Solid TumorsPhase 2NCT04791228
A Pilot Study of Thermodox and MR-HIFU for Treatment of Relapsed Solid Tumors
A Phase 2 study testing Magnetic Resonance-Guided High Intensity Focused Ultrasound and Lyso-thermosensitive Liposomal Doxorubicin in people with Solid Tumors and Soft Tissue Sarcoma, run by Children's National Research Institute at 1 site in United States.
Trial summary
This is a pilot study of LTLD with MR-HIFU hyperthermia followed by ablation in subjects with refractory/relapsed solid tumors. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Solid Tumors, Soft Tissue Sarcoma, Ewing Sarcoma
- What is being tested?
- Magnetic Resonance-Guided High Intensity Focused Ultrasound and Lyso-thermosensitive Liposomal Doxorubicin
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Nov 2022to 23 Dec 2024
- Phase
- Phase 2
- 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 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- AGE: ≥ 12 years of age.
- DIAGNOSIS: Histologically confirmed malignant solid tumors
- TUMOR LOCATION: Patient must have at least one tumor located in areas accessible to HIFU, which will be defined as the target lesion(s). Target lesions must be reachable within the normal safety margins of HIFU as specified in the instructions for use.
- TARGET LESION(S): Radiographically measurable/evaluable solid tumor target lesion(s).
- THERAPEUTIC OPTIONS:
- Malignant Tumor: The patient's cancer must have relapsed after or failed to respond to frontline curative therapy and there must not be other potentially curative treatment options available.
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- PRIOR THERAPY:
- Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering on this study.
- No limitation on the number of prior chemotherapy regimens that the patient may have received prior to study entry.
- Myelosuppressive chemotherapy: The last dose of all myelosuppressive anticancer drugs must be at least 3 weeks prior to study entry (6 weeks for prior nitrosoureas) Prior treatment with anthracyclines is allowed as long as total cumulative dose is ≤ 450 mg/m2.
- Immunotherapy: The last dose of immunotherapy (monoclonal antibody or vaccine) must be at least 3 weeks prior to study entry.
- Biologic (anti-cancer agent): The last dose of all biologic agents for the treatment of the patient's cancer (such as retinoids or tyrosine kinase inhibitors) must be at least 7 days prior to study entry.
- Radiation therapy: The last dose of radiation to more than 25% of marrow containing bones (pelvis, spine, skull) must be at least 4 weeks prior to study entry. The last dose of all other local palliative (limited port) radiation must be at least 2 weeks prior to study entry.
- Stem Cell Transplantation. At least 42 days post-autologous stem cell transplant or at least 90 post-allogeneic transplant and recovered from toxicities without evidence of graft versus host disease and on stable doses of immunosuppressive medications if required.
- Growth Factors. The last dose of colony stimulating factors, such as filgrastim, sargramostim, and erythropoietin, must be at least 1 week prior to study entry, the last dose of long-acting colony stimulating factors, such as pegfilgrastim, must be at least 2 weeks prior to study entry.
- CONCURRENT THERAPIES:
- No other anti-cancer therapy (chemotherapy, biological therapy, radiation therapy) is permitted.
- PERFORMANCE STATUS:
- Lansky/Karnofsky performance level ≥ 50% (See Appendix I).
- Patients who are unable to walk because of paralysis or motor weakness, but who are up in a wheelchair will be considered ambulatory for the purpose of calculating the performance score.
- HEMATOLOGIC FUNCTION:
- Peripheral absolute neutrophil count (ANC) of ≥ 1000/µL.
- Platelet count ≥ 75,000/µL (transfusion independent (no transfusion within at least 7 days prior to enrollment)).
- HEPATIC FUNCTION:
- Total bilirubin must be ≤ 1.5 times the upper limit of normal (ULN) for age and gender.
- SGPT (ALT) must be ≤ 3.0 times the upper limit of normal for age.
- RENAL FUNCTION: Serum creatinine ≤ ULN for age/sex OR a creatinine clearance ≥60 mL/min/1.73 m2.
- CARDIAC FUNCTION: Adequate Cardiac Function with Ejection Fraction > 50% by echocardiogram.
