Breast CancerPhase 1USmBRT-BNCT04431674
Novel MRI-Guided Ultrasound Stimulated Microbubble Radiation Treatment for Patients With Chest-wall and Breast Cancer
A Phase 1 study testing Definity Suspension for Injection in people with Breast Cancer, run by Sunnybrook Health Sciences Centre at 1 site in Canada.
Trial summary
The objective of this study is to demonstrate the feasibility of novel MRI-guided ultrasound stimulated microbubble treatment to enhance radiation effects in humans receiving external beam radiotherapy delivered using a LINAC (linear accelerator) radiation therapy device. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Definity Suspension for Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteCanada
- Study dates
- 22 Jul 2020to 21 Jun 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years
- All biopsy-confirmed invasive ductal, invasive lobular and other rare histologic types of carcinoma
- Patients with early stage Breast cancer, or LABC ; i.e., Stage IIA - IIIC cancers (T2 N0 M0 to Any T, N3, M0) or Stage IV (Any T, Any N, M1) per AJCC guidelines (8th Edition)
- Assessed by a multidisciplinary team of treating medical, surgical and radiation oncologist and found suitable for the treatment
- Patient referred for palliative radiotherapy or standard radiotherapy, which may include any of the following dose regimens: 1) 20 Gy in 5 fractions, 2) 30 Gy in 10 fractions, 3) 40 Gy in 10 fractions, 4) 50 Gy in 20 fractions, 5) 60 Gy in 30 fractions and 6) 66 Gy in 33 fractions.
- Able to understand and give informed consent
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- Weight < 140 kg
- Target lesion accessible for MRg-FU+MB procedure
- Able to communicate sensation during the procedure
- Creatinine within normal institutional limits or creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels above institutional upper limit of normal.
Who cannot join
- Pregnant or lactating women may not participate due to the embryotoxic effects of protocol treatment. Women/ men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
- Unable to have a contrast-enhanced MRI scan - standard of care criteria
- Patients on anthracycline or taxane based chemotherapy
- Patients with metallic or breast implants
- Subjects with inflammatory breast cancer, connective tissue disorder, musculoskeletal deformity
- Target lesion causing ulceration, bleeding or discharge of the overlying skin
Show all 19Show fewer
- A fibrotic scar along the proposed FU beam path
- Severe cardiovascular, neurological, renal or hematological chronic disease
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≥ 3
- Any condition in the investigator's opinion precludes participation
- Bleeding disorders/ High risk for deep vein thrombosis
- Unable to tolerate required stationary position during treatment
- Allergic to Definity microbubbles
- Cardiac disease or unstable hemodynamics including myocardial infarction within six months, unstable angina, congestive heart failure, ejection fraction < 50%, cardiac shunts, cardiac arrythmia and cardiac pacemaker.
- Contraindication to perflutren including subjects with a family or personal history of QT prolongation or taking concomitant medications known to cause QTc prolongation like cisapride, erythromycin, tricyclic antidepressants, Class IA and III antiarrhythmic agents and some antipsychotics like haloperidol, droperidol, quetiapine, thioridazine, ziprasidone.
- QT prolongation observed on screening ECG (QTc > 450ms for men or >470ms for women)
- Severe hypertension (diastolic BP > 100 mmHg)
- History of bleeding disorder, coagulopathy
- Severely impaired renal function with estimated glomerular filtration rate < 30ml/min/1.73m2 and/or on dialysis
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Novel Magnetic Resonance Imaging -Guided Ultrasound-Stimulated Microbubble Radiation Treatment for Patients With Chest-Wall and Locally Advanced Breast Cancer
The objective of this study is to demonstrate the feasibility of novel MRI-guided ultrasound stimulated microbubble treatment to enhance radiation effects in humans receiving external beam radiotherapy delivered using a LINAC (linear accelerator) radiation therapy device.
Read the detailed description
The objective of this study is to demonstrate the feasibility of novel MRI-guided ultrasound stimulated microbubble treatment to enhance radiation effects in humans receiving external beam radiotherapy delivered using a LINAC (linear accelerator) radiation therapy device. The investigators have previously demonstrated that ultrasound and microbubble mediated endothelial cell perturbation can significantly enhance the effectiveness of radiation. It enhances tumour response to radiation significantly by synergistically destroying tumour blood vessels. The technique is targeted spatially and achieves tumour specificity by confining the low-power ultrasonic fields that stimulate microbubbles to the tumour location only. By perturbing the tumour vasculature and activating specific genetic pathways, the technique sensitizes the targeted tissues to the subsequent therapeutic application of radiation, resulting in significantly enhanced cell killing. The primary aim of this research is to evaluate the safety profile of MRI-guided ultrasound stimulated microbubble treatment and radiation in patients with chest wall and breast cancer. The secondary aim is to evaluate tumor (primary and/or nodal) response to MRg-FU + MB and radiation, as measured radiologically within the treated therapeutic regions.
