Pediatric CancerPhase 1NCT02536183
A Phase I Study of Lyso-thermosensitive Liposomal Doxorubicin and MR-HIFU for Pediatric Refractory Solid Tumors
A Phase 1 study testing Magnetic resonance high intensity focused ultrasound and Lyso-thermosensitive liposomal doxorubicin in people with Pediatric Cancer and Solid Tumors, run by AeRang Kim at 1 site in United States.
Trial summary
This study is looking to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of lyso-thermosensitive liposomal doxorubicin (LTLD) administered in combination with MR-HIFU in children with relapsed/refractory solid tumors, which may include but are not limited to rhabdomyosarcoma and other… Read more about this study
- Who is it for?
- Ages Up to 30 years
- Conditions the study is for
- Pediatric Cancer, Solid Tumors, Rhabdomyosarcoma
- What is being tested?
- Magnetic resonance 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
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2016to Oct 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 Up to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Part A: ≤21 years of age Part B: ≤ 30 years of age.
- DIAGNOSIS:
- Histologically confirmed malignant solid tumors, which may include but are not limited to rhabdomyosarcoma and other soft tissue sarcomas, Ewing's sarcoma family of tumors, osteosarcoma, neuroblastoma, Wilms' tumor, hepatic tumors, germ cell 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):
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- Radiographically evaluable or measurable 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.
- 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. 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 4 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 2 months post-autologous stem cell transplant or at least 3 months 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 peg-filgrastim, 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:
- Patients > 16 years old must have a Karnofsky performance level ≥ 50%, and children ≤ 16 years old must have a Lansky performance level ≥ 50%.
- 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:
- Age-adjusted normal serum creatinine OR a creatinine clearance ≥ 60 mL/min/1.73 m2.
- CARDIAC FUNCTION:
- Adequate Cardiac Function with Ejection Fraction > 50% by echocardiogram or cardiac MRI within 14 days prior to starting therapy.
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 methods 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 or scar tissue within the path of the HIFU beam.
- Target lesion <1 cm from nerve plexus, spinal canal, and bowel.
- Target lesion in contact with hollow viscera.
- Lesion in the skull.
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- Inability to undergo MRI and/or contraindication for MRI.
- 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 Medical Center
Washington D.C., District of Columbia, 20010
About this study
Official title: A Phase I Study of Lyso-thermosensitive Liposomal Doxorubicin (LTLD, ThermoDox®) and Magnetic Resonance-Guided High Intensity Focused Ultrasound (MR-HIFU) for Relapsed or Refractory Solid Tumors in Children, Adolescents, and Young Adults
This study is looking to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of lyso-thermosensitive liposomal doxorubicin (LTLD) administered in combination with MR-HIFU in children with relapsed/refractory solid tumors, which may include but are not limited to rhabdomyosarcoma and other soft tissue sarcomas, Ewing's sarcoma family of tumors, osteosarcoma, neuroblastoma, Wilms' tumor, hepatic tumors, and germ cell tumors.
Read the detailed description
This is phase 1 trial of LTLD with MR-HIFU induced heating in children and young adults with relapsed/refractory solid tumors.
Part A of the trial will be a traditional dose escalation study to determine the pediatric MTD/RP2D of LTLD combined with MR-HIFU ablation which allows for release of doxorubicin in the ablation zone and peri-ablation margins.
Part B of the trial will combine LTLD at the MTD/RP2D with MR-HIFU induced mild hyperthermia (MHT) in an expanded cohort.
- Conditions
- Pediatric Cancer, Solid Tumors, Rhabdomyosarcoma, Ewing Sarcoma, Soft Tissue Sarcomas, Osteosarcoma
- Being tested
- Magnetic resonance high intensity focused ultrasound, Lyso-thermosensitive liposomal doxorubicin
- Keywords
- Solid tumors, relapsed pediatric solid tumors, high intensity focused ultrasound, Lyso-thermosensitive liposomal doxorubicin, ThermoDox, relapsed sarcoma, Ewing Sarcoma family of tumors, Osteosarcoma, Neuroblastoma, Wilms Tumor, Hepatic Tumor, Germ Cell Tumors
- Medical subject headings
- Neoplasms, Rhabdomyosarcoma, Sarcoma, Ewing, Sarcoma, Osteosarcoma, Neuroblastoma, Wilms Tumor, Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Magnetic resonance high intensity focused ultrasoundDevice
Also called MR-HIFU
Magnetic resonance (MR)-high intensity focused ultrasound (HIFU) provides precise controlled delivery of heat by focusing ultrasound energy inside a lesion using an external applicator that is completely non-invasive and non-ionizing.
