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

Summary

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.

Conditions

• Metastatic Breast Cancer
• Breast Cancer
• Breast Neoplasms
• Stage IV Breast Cancer
• Metastatic Cancer
• Invasive Ductal Carcinoma of Female Breast
• Invasive Ductal Breast Cancer
• Adenocarcinoma Breast

Interventions

DRUG

LTLD

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.

PROCEDURE

MR-HIFU induced hyperthermia

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.

DRUG

Cyclophosphamide

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.

Sponsors & Collaborators

• Dutch Cancer Society

  collaborator OTHER

• Center for Translational Molecular Medicine

  collaborator OTHER

• Vrienden UMC Utrecht

  collaborator UNKNOWN

• UMC Utrecht

  lead OTHER

Principal Investigators

• Britt BM Suelmann, MD · UMC Utrecht

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-03-31

Primary Completion

2022-11-30

Completion

2022-11-30

FDA Drug

Yes

Countries

• Netherlands

Study Locations