Who cannot join
- Clinically significant unrelated systemic illness, such as serious infections, hepatic, renal or other organ dysfunction, which in the judgment of the Principal or Associate Investigator would compromise the patient's ability to tolerate study interventions.
- Patients who are pregnant or breast-feeding are not eligible for this study due to risks of fetal and teratogenic adverse events seen in animal/human studies with doxorubicin. Negative pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method beginning at the signing of informed consent and until at least 30 days after the last dose of study drug. The definition of adequate contraception will be based on the judgment of the principal investigator or designated associate.
- Implant or prosthesis within the path of the HIFU beam.
- Target pathway <1 cm from nerve plexus, spinal canal, or bowel.
- Target lesion in the skull.
- Inability to undergo MRI and/or contraindication for MRI.
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- Inability to tolerate stationary position during HIFU.
- Previous history of hypersensitivity to doxorubicin or its liposomal formulations.
- Patients currently receiving other anticancer agents.
- Patients currently receiving other investigational agents.
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's National Hospital
Washington D.C., District of Columbia, 20010
About this study
Official title: A Pilot Study of Lyso-thermosensitive Liposomal Doxorubicin (LTLD, ThermoDox®) and Magnetic Resonance-Guided High Intensity Focused Ultrasound (MR-HIFU) for Treatment of Relapsed or Refractory Solid Tumors
This is a pilot study of LTLD with MR-HIFU hyperthermia followed by ablation in subjects with refractory/relapsed solid tumors.
Read the detailed description
LTLD is a heat-activated formulation of liposomal doxorubicin that releases the drug when exposed to hyperthermic conditions (40-45°C). This novel agent has been well tolerated in adults with similar toxicity profile to doxorubicin. MR-HIFU offers a non-invasive and non-ionizing ability to selectively heat large tissue volumes. Thus, MR-HIFU is a promising technology for triggering doxorubicin release from LTLD. The investigator's approach involves continuous maintenance of the target at mild hyperthermia with MR-HIFU following LTLD infusion. Following hyperthermia, the investigators will deliver ablation therapy (>55°C) to targeted areas of tumor where feasible and safe. Addition of this ablation therapy after mild-hyperthermia-triggered drug delivery with LTLD has the potential to significantly potentiate chemotherapy with minimal additional adverse effects to improve local control and drug delivery without increasing toxicity.
- Conditions
- Solid Tumors, Soft Tissue Sarcoma, Ewing Sarcoma, Malignant Epithelial Neoplasm, Rhabdomyosarcoma, Wilms Tumor
- Being tested
- Magnetic Resonance-Guided High Intensity Focused Ultrasound, Lyso-thermosensitive Liposomal Doxorubicin
- Keywords
- Relapsed/refractory solid tumors, High Intensity Focused Ultrasound, Lyso-thermosensitive Liposomal Doxorubicin, ThermoDox
- Medical subject headings
- Sarcoma, Sarcoma, Ewing, Carcinoma, Rhabdomyosarcoma, Wilms Tumor, Carcinoma, Hepatocellular, Neoplasms, Germ Cell and Embryonal, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Magnetic Resonance-Guided High Intensity Focused UltrasoundDevice
Also called MR-HIFU
Magnetic resonance (MR)-guided high intensity focused ultrasound (HIFU) provides precise and controlled delivery of heat by focusing ultrasound energy inside a lesion using an external applicator without the need for a scalpel or needle.
Additional therapeutic advantages of this modality include its range of bioeffects, including both high temperature tumor ablation via coagulative necrosis, and effects of lower temperature, mild hyperthermia that can help to enhance local drug delivery to tumors. Both tumor ablation and hyperthermia may be employed to potentiate the effects of chemotherapy.
Lyso-thermosensitive Liposomal DoxorubicinDrug
Also called LTLD, ThermoDox
LTLD combines doxorubicin with lyso-thermosensitive liposomes that can selectively deliver drug to tumors and when exposed to temperatures greater than 40°C, rapidly and locally releases doxorubicin in high concentrations from systemically administered LTLD.