- Conditions
- Breast Cancer
- Being tested
- Definity Suspension for Injection
- Keywords
- Breast Cancer, Focused ultrasound, Microbubbles
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Definity Suspension for InjectionDrug
MRI-guided ultrasound-stimulated microbubble-treatment
| Study group | Role | What they receive |
|---|---|---|
| MRg-FUS MB Treatment | Experimental | Patients with locally advanced breast cancer (LABC) and chest wall tumours will receive MRI-guided ultrasound-stimulated microbubble-treatment combined with radiotherapy on a LINAC. Receives: Drug: Definity Suspension for Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of toxicity and adverse events using MRg-FUS+MB treatment in patients with chest-wall and locally advanced breast cancer
Incidence of toxicity and adverse events
Measured: 90 days
Secondary outcomes (1)
Radiological Response
The secondary endpoint is radiological response in breast cancer following MRg-FU + MB + radiation, after a 3 month follow up.
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2020
- Study start22 Jul 2020
- Primary completion21 Jun 2023
- Study completion21 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Sunnybrook Health Sciences CentreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Prospective, Single-Centre, Single-Arm, Non-Randomized, Phase-I MRI-Guided Ultrasound Stimulated Microbubbles Radiation Treatment for Patients with Chest Wall and Breast Cancer
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sunnybrook Health Sciences Centre
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Gregory Czarnota, Sunnybrook Health Sciences Centre
- Investigators
- Dr. Gregory Czarnota, MD, Principal investigator, Sunnybrook Health Sciences Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04431674
- Sponsor's protocol ID
- 077-2019
- Acronym
- USmBRT-B
- Status last verified
- Dec 2023
- First submitted
- 11 Jun 2020
- Last updated
- 13 Dec 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Moore-Palhares D, Dasgupta A, Saifuddin M, Anzola Pena ML, Prasla S, Ho L, Lu L, Kung J, McNabb E, Sannachi L, Vesprini D, Chen H, Karam I, Soliman H, Szumacher E, Chow E, Gandhi S, Trudeau M, Curpen B, Stanisz GJ, Kolios M, Czarnota GJ. Radiation enhancement using focussed ultrasound-stimulated microbubbles for breast cancer: A Phase 1 clinical trial. PLoS Med. 2024 May 17;21(5):e1004408. doi: 10.1371/journal.pmed.1004408. eCollection 2024 May.
PubMed 38758967Dasgupta A, Saifuddin M, McNabb E, Ho L, Lu L, Vesprini D, Karam I, Soliman H, Chow E, Gandhi S, Trudeau M, Tran W, Curpen B, Stanisz G, Sahgal A, Kolios M, Czarnota GJ. Novel MRI-guided focussed ultrasound stimulated microbubble radiation enhancement treatment for breast cancer. Sci Rep. 2023 Aug 21;13(1):13566. doi: 10.1038/s41598-023-40551-5.
PubMed 37604988
Study at a glance
From the registry record, last updated by the sponsor on 13 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Novel Magnetic Resonance Imaging -Guided Ultrasound-Stimulated Microbubble Radiation Treatment for Patients With Chest-Wall and Locally Advanced Breast Cancer
- ClinicalTrials.gov ID
- NCT04431674
- Acronym / sponsor ID
- USmBRT-B / 077-2019
- Conditions
- Breast Cancer
- Keywords
- Breast Cancer, Focused ultrasound, Microbubbles
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Sunnybrook Health Sciences CentreUniversity, hospital or other
- Study start
- 22 Jul 2020 (actual)
- Primary completion
- 21 Jun 2023 (actual)
- Study completion
- 21 Jun 2023 (actual)
- First posted
- 16 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of this study is to demonstrate the feasibility of novel MRI-guided ultrasound stimulated microbubble treatment to enhance radiation effects in humans receiving external beam radiotherapy delivered using a LINAC (linear accelerator) radiation therapy device.