Lyso-thermosensitive liposomal doxorubicinDrug
Also called LTLD; ThermoDox
A heat-activated formulation of liposomal doxorubicin with unique property of heat-activated release of doxorubicin, an active agent in most pediatric solid tumors.
| Study group | Role | What they receive |
|---|---|---|
| Part A | Experimental | LTLD will be administered intravenously in combination with MR-HIFU ablation on day 1 of every 21 day cycle. There will be two potential dose escalation of LTLD with highest dose not to exceed the adult recommended MTD. Patients may receive up to a total of 6 cycles. Receives: Device: Magnetic resonance high intensity focused ultrasound; Drug: Lyso-thermosensitive liposomal doxorubicin |
| Part B | Experimental | LTLD at dose determined from Part A will be administered intravenously on day 1 of every 21 day cycle. MR-HIFU induced MHT will follow immediately post LTLD infusion for one hour to target area with target temperatures of 40-45°C. Patients may receive up to a total of 6 cycles Receives: Device: Magnetic resonance 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.
Maximum tolerated dose of LTLD
To determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of LTLD administered in combination with MR-HIFU ablation in children with relapsed/refractory solid tumors by examining blood samples collected from participants
Measured: 3 weeks
Toxicity profile of LTLD
To define and describe the toxicities of LTLD administered in combination with MR-HIFU as measured by reportable adverse events of participants as per the CTCAE v 4.0
Measured: up to 18 weeks
Pharmacokinetics of LTLD
Analyze blood samples of participants to characterize the pharmacokinetic properties of LTLD administered in combination with MR-HIFU
Measured: 8 days
Feasibility of treatment
To determine the feasibility of LTLD administered at the recommended dose in combination with MR-HIFU induced mild hyperthermia (MHT) as determined by patient outcomes and adverse events
Measured: up to 18 weeks
Secondary outcomes (3)
Antitumor Activity of the Treatment
To preliminarily determine the antitumor activity of LTLD with MR-HIFU within the confines of a phase 1 study by examining the response of target lesions using RECIST criteria v1.1
Measured: up to 18 weeks
Social Impact of the Treatment on Participants
To determine changes in symptoms and quality of life in children treated with LTLD and MR-HIFU by administering the Symptom Distress Scale and Peds QL v4.0 to participants
Measured: up to 18 weeks
Determine the Changes in Pharmacodynamic Immune Markers in Participants
To determine the changes in immune markers in children treated with LTLD and MR-HIFU by examining blood samples from participants
Measured: 3 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2015 (estimated)
- Study startOct 2016
- Primary completionOct 2022
- Study completionOct 2022
Why it stopped: low accrual
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 Pediatric CancerStudies of the same condition, open and under way.
- 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- AeRang Kim
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-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
- NCT02536183
- Sponsor's protocol ID
- HIFU Thermodox
- Status last verified
- Aug 2023
- First submitted
- 13 Aug 2015
- Last updated
- 29 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.
PubMed 31401903
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Lyso-thermosensitive Liposomal Doxorubicin (LTLD, ThermoDox®) and Magnetic Resonance-Guided High Intensity Focused Ultrasound (MR-HIFU) for Relapsed or Refractory Solid Tumors in Children, Adolescents, and Young Adults
- ClinicalTrials.gov ID
- NCT02536183
- Acronym / sponsor ID
- HIFU Thermodox
- Conditions
- Pediatric Cancer, Solid Tumors, Rhabdomyosarcoma, Ewing Sarcoma, Soft Tissue Sarcomas, Osteosarcoma
- Keywords
- Solid tumors, relapsed pediatric solid tumors, high intensity focused ultrasound, Lyso-thermosensitive liposomal doxorubicin, ThermoDox, relapsed sarcoma, Ewing Sarcoma family of tumors, Osteosarcoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: low accrual
- Enrolment
- 2 participants (actual)
- Lead sponsor
- AeRang KimUniversity, hospital or other
- Study start
- Oct 2016
- Primary completion
- Oct 2022 (actual)
- Study completion
- Oct 2022 (actual)
- First posted
- 31 Aug 2015 (estimated)
- 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 study is looking to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of lyso-thermosensitive liposomal doxorubicin (LTLD) administered in combination with MR-HIFU in children with relapsed/refractory solid tumors, which may include but are not limited to rhabdomyosarcoma and other soft tissue sarcomas, Ewing's sarcoma family of tumors, osteosarcoma, neuroblastoma, Wilms' tumor, hepatic tumors, and germ cell tumors.