If combined with hyperthermia, doxorubicin will be released in the heated tumor margins and in any areas within the tumor that were not completely ablated and increase the likelihood of complete tumor necrosis. LTLD will extend tumor cell death to the hyperthermic regions in the peri-ablation zones and minimize the possibility of incomplete ablation or tumor recurrence.
| Study group | Role | What they receive |
|---|---|---|
| All Patients | Experimental | LTLD 50 mg/m2 will be administered intravenously over 30 minutes on day 1 of every 21-day cycle. MR-HIFU hyperthermia will follow infusion (+/- 30 minutes) for one hour to a target area with a target temperature of 40-45°C followed by ablation therapy (>55°C). The HIFU hyperthermia regimen will have a duration of at least 60 minutes and will then be followed by ablation therapy. Patients may receive up to a total of 6 cycles. Subsequent treatment cycles may treat alternative target lesions. Disease status will be evaluated using standard imaging techniques (CT/MR) post each cycle. Receives: Device: Magnetic Resonance-Guided High Intensity Focused Ultrasound; Drug: Lyso-thermosensitive Liposomal Doxorubicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary objective 1: Response of treated target lesion(s) assessed by CT or MRI
The Response Evaluation Criteria in Solid Tumors (RECIST v1.1) will be used
Measured: At the end of every 21-day cycle
Primary objective 2: The number of participants with treatment-related adverse events as assessed by the Common Terminology Criteria of Adverse Events (CTCAE) v.5
CTCAE v.5 will be used
Measured: Up to thirty days after last dose of protocol therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2021
- Study start10 Nov 2022
- Primary completion23 Dec 2024
- Study completion23 Dec 2024
Why it stopped: Low enrollment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumorsStudies of the same condition, open and under way.
- More trials run by Children's National Research InstituteThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's National Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, AeRang Kim, Children's National Research Institute
- Investigators
- AeRang Kim, MD, PhD, Principal investigator, Children's National Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04791228
- Sponsor's protocol ID
- HIFU Thermodox PII
- Status last verified
- Dec 2024
- First submitted
- 22 Feb 2021
- Last updated
- 1 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 1 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Lyso-thermosensitive Liposomal Doxorubicin (LTLD, ThermoDox®) and Magnetic Resonance-Guided High Intensity Focused Ultrasound (MR-HIFU) for Treatment of Relapsed or Refractory Solid Tumors
- ClinicalTrials.gov ID
- NCT04791228
- Acronym / sponsor ID
- HIFU Thermodox PII
- Conditions
- Solid Tumors, Soft Tissue Sarcoma, Ewing Sarcoma, Malignant Epithelial Neoplasm, Rhabdomyosarcoma, Wilms Tumor
- Keywords
- Relapsed/refractory solid tumors, High Intensity Focused Ultrasound, Lyso-thermosensitive Liposomal Doxorubicin, ThermoDox
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Low enrollment.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Children's National Research InstituteUniversity, hospital or other
- Study start
- 10 Nov 2022 (actual)
- Primary completion
- 23 Dec 2024 (actual)
- Study completion
- 23 Dec 2024 (actual)
- First posted
- 10 Mar 2021 (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.
This is a pilot study of LTLD with MR-HIFU hyperthermia followed by ablation in subjects with refractory/relapsed solid tumors.
Detailed description
LTLD is a heat-activated formulation of liposomal doxorubicin that releases the drug when exposed to hyperthermic conditions (40-45°C). This novel agent has been well tolerated in adults with similar toxicity profile to doxorubicin. MR-HIFU offers a non-invasive and non-ionizing ability to selectively heat large tissue volumes. Thus, MR-HIFU is a promising technology for triggering doxorubicin release from LTLD. The investigator's approach involves continuous maintenance of the target at mild hyperthermia with MR-HIFU following LTLD infusion. Following hyperthermia, the investigators will deliver ablation therapy (>55°C) to targeted areas of tumor where feasible and safe. Addition of this ablation therapy after mild-hyperthermia-triggered drug delivery with LTLD has the potential to significantly potentiate chemotherapy with minimal additional adverse effects to improve local control and drug delivery without increasing toxicity.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| All Patients | Experimental | Device: Magnetic Resonance-Guided High Intensity Focused Ultrasound, Drug: Lyso-thermosensitive Liposomal DoxorubicinLTLD 50 mg/m2 will be administered intravenously over 30 minutes on day 1 of every 21-day cycle. MR-HIFU hyperthermia will follow infusion (+/- 30 minutes) for one hour to a target area with a target temperature of 40-45°C followed by ablation therapy (>55°C). The HIFU hyperthermia regimen will have a duration of at least 60 minutes and will then be followed by ablation therapy. Patients may receive up to a total of 6 cycles. Subsequent treatment cycles may treat alternative target lesions. Disease status will be evaluated using standard imaging techniques (CT/MR) post each cycle. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (28 listed)
- AGE: ≥ 12 years of age.
