Brief Title
A Phase I Study of Lyso-thermosensitive Liposomal Doxorubicin and MR-HIFU for Pediatric Refractory Solid Tumors
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
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.
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 Phase
Phase 1
Study Type
Interventional
Primary Outcome
Maximum tolerated dose of LTLD
Secondary Outcome
Antitumor Activity of the Treatment
Condition
Pediatric Cancer
Intervention
Magnetic resonance high intensity focused ultrasound
Study Arms / Comparison Groups
Part A
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Device
Estimated Enrollment
34
Start Date
October 2016
Completion Date
October 2021
Primary Completion Date
October 2021
Eligibility Criteria
Inclusion Criteria:
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.
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.
Exclusion Criteria:
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.
Gender
All
Ages
N/A - 30 Years
Accepts Healthy Volunteers
No
Contacts
AeRang Kim, MD, PhD, 202-476-6755, [email protected]
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT02536183
Organization ID
HIFU Thermodox
Responsible Party
Sponsor-Investigator
Study Sponsor
AeRang Kim
Study Sponsor
AeRang Kim, MD, PhD, Principal Investigator, Children's National Research Institute
Verification Date
February 2021