC-chemotherapy regimen for the combination of LTLD and MR-HIFU induced hyperthermia, optimal local tumour control can be achieved without compromising systemic toxicity or efficacy.

This will be the first study to evaluate LTLD with MR-HIFU hyperthermia in breast cancer patients.

Advances in systemic treatment led to improved overall survival in patients with metastatic breast cancer. Various studies suggest that by obtaining loco-regional control, overall survival in advanced disease can further be improved.

Pre-operative chemotherapy can be used in metastatic breast cancer to make radical removal of the primary tumor feasible, while simultaneously maintaining control of already present metastatic sites. The doxorubicin and cyclophosphamide regimen (AC) is well-known both in (neo-)adjuvant setting as in treatment of metastatic breast cancer. At present, optimal local control in advanced breast cancer using adequate dosing of doxorubicin is hampered by its toxic systemic effects. Therefore the investigators aim to increase doxorubicin deposition in the primary tumor without interfering with systemic efficacy and toxicity, by combining lyso-thermosensitive liposomal doxorubicin (LTLD, ThermoDox) with local mild hyperthermia, induced by Magnetic Resonance guided High Intensity Focused Ultrasound (MR-HIFU). When heated to 40-43 ºC, ThermoDox releases a very high concentration of doxorubicin locally within seconds. In the absence of hyperthermia, ThermoDox leads to a similar biodistribution and antitumor efficacy to free doxorubicin. MR-HIFU allows for controlled heating of deep-seated tumors.

This is a single-arm phase I feasibility study in 12 patients with de novo stage IV (distant metastasis at the time of diagnosis) her2-negative breast cancer, who have not received previous chemotherapy. The study treatment consists of up to 6 cycles at 21-day intervals of ThermoDox (50mg/m2) administered during MR-HIFU induced hyperthermia (60 minutes at 40-42 ᵒC) and cyclophosphamide (600 mg/m2) administered afterwards. A dedicated MR-HIFU breast system integrated with a clinical 1.5 Tesla Magnetic Resonance Imaging (MRI) scanner will be used for safe and controlled heating of the tumour. Primary endpoints are safety, tolerability and feasibility. Secondary endpoint is efficacy, assessed by radiological response of the local tumor and the distant metastases.

In the Biobank side study, extra blood samples will be collected. These samples will be used for further research on not yet determined topics related to breast cancer.

Image-guided Targeted Doxorubicin Delivery With Hyperthermia to Optimize Loco-regional Control in Breast Cancer

Image-guided Targeted Doxorubicin Delivery With Hyperthermia to Optimize Loco-regional Control in Breast Cancer. Phase I Feasibility Study of Hifu-Induced Hyperthermia, LTLD and Cyclophosphamide for Metastatic Breast Cancer

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Accelerated Partial Breast Irradiation (APBI) Using Stereotactic Body Radiation Therapy (SBRT)	NCT04985032	Ductal Carcinom... Invasive Ductal...	stereotactic bo...	50 Years - 100 Years	RPCR, Inc.
Image-guided Targeted Doxorubicin Delivery With Hyperthermia to Optimize Loco-regional Control in Breast Cancer	NCT03749850	Metastatic Brea... Breast Cancer Breast Neoplasm... Stage IV Breast... Metastatic Canc... Invasive Ductal... Invasive Ductal... Adenocarcinoma ...	LTLD MR-HIFU induced... Cyclophosphamid...	18 Years -	UMC Utrecht
Image-guided Targeted Doxorubicin Delivery With Hyperthermia to Optimize Loco-regional Control in Breast Cancer	NCT03749850	Metastatic Brea... Breast Cancer Breast Neoplasm... Stage IV Breast... Metastatic Canc... Invasive Ductal... Invasive Ductal... Adenocarcinoma ...	LTLD MR-HIFU induced... Cyclophosphamid...	18 Years -	UMC Utrecht

Spots Global Cancer Trial Database for invasive ductal carcinoma of female breast