Detailed description
This is phase 1 trial of LTLD with MR-HIFU induced heating in children and young adults with relapsed/refractory solid tumors.
Part A of the trial will be a traditional dose escalation study to determine the pediatric MTD/RP2D of LTLD combined with MR-HIFU ablation which allows for release of doxorubicin in the ablation zone and peri-ablation margins.
Part B of the trial will combine LTLD at the MTD/RP2D with MR-HIFU induced mild hyperthermia (MHT) in an expanded cohort.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part A | Experimental | Device: Magnetic resonance high intensity focused ultrasound, Drug: Lyso-thermosensitive liposomal doxorubicinLTLD will be administered intravenously in combination with MR-HIFU ablation on day 1 of every 21 day cycle. There will be two potential dose escalation of LTLD with highest dose not to exceed the adult recommended MTD. Patients may receive up to a total of 6 cycles. |
| Part B | Experimental | Device: Magnetic resonance high intensity focused ultrasound, Drug: Lyso-thermosensitive liposomal doxorubicinLTLD at dose determined from Part A will be administered intravenously on day 1 of every 21 day cycle. MR-HIFU induced MHT will follow immediately post LTLD infusion for one hour to target area with target temperatures of 40-45°C. Patients may receive up to a total of 6 cycles |
Who may qualify
- Ages
- Up to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (30 listed)
- Part A: ≤21 years of age Part B: ≤ 30 years of age.
- Histologically confirmed malignant solid tumors, which may include but are not limited to rhabdomyosarcoma and other soft tissue sarcomas, Ewing's sarcoma family of tumors, osteosarcoma, neuroblastoma, Wilms' tumor, hepatic tumors, germ cell tumors.
- 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.
- Radiographically evaluable or measurable solid tumor target lesion(s).
- 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.
Key exclusion criteria (11 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 methods 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 or scar tissue within the path of the HIFU beam.
- Target lesion <1 cm from nerve plexus, spinal canal, and bowel.
- Target lesion in contact with hollow viscera.
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 high intensity focused ultrasoundAlso: MR-HIFUMagnetic resonance (MR)-high intensity focused ultrasound (HIFU) provides precise controlled delivery of heat by focusing ultrasound energy inside a lesion using an external applicator that is completely non-invasive and non-ionizing. | Device | Part A, Part B |
| Lyso-thermosensitive liposomal doxorubicinAlso: LTLD; ThermoDoxA heat-activated formulation of liposomal doxorubicin with unique property of heat-activated release of doxorubicin, an active agent in most pediatric solid tumors. | Drug | Part A, Part B |
Primary outcome
Maximum tolerated dose of LTLD
Time frame: 3 weeks
To determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of LTLD administered in combination with MR-HIFU ablation in children with relapsed/refractory solid tumors by examining blood samples collected from participants
Toxicity profile of LTLD
Time frame: up to 18 weeks
To define and describe the toxicities of LTLD administered in combination with MR-HIFU as measured by reportable adverse events of participants as per the CTCAE v 4.0
Pharmacokinetics of LTLD
Time frame: 8 days
Analyze blood samples of participants to characterize the pharmacokinetic properties of LTLD administered in combination with MR-HIFU
Feasibility of treatment
Time frame: up to 18 weeks
To determine the feasibility of LTLD administered at the recommended dose in combination with MR-HIFU induced mild hyperthermia (MHT) as determined by patient outcomes and adverse events
3 secondary outcomes
Antitumor Activity of the Treatment
Time frame: up to 18 weeks
Social Impact of the Treatment on Participants
Time frame: up to 18 weeks
Determine the Changes in Pharmacodynamic Immune Markers in Participants
Time frame: 3 weeks
Results and safety
The study was stopped early (reason given: low accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2023.
- Derived from this study: PubMed 31401903Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.
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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 1 study testing Magnetic resonance high intensity focused ultrasound and Lyso-thermosensitive liposomal doxorubicin in people with Pediatric Cancer and Solid Tumors, run by AeRang Kim 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 30 inclusion and 11 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: stopped early, as of the sponsor's last update on 29 Aug 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 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 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 was stopped early (reason given: low accrual). Results are not available in the source record.
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?
Maximum tolerated dose of LTLD (time frame: 3 weeks). The study lists 4 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 NCT02536183, 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 29 Aug 2023.