A Phase I Study of Lyso-thermosensitive Liposomal Doxorubicin and MR-HIFU for Pediatric Refractory Solid Tumors
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.
- Pediatric Cancer
- Solid Tumors
- Ewing Sarcoma
- Soft Tissue Sarcomas
- Wilms Tumor
- Hepatic Tumor
- Germ Cell Tumors
- Eligible Ages
- Under 30 Years
- Eligible Genders
- Accepts Healthy Volunteers
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.
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.
No other anti-cancer therapy (chemotherapy, biological therapy, radiation therapy) is permitted.
Patients > 16 years old must have a Karnofsky performance level ≥ 50%, and children ≤ 16 years old must have a Lansky performance level ≥ 50%.
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)).
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.
Age-adjusted normal serum creatinine OR a creatinine clearance ≥ 60 mL/min/1.73 m2.
Adequate Cardiac Function with Ejection Fraction > 50% by echocardiogram or cardiac MRI within 14 days prior to starting therapy.
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.
- Phase 1
- Study Type
- Intervention Model
- Single Group Assignment
- Primary Purpose
- None (Open Label)
|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.||
|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||
Children's National and nearby locations
- NCT ID
- AeRang Kim
Study ContactAnn Liew, MS, CCRP
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.