Trastuzumab Deruxtecan (DS-8201a) for the Treatment of Recurrent or Refractory Osteosarcoma, Wilms Tumor, and Desmoplastic Small Round Cell Tumor

NCT04616560 | Recruiting Phase 1 FDA Drug

• 3 other identifiers: NCI-2020-08428UM1CA228823PEPN1924
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 29

Brief Summary

This phase I/II trial studies the effects of trastuzumab deruxtecan (DS-8201a) in treating patients with osteosarcoma, Wilms tumor (WT) or desmoplastic small round cell tumor (DSRCT) that is newly diagnosed or has come back after a period of improvement (recurrent) or that has not responded to previous treatment (refractory). Trastuzumab deruxtecan is in a class of medications called antibody-drug conjugates. It is composed of a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called deruxtecan. Trastuzumab attaches to HER2 positive tumor cells in a targeted way and delivers deruxtecan to kill them.

Conditions

Osteosarcoma; Desmoplastic Small Round Cell Tumor; Recurrent Kidney Wilms Tumor; Recurrent Desmoplastic Small Round Cell Tumor; Recurrent Osteosarcoma; Refractory Desmoplastic Small Round Cell Tumor; Refractory Wilms Tumor; Wilms Tumor

Outcome Measures

Primary Outcomes (3)

• Maximum tolerated dose and/or recommended phase 2 dose of DS-8201a in children at least 2 to less than 12 years old with recurrent or refractory Wilms tumor (WT) or desmoplastic small round cell tumor (DSRCT) (Phase 1)

  The recommended dose will be determined by evaluation of safety, tolerability, and available pharmacokinetic and response data.

  During the first cycle of therapy (cycle length = 21 days)

• Incidence of adverse events (AEs) in children at least 2 to less than 12 years old with recurrent or refractory WT or DSRCT (Phase 1)

  Toxicity tables will be constructed to summarize the observed incidence by type of toxicity and grade. A patient will be counted only once for a given toxicity for the highest grade of that toxicity reported for that patient. Toxicity information recorded will include the type, severity, time of onset, time of resolution, and the probable association with the study regimen.

  Up to 30 days after last dose of study treatment

• Time to progression

  Median (95% confidence interval \[CI\]) time-to-progression estimated by Kaplan-Meier curves by dose level.

  Up to 1 year

Secondary Outcomes (3)

• Incidence of AEs of DS-8201A in children at least 12 years old with recurrent or refractory WT or DSRCT

  Up to 6 months

• Response rates

  Up to 1 year

• Duration of response

  Up to 1 year

Other Outcomes (4)

• Progression-free survival (Phase 2)

  From study enrollment until the first occurrence of an event, defined as relapse, disease progression or death from any cause, assessed up to 1 year

• Overall survival of DS-8201A

  Up to 1 year

• Disease control rate

  Up to 1 year

Study Arms (1)

Treatment (trastuzumab deruxtecan)

EXPERIMENTAL

Patients receive trastuzumab deruxtecan IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 35 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and MRI, echocardiography or MUGA, blood sample collection throughout the study.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Echocardiography Test; Procedure: Magnetic Resonance Imaging; Procedure: Multigated Acquisition Scan; Biological: Trastuzumab Deruxtecan

Interventions

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Treatment (trastuzumab deruxtecan)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (trastuzumab deruxtecan)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Treatment (trastuzumab deruxtecan)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA

Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide Ventriculography, RNV Scan, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning

Treatment (trastuzumab deruxtecan)

Trastuzumab Deruxtecan BIOLOGICAL

Given IV

Also known as: DS-8201, DS-8201a, Enhertu, Fam-trastuzumab Deruxtecan-nxki, T-DXd, WHO 10516

Treatment (trastuzumab deruxtecan)

Echocardiography Test PROCEDURE

Undergo echocardiography

Also known as: EC, Echocardiography

Treatment (trastuzumab deruxtecan)

Eligibility Criteria

• Age: 12 Years - 39 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Phase 1 (Part A): Patients must be at least 2 years and less than 12 years of age at the time of study enrollment
• Phase 2: Wilms tumor patients (Part B1): All Wilms tumor patients enrolled must be less than 18 years of age at enrollment
• Until the completion of the Phase 1 dose confirmation, patients must be at least 12 years of age and less than 18 years of age at the time of study enrollment
• Following dose confirmation of DS-8201a in children at least 2 to less than 12 years old in the Phase 1 component, Wilms tumor patients at least 2 to less than 18 years of age will be allowed on the Phase 2 component
• Phase 2: DSRCT patients (Part B2): Until the completion of the Phase 1 component, patients enrolling on the Phase 2 component of the study must be from at least 12 to 39 years of age at the time of study enrollment
• Following dose confirmation of DS-8201a in children at least 2 to less than 12 years old in the Phase 1 component, DSRCT patients at least 2 to 39 years of age will be allowed on the Phase 2 component
• Patients must have had histologic verification of Wilms tumor or desmoplastic small round cell tumor at original diagnosis or relapse
• Solid tumors: Patients must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Patients with clinically inactive brain metastases may be included in the study. Patients with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. Lastly, patient must have unresectable lesions or lesions with no intention to surgically remove the lesions in the 6 months following enrollment
• Wilms tumor: WT patients must have either refractory disease or a very high risk relapse, defined as ANY of the following:
• Relapse after initial treatment with 4 or more chemotherapy agents (e.g. Regimens vincristine, dactinomycin, doxorubicin, cyclophosphamide, etoposide and radiation \[M\], vincristine, dactinomycin and doxorubicin, vincristine, and irinotecan \[MVI\], doxorubicin, vincristine, cyclophosphamide, carboplatin, etoposide and radiation \[UH-1\], doxorubicin, vincristine, cyclophosphamide, carboplatin, etoposide, vincristine, and irinotecan \[UH-2\], vincristine, irinotecan, cyclophosphamide, carboplatin, etoposide and doxorubicin \[UH-3\], and etoposide, carboplatin, cyclophosphamide, and doxorubicin \[HR-1\])
• Relapse with high risk histology (anaplasia, blastemal predominant)
• Multiple relapses
• Desmoplastic small round cell tumor: DSRCT patients with relapsed or refractory disease are eligible
• Patient's current disease state must be one for which they have received at least standard initial therapy, defined as systemic therapy combined with either radiation or surgery for local control of the primary tumor at diagnosis. Prior therapy after relapse is not required
• Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0 or 1. Use Karnofsky for patients older than 16 years of age and Lansky for patients 16 years of age and younger

You may not qualify if:

• Pregnant, planning to become pregnant, or breast-feeding women will not be entered on this study. 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 two effective methods of birth control, including a medically accepted barrier or