- DIAGNOSIS: Histologically confirmed malignant solid tumors
- TUMOR LOCATION: Patient must have at least one tumor located in areas accessible to HIFU, which will be defined as the target lesion(s). Target lesions must be reachable within the normal safety margins of HIFU as specified in the instructions for use.
- TARGET LESION(S): Radiographically measurable/evaluable solid tumor target lesion(s).
- THERAPEUTIC OPTIONS:
Key exclusion criteria (10 listed)
- Clinically significant unrelated systemic illness, such as serious infections, hepatic, renal or other organ dysfunction, which in the judgment of the Principal or Associate Investigator would compromise the patient's ability to tolerate study interventions.
- Patients who are pregnant or breast-feeding are not eligible for this study due to risks of fetal and teratogenic adverse events seen in animal/human studies with doxorubicin. Negative pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method beginning at the signing of informed consent and until at least 30 days after the last dose of study drug. The definition of adequate contraception will be based on the judgment of the principal investigator or designated associate.
- Implant or prosthesis within the path of the HIFU beam.
- Target pathway <1 cm from nerve plexus, spinal canal, or bowel.
- Target lesion in the skull.
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 |
|---|---|---|
| Magnetic Resonance-Guided High Intensity Focused UltrasoundAlso: MR-HIFUMagnetic resonance (MR)-guided high intensity focused ultrasound (HIFU) provides precise and controlled delivery of heat by focusing ultrasound energy inside a lesion using an external applicator without the need for a scalpel or needle. Additional therapeutic advantages of this modality include its range of bioeffects, including both high temperature tumor ablation via coagulative necrosis, and effects of lower temperature, mild hyperthermia that can help to enhance local drug delivery to tumors. Both tumor ablation and hyperthermia may be employed to potentiate the effects of chemotherapy. | Device | All Patients |
| Lyso-thermosensitive Liposomal DoxorubicinAlso: LTLD, ThermoDoxLTLD combines doxorubicin with lyso-thermosensitive liposomes that can selectively deliver drug to tumors and when exposed to temperatures greater than 40°C, rapidly and locally releases doxorubicin in high concentrations from systemically administered LTLD. If combined with hyperthermia, doxorubicin will be released in the heated tumor margins and in any areas within the tumor that were not completely ablated and increase the likelihood of complete tumor necrosis. LTLD will extend tumor cell death to the hyperthermic regions in the peri-ablation zones and minimize the possibility of incomplete ablation or tumor recurrence. | Drug | All Patients |
Primary outcome
Primary objective 1: Response of treated target lesion(s) assessed by CT or MRI
Time frame: At the end of every 21-day cycle
The Response Evaluation Criteria in Solid Tumors (RECIST v1.1) will be used
Primary objective 2: The number of participants with treatment-related adverse events as assessed by the Common Terminology Criteria of Adverse Events (CTCAE) v.5
Time frame: Up to thirty days after last dose of protocol therapy
CTCAE v.5 will be used
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jan 2025.
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A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
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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.
AeRang Kim, MD, PhD principal investigator
Children's National Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Magnetic Resonance-Guided High Intensity Focused Ultrasound and Lyso-thermosensitive Liposomal Doxorubicin in people with Solid Tumors and Soft Tissue Sarcoma, run by Children's National Research Institute at 1 site in United States.
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 28 inclusion and 10 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: withdrawn, as of the sponsor's last update on 1 Jan 2025. 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 United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 was withdrawn before enrolling participants, so there are no results.
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?
Primary objective 1: Response of treated target lesion(s) assessed by CT or MRI (time frame: At the end of every 21-day cycle). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 Jan 2025.