Detailed description
The objective of this study is to demonstrate the feasibility of novel MRI-guided ultrasound stimulated microbubble treatment to enhance radiation effects in humans receiving external beam radiotherapy delivered using a LINAC (linear accelerator) radiation therapy device. The investigators have previously demonstrated that ultrasound and microbubble mediated endothelial cell perturbation can significantly enhance the effectiveness of radiation. It enhances tumour response to radiation significantly by synergistically destroying tumour blood vessels. The technique is targeted spatially and achieves tumour specificity by confining the low-power ultrasonic fields that stimulate microbubbles to the tumour location only. By perturbing the tumour vasculature and activating specific genetic pathways, the technique sensitizes the targeted tissues to the subsequent therapeutic application of radiation, resulting in significantly enhanced cell killing. The primary aim of this research is to evaluate the safety profile of MRI-guided ultrasound stimulated microbubble treatment and radiation in patients with chest wall and breast cancer. The secondary aim is to evaluate tumor (primary and/or nodal) response to MRg-FU + MB and radiation, as measured radiologically within the treated therapeutic regions.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Prospective, Single-Centre, Single-Arm, Non-Randomized, Phase-I MRI-Guided Ultrasound Stimulated Microbubbles Radiation Treatment for Patients with Chest Wall and Breast Cancer
| Arm | Type | Receives |
|---|---|---|
| MRg-FUS MB Treatment | Experimental | Drug: Definity Suspension for InjectionPatients with locally advanced breast cancer (LABC) and chest wall tumours will receive MRI-guided ultrasound-stimulated microbubble-treatment combined with radiotherapy on a LINAC. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Age ≥ 18 years
- All biopsy-confirmed invasive ductal, invasive lobular and other rare histologic types of carcinoma
- Patients with early stage Breast cancer, or LABC ; i.e., Stage IIA - IIIC cancers (T2 N0 M0 to Any T, N3, M0) or Stage IV (Any T, Any N, M1) per AJCC guidelines (8th Edition)
- Assessed by a multidisciplinary team of treating medical, surgical and radiation oncologist and found suitable for the treatment
- Patient referred for palliative radiotherapy or standard radiotherapy, which may include any of the following dose regimens: 1) 20 Gy in 5 fractions, 2) 30 Gy in 10 fractions, 3) 40 Gy in 10 fractions, 4) 50 Gy in 20 fractions, 5) 60 Gy in 30 fractions and 6) 66 Gy in 33 fractions.
Key exclusion criteria (19 listed)
- Pregnant or lactating women may not participate due to the embryotoxic effects of protocol treatment. Women/ men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
- Unable to have a contrast-enhanced MRI scan - standard of care criteria
- Patients on anthracycline or taxane based chemotherapy
- Patients with metallic or breast implants
- Subjects with inflammatory breast cancer, connective tissue disorder, musculoskeletal deformity
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Definity Suspension for InjectionMRI-guided ultrasound-stimulated microbubble-treatment | Drug | MRg-FUS MB Treatment |
Primary outcome
Incidence of toxicity and adverse events using MRg-FUS+MB treatment in patients with chest-wall and locally advanced breast cancer
Time frame: 90 days
Incidence of toxicity and adverse events
1 secondary outcome
Radiological Response
Time frame: 90 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2023.
- Derived from this study: PubMed 38758967Moore-Palhares D, Dasgupta A, Saifuddin M, Anzola Pena ML, Prasla S, Ho L, Lu L, Kung J, McNabb E, Sannachi L, Vesprini D, Chen H, Karam I, Soliman H, Szumacher E, Chow E, Gandhi S, Trudeau M, Curpen B, Stanisz GJ, Kolios M, Czarnota GJ. Radiation enhancement using focussed ultrasound-stimulated microbubbles for breast cancer: A Phase 1 clinical trial. PLoS Med. 2024 May 17;21(5):e1004408. doi: 10.1371/journal.pmed.1004408. eCollection 2024 May.
- Derived from this study: PubMed 37604988Dasgupta A, Saifuddin M, McNabb E, Ho L, Lu L, Vesprini D, Karam I, Soliman H, Chow E, Gandhi S, Trudeau M, Tran W, Curpen B, Stanisz G, Sahgal A, Kolios M, Czarnota GJ. Novel MRI-guided focussed ultrasound stimulated microbubble radiation enhancement treatment for breast cancer. Sci Rep. 2023 Aug 21;13(1):13566. doi: 10.1038/s41598-023-40551-5.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dr. Gregory Czarnota, MD principal investigator
Sunnybrook Health Sciences Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Definity Suspension for Injection in people with Breast Cancer, run by Sunnybrook Health Sciences Centre at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of toxicity and adverse events using MRg-FUS+MB treatment in patients with chest-wall and locally advanced breast cancer (time frame: 90 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04431674, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Dec 2023.