HIFU Hyperthermia With Liposomal Doxorubicin (DOXIL) for Relapsed or Refractory Pediatric and Young Adult Solid Tumors

NCT02557854 | Withdrawn Phase 1 DMC

• 1 other identifier: UTSW-HIFU-001
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether Doxil (liposomal doxorubicin) given prior to MR-HIFU Hyperthermia is safe for the treatment of pediatric and young adult patients with recurrent and refractory solid tumors.

Conditions

Rhabdomyosarcoma; Neuroblastoma; Sarcoma; Sarcoma, Ewing; Osteosarcoma; Desmoid

Outcome Measures

Primary Outcomes (1)

• Rate of dose limiting toxicities (DLTs) during cycle 1 of therapy with MR-HIFU hyperthermia directed liposomal doxorubicin

  Dose limiting toxicities are generally CTCAE v4.03 grade 3-5 toxicities with specific exceptions detailed in the protocol.

  4 weeks

Secondary Outcomes (7)

• Terminal half-life (T1/2) of Doxil when delivered with MR-HIFU hyperthermia

  48 hours following first dose

• Volume of distribution (L/m2) of Doxil when delivered with MR-HIFU hyperthermia

  48 hours following first dose

• Clearance (mL/min) of Doxil when delivered with MR-HIFU hyperthermia

  48 hours following first dose

• Adverse events associated with Doxil when administered in combination with MR-HIFU hyperthermia

  6 months

• Percentage of patients with relapsed or refractory solid tumors treated with MR-HIFU hyperthermia and Doxil who demonstrate disease progression at a MR-HIFU treated lesion

  Through study completion, an average of 1 year

Study Arms (1)

Doxil + MR-HIFU Hyperthermia

EXPERIMENTAL

Liposomal doxorubicin (Doxil) 50mg IV every 4 weeks followed by Magnetic Resonance High Intensity Focused Ultrasound hyperthermia (MR-HIFU) with Philips Sonalleve System to 42C for 30 minutes every 4 weeks

Drug: Doxorubicin HCl liposomal injection; Device: Philips Sonalleve MR-HIFU Hyperthermia

Interventions

Doxorubicin HCl liposomal injection DRUG

50mg IV every 4 weeks

Also known as: Doxil

Doxil + MR-HIFU Hyperthermia

Philips Sonalleve MR-HIFU Hyperthermia DEVICE

Hyperthermia to 42C for 30 minutes every 4 weeks

Doxil + MR-HIFU Hyperthermia

Eligibility Criteria

• Age: 1 Year - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age 1-40 years
• Histologically confirmed malignant extra-cranial solid tumor or demoid fibromatosis
• The subject's tumor must have relapsed after or failed to respond to frontline therapy and there must be no other known curative therapies available. Patients with desmoid fibromatosis must have relapsed after or failed to respond to at least one prior line of therapy, and in the opinion of the treating physician surgical resection of the tumor must not be possible without an amputation or other surgery predicted to result in an unacceptable functional deficit.
• Subject must have a life expectancy of \> 8 weeks
• Karnofsky performance status \> 50% for patients \>16 years of age, or Lansky performance status \> 50% for patients \< 16 years of age.
• The subject must have at least 1 measurable target lesion \>10mm in longest dimension that is in an anatomic location treatable by MR-HIFU. Note that for this study, lesions in bone WILL be considered measurable provided they meet the other criteria by RECIST and are confirmed to be metabolically active on baseline studies by either MIBG uptake (for neuroblastomas) or PET avidity. Target lesions should be located so that they can be adequately heated by a hyperthermia treatment cell with a diameter of up to 58 mm, centered at a depth of 35 to 80 mm from the skin. There should be no staples, implants, extensive scarring, or other highly ultrasound absorbing or reflecting tissue in the expected beam path. For the first 5 patients enrolled on this study only, the lesion must be located in the extremities or pelvis to be considered treatable by MR-HIFU.
• The subject must have recovered from the acute toxic effects of all prior therapy with the exception of alopecia. The following time must have elapsed from the last dose of the following medications to study enrollment:
• myelosuppressive chemotherapy 14 days
• hematopoetic growth factors 7 days (14 days for Neulasta)
• biologic agent 7 days
• monoclonal antibody 3 half-lives
• immunotherapy (ie tumor vaccines) 42 days
• palliative small port XRT 14 days
• substantial bone marrow XRT 6 weeks
• stem cell transplant or infusion without TBI 12 weeks

You may not qualify if:

• Subjects may not be receiving any other investigational agents or anticancer therapies.
• Subjects with known active brain metastases will be excluded from this clinical trial. Patients with brain metastases that have been treated and stable for \> 30 days following treatment will be eligible.
• Subjects who have received prior Doxil and progressed on this therapy are not eligible, but subjects may have received prior doxorubicin.
• Subjects with a history of tumor progression within 30 days of anthracycline administration are not eligible. However, subjects who have previously received an anthracycline and subsequently relapse greater than 30 days after their most recent prior dose of anthracycline will be eligible.
• History of allergic reactions attributed to doxorubicin or Doxil
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
• Subjects with a contraindication to MR-HIFU
• Subjects with conditions that carry high anesthetic risk in the opinion of the treating anesthesiologist are not eligible (i.e. subjects with significant airway compression by tumor or craniofacial abnormalities)

Sponsors & Collaborators

• Theodore Laetsch: lead

Study Sites (1)

UT Southwestern Medical Center/Children's Medical Center

Dallas, Texas, 75390, United States

Location

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: 31401903 DERIVED

MeSH Terms

Conditions

Rhabdomyosarcoma; Neuroblastoma; Sarcoma; Sarcoma, Ewing; Osteosarcoma; Desmoid Tumors

Interventions

liposomal doxorubicin

Condition Hierarchy (Ancestors)

Myosarcoma; Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Fibroma; Neoplasms, Fibrous Tissue

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Pediatrics

Study Record Dates

• First Submitted: September 21, 2015
• First Posted: September 23, 2015
• Study Start: December 1, 2016
• Primary Completion: March 16, 2019
• Study Completion: March 16, 2019
• Last Updated: March 19, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)