Study Stopped
low accrual
A Phase I Study of Lyso-thermosensitive Liposomal Doxorubicin and MR-HIFU for Pediatric Refractory Solid Tumors
1 other identifier
interventional
2
1 country
1
Brief 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 soft tissue sarcomas, Ewing's sarcoma family of tumors, osteosarcoma, neuroblastoma, Wilms' tumor, hepatic tumors, and germ cell tumors.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Oct 2016
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 13, 2015
CompletedFirst Posted
Study publicly available on registry
August 31, 2015
CompletedStudy Start
First participant enrolled
October 1, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
October 1, 2022
CompletedAugust 29, 2023
August 1, 2023
6 years
August 13, 2015
August 28, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
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
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
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
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
up to 18 weeks
Secondary Outcomes (3)
Antitumor Activity of the Treatment
up to 18 weeks
Social Impact of the Treatment on Participants
up to 18 weeks
Determine the Changes in Pharmacodynamic Immune Markers in Participants
3 weeks
Study Arms (2)
Part A
EXPERIMENTALLTLD 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
EXPERIMENTALLTLD 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
Interventions
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.
A heat-activated formulation of liposomal doxorubicin with unique property of heat-activated release of doxorubicin, an active agent in most pediatric solid tumors.
Eligibility Criteria
You may qualify if:
- 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):
- 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.
- +15 more criteria
You may not qualify if:
- 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.
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AeRang Kimlead
Study Sites (1)
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
Related Publications (1)
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.
PMID: 31401903DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
AeRang Kim, MD, PhD
Children's National Research Institute
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- MD, PhD
Study Record Dates
First Submitted
August 13, 2015
First Posted
August 31, 2015
Study Start
October 1, 2016
Primary Completion
October 1, 2022
Study Completion
October 1, 2022
Last Updated
August 29, 2023
Record last verified: 2023-08