Metastatic Breast CancerPhase 1i-GONCT03749850
Image-guided Targeted Doxorubicin Delivery With Hyperthermia to Optimize Loco-regional Control in Breast Cancer
A Phase 1 study testing LTLD, MR-HIFU induced hyperthermia and Cyclophosphamide in people with Metastatic Breast Cancer and Breast Cancer, run by UMC Utrecht at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Metastatic Breast Cancer, Breast Cancer, Breast Neoplasms
- What is being tested?
- LTLD, MR-HIFU induced hyperthermia and Cyclophosphamide
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteNetherlands
- Study dates
- Mar 2021to Nov 2022
- 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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must meet all of the following inclusion criteria:
- Histologically confirmed adenocarcinoma of the breast and planned for palliative chemotherapy with doxorubicine en cyclophosphamide
- Biopsy-proven stage tumor 1-2, any nodes, metastasis 1 (T1-2AnyNM1) at diagnosis of breast cancer.
- Non-pregnant, non-lactating female at least 18 years of age. If patient is of 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.
- The tumor is located within the reach of the HIFU beam (based on pre-treatment Dynamic Contrast Enhanced (DCE-) MRI findings).
- The distance of the tumor from the skin, nipple, and pectoral wall is at least 1.0 cm (based on pre-treatment DCE-MRI findings).
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- The target breast is expected to fit in the cup of the dedicated MR-HIFU breast system (based on pre-treatment MRI findings).
- The patient weighs less than 90 kg (restrictment of the HIFU table top).
- Provide written informed consent and willing to comply with protocol requirements.
Who cannot join
- Patients will be excluded if any of the following conditions are observed:
- Her2-positive disease or classic invasive lobular carcinoma (ILC).
- A treatment plan with curative intent is available.
- Any prior chemotherapy treatment for invasive breast cancer (previous anti-hormonal therapy is allowed)
- Any prior therapy with anthracyclines
- No measurable disease at baseline (according to RECIST 1.1 or PERCIST 1.0)
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- Any concomitant malignancy or previous malignancy in the last 5 years, except basal cell or squamous cell cancer of the skin or in situ carcinoma of the cervix.
- Subjects with a prior contralateral breast malignancy more than 5 years ago can be included if they did not receive any chemotherapy.
- Any previous malignancy in the unilateral breast (even if more than 5 years ago)
- Prior sensitivity (including rash, dyspnea, wheezing, urticarial, or other symptoms) attributed to any liposomal-encapsulated drug.
- Baseline laboratory values:
- Absolute Neutrophil Count (ANC) < 1.5 x 10^9/L, Platelets < 75 x 10^9/L, Hemoglobin < 5.6 mmol/L (9 g/dl), Total Bilirubin > 1.5 x upper limit of normal, Alanine Transaminase (ALAT) and Aspartate Transaminase (ASAT) > 2.5 x upper limit of normal >5 x upper limit of normal in case of liver metastases, Estimated Glomerular Filtration Rate (eGFR) < 30 ml/min/1.73m2.
- World Health Organization Performance Status (WHO-PS) >2.
- Left Ventricular Ejection Fraction <50% (validated by baseline scan).
- History of:
- Acute coronary syndrome in the last year
- Cerebral vascular accident in the last year
- Abnormal cardiac stress testing within last 6 months
- Symptomatic coronary artery disease
- Uncontrolled hypertension or cardiomyopathy
- Cardiac valvular surgery or open heart surgery in the last year
- Known structural heart disease
- 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.
- Active infection
- Body temperature > 38.0 degrees Celsius on the day of a MR-HIFU treatment.
- 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 (Abelect, Ambisome, Nyotran, etc.) or lipid-complexed drugs.
- Caution will be exercised with all the medications mentioned in appendix C, for interactions are theoretically possible.
- Contraindications to MR imaging (e.g., pacemaker in situ, severe claustrophobia, metal implants incompatible with the MRI-scan, body size incompatible with MR bore).
- Contraindications to gadolinium-based contrast agent, including prior allergic reaction to gadolinium-based contrast agent, and/or renal failure.
- 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(57)) of 4; dependence on artificial ventilation at home; sleep apnea or an American Society of Anesthesiologists (ASA) classification ≥4.
- Inability to lie in prone position.
- A medical or psychiatric condition or other circumstances which would significantly decrease the chances of understanding the informed consent process, obtaining reliable data, achieving study objectives, or completing the study treatment and/or examinations.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
University Medical Center Utrecht
Utrecht, 3584 CX
About this study
Official title: 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
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.
Read more
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.
Read the detailed description
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.
- Conditions
- Metastatic Breast Cancer, Breast Cancer, Breast Neoplasms, Stage IV Breast Cancer, Metastatic Cancer, Invasive Ductal Carcinoma of Female Breast
- Being tested
- LTLD, MR-HIFU induced hyperthermia, Cyclophosphamide
- Keywords
- High Intensity Focused Ultrasound, lyso-thermosensitive liposomal doxorubicin, ThermoDox, MR-HIFU, mild local hyperthermia, local drug delivery, image-guided therapy, nanomedicine, liposome, doxorubicin, adriamycin, cyclophosphamide, HIFU, LTLD, hyperthermia, de novo stage IV, metastatic breast cancer
- Medical subject headings
- Breast Neoplasms, Neoplasm Metastasis, Carcinoma, Ductal, Breast, Hyperthermia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LTLDDrug
Also called ThermoDox, Lyso-Thermosensitive Liposomal Doxorubicin
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.
MR-HIFU induced hyperthermiaProcedure or surgery
Also called MR-HIFU, Magnetic Resonance guided High Intensity Focused Ultrasound, MLHT, Mild local 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.
CyclophosphamideDrug
Also called Endoxan
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.
| Study group | Role | What they receive |
|---|---|---|
| Study treatment | Experimental | LTLD in combination with MR-HIFU induced hyperthermia and cyclophosphamide
Single arm study Receives: Drug: LTLD; Procedure: MR-HIFU induced hyperthermia; Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events assessed by CTCAE v 5.0
Safety and tolerability of the study treatment
Measured: From first study treatment (day 1) until the end of study visit between day 161 and 175
Incidence of dose limiting toxicities
Safety and tolerability of the study treatment
Measured: From first study treatment (day 1) until the end of study visit between day 161 and 175
Incidence of necessity for dose adjustments, delay or early cessation
Safety and tolerability of the study treatment
Measured: From first study treatment (day 1) until the end of study visit between day 161 and 175
Incidence and severity of post-procedural pain
Safety and tolerability of the study treatment
Measured: From first study treatment (day 1) until the end of study visit between day 161 and 175
Patient reported tolerability via an adapted version of the Cancer Therapy Satisfaction Questionnaire (CTSQ)
Tolerability of the study treatment. Scores will be described.
Measured: Baseline, day 49 and day 112
Patient reported tolerability via the Functional Assessment of Cancer Therapy - Breast (FACT-B) questionnaire
Tolerability of the study treatment. Scores will be described.
Measured: Baseline, and on day 14 of each cycle (with a maximum of six 21-day cycles in 18 weeks)
Incidence of cardiotoxity
Safety and tolerability of the study treatment
Measured: From first study treatment (day 1) until the end of study visit between day 161 and 175
Description of MR thermometry data (describing the temperatures achieved)
Feasibility of the study treatment
Measured: On day 1 (study treatment day) of each cycle (with a maximum of six 21-day cycles in 18 weeks)
Duration of procedures on a treatment day
Feasibility of the study treatment
Measured: On day 1 (study treatment day) of each cycle (with a maximum of six 21-day cycles in 18 weeks)
Number of completed cycles with MR-HIFU induced hyperthermia, ThermoDox and cyclophosphamide
Feasibility of the study treatment
Measured: From first study treatment (day 1) until the end of study visit between day 161 and 175
The number of cycles in which hyperthermia was sufficient: at least 30 minutes at the target temperature of 40-42°C
Feasibility of the study treatment
Measured: From first study treatment (day 1) until the end of study visit between day 161 and 175
Secondary outcomes (2)
Radiological objective response locally on breast Magnetic Resonance Imaging, assessed by RECIST 1.1.
Efficacy of the study treatment
Measured: Assessed after 2 cycles and after 6 cycles of the study treatment. Each cycle is 21 days.
Radiological objective response systemically on Computed Tomography, assessed by RECIST 1.1 or (for patients without RECIST-measurable disease) Positron Emission Tomography Computed Tomography, assessed by PERCIST 1.0
Efficacy of the study treatment
Measured: Assessed after 2 cycles and after 6 cycles of the study treatment. Each cycle is 21 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2018
- Study startMar 2021 (estimated)
- Primary completionNov 2022 (estimated)
- Study completionNov 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- More trials run by UMC UtrechtThe 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
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- UMC Utrecht
- Sponsor type
- University, hospital or other
- Collaborators
- Dutch Cancer Society, Center for Translational Molecular Medicine, Vrienden UMC Utrecht
- Responsible party
- Principal investigator, BBM Suelmann, UMC Utrecht
- Investigators
- Britt BM Suelmann, MD, Principal investigator, UMC Utrecht
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03749850
- Sponsor's protocol ID
- NL67422.041.18
- Other IDs
- 2015-005582-23, 2015
- Acronym
- i-GO
- Status last verified
- Feb 2021
- First submitted
- 9 Nov 2018
- Last updated
- 17 Feb 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
de Maar JS, Suelmann BBM, Braat MNGJA, van Diest PJ, Vaessen HHB, Witkamp AJ, Linn SC, Moonen CTW, van der Wall E, Deckers R. Phase I feasibility study of Magnetic Resonance guided High Intensity Focused Ultrasound-induced hyperthermia, Lyso-Thermosensitive Liposomal Doxorubicin and cyclophosphamide in de novo stage IV breast cancer patients: study protocol of the i-GO study. BMJ Open. 2020 Nov 26;10(11):e040162. doi: 10.1136/bmjopen-2020-040162.
PubMed 33243800
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03749850
- Acronym / sponsor ID
- i-GO / NL67422.041.18
- Conditions
- Metastatic Breast Cancer, Breast Cancer, Breast Neoplasms, Stage IV Breast Cancer, Metastatic Cancer, Invasive Ductal Carcinoma of Female Breast
- Keywords
- High Intensity Focused Ultrasound, lyso-thermosensitive liposomal doxorubicin, ThermoDox, MR-HIFU, mild local hyperthermia, local drug delivery, image-guided therapy, nanomedicine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- UMC UtrechtUniversity, hospital or other
- Collaborators
- Dutch Cancer Society, Center for Translational Molecular Medicine, Vrienden UMC Utrecht
- Study start
- Mar 2021 (estimated)
- Primary completion
- Nov 2022 (estimated)
- Study completion
- Nov 2022 (estimated)
- First posted
- 21 Nov 2018 (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.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Study treatment | Experimental | Drug: LTLD, Procedure: MR-HIFU induced hyperthermia, Drug: CyclophosphamideLTLD in combination with MR-HIFU induced hyperthermia and cyclophosphamide Single arm study |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Histologically confirmed adenocarcinoma of the breast and planned for palliative chemotherapy with doxorubicine en cyclophosphamide
- Biopsy-proven stage tumor 1-2, any nodes, metastasis 1 (T1-2AnyNM1) at diagnosis of breast cancer.
- Non-pregnant, non-lactating female at least 18 years of age. If patient is of 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.
- The tumor is located within the reach of the HIFU beam (based on pre-treatment Dynamic Contrast Enhanced (DCE-) MRI findings).
- The distance of the tumor from the skin, nipple, and pectoral wall is at least 1.0 cm (based on pre-treatment DCE-MRI findings).
Key exclusion criteria (32 listed)
- Her2-positive disease or classic invasive lobular carcinoma (ILC).
- A treatment plan with curative intent is available.
- Any prior chemotherapy treatment for invasive breast cancer (previous anti-hormonal therapy is allowed)
- Any prior therapy with anthracyclines
- No measurable disease at baseline (according to RECIST 1.1 or PERCIST 1.0)
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 |
|---|---|---|
| LTLDAlso: ThermoDox, Lyso-Thermosensitive Liposomal DoxorubicinPatients 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. | Drug | Study treatment |
| MR-HIFU induced hyperthermiaAlso: MR-HIFU, Magnetic Resonance guided High Intensity Focused Ultrasound, MLHT, Mild local hyperthermiaPatients 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. | Procedure or surgery | Study treatment |
| CyclophosphamideAlso: EndoxanPatients 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. | Drug | Study treatment |
Primary outcome
Incidence of adverse events assessed by CTCAE v 5.0
Time frame: From first study treatment (day 1) until the end of study visit between day 161 and 175
Safety and tolerability of the study treatment
Incidence of dose limiting toxicities
Time frame: From first study treatment (day 1) until the end of study visit between day 161 and 175
Safety and tolerability of the study treatment
Incidence of necessity for dose adjustments, delay or early cessation
Time frame: From first study treatment (day 1) until the end of study visit between day 161 and 175
Safety and tolerability of the study treatment
Incidence and severity of post-procedural pain
Time frame: From first study treatment (day 1) until the end of study visit between day 161 and 175
Safety and tolerability of the study treatment
Patient reported tolerability via an adapted version of the Cancer Therapy Satisfaction Questionnaire (CTSQ)
Time frame: Baseline, day 49 and day 112
Tolerability of the study treatment. Scores will be described.
Patient reported tolerability via the Functional Assessment of Cancer Therapy - Breast (FACT-B) questionnaire
Time frame: Baseline, and on day 14 of each cycle (with a maximum of six 21-day cycles in 18 weeks)
Tolerability of the study treatment. Scores will be described.
Incidence of cardiotoxity
Time frame: From first study treatment (day 1) until the end of study visit between day 161 and 175
Safety and tolerability of the study treatment
Description of MR thermometry data (describing the temperatures achieved)
Time frame: On day 1 (study treatment day) of each cycle (with a maximum of six 21-day cycles in 18 weeks)
Feasibility of the study treatment
Duration of procedures on a treatment day
Time frame: On day 1 (study treatment day) of each cycle (with a maximum of six 21-day cycles in 18 weeks)
Feasibility of the study treatment
Number of completed cycles with MR-HIFU induced hyperthermia, ThermoDox and cyclophosphamide
Time frame: From first study treatment (day 1) until the end of study visit between day 161 and 175
Feasibility of the study treatment
The number of cycles in which hyperthermia was sufficient: at least 30 minutes at the target temperature of 40-42°C
Time frame: From first study treatment (day 1) until the end of study visit between day 161 and 175
Feasibility of the study treatment
2 secondary outcomes
Radiological objective response locally on breast Magnetic Resonance Imaging, assessed by RECIST 1.1.
Time frame: Assessed after 2 cycles and after 6 cycles of the study treatment. Each cycle is 21 days.
Radiological objective response systemically on Computed Tomography, assessed by RECIST 1.1 or (for patients without RECIST-measurable disease) Positron Emission Tomography Computed Tomography, assessed by PERCIST 1.0
Time frame: Assessed after 2 cycles and after 6 cycles of the study treatment. Each cycle is 21 days.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2021.
- Derived from this study: PubMed 33243800de Maar JS, Suelmann BBM, Braat MNGJA, van Diest PJ, Vaessen HHB, Witkamp AJ, Linn SC, Moonen CTW, van der Wall E, Deckers R. Phase I feasibility study of Magnetic Resonance guided High Intensity Focused Ultrasound-induced hyperthermia, Lyso-Thermosensitive Liposomal Doxorubicin and cyclophosphamide in de novo stage IV breast cancer patients: study protocol of the i-GO study. BMJ Open. 2020 Nov 26;10(11):e040162. doi: 10.1136/bmjopen-2020-040162.
- 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.
Britt BM Suelmann, MD principal investigator
UMC Utrecht
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 LTLD, MR-HIFU induced hyperthermia and Cyclophosphamide in people with Metastatic Breast Cancer and Breast Cancer, run by UMC Utrecht at 1 site in Netherlands.
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 9 inclusion and 32 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: status not confirmed, as of the sponsor's last update on 17 Feb 2021. 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 Netherlands. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Mirjam A de Visser, MD (+31(0)887563142, M.A.deVisser-30@umcutrecht.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of adverse events assessed by CTCAE v 5.0 (time frame: From first study treatment (day 1) until the end of study visit between day 161 and 175). The study lists 11 primary outcomes in all. 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 NCT03749850, which also lists 1 linked publication.
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 17 Feb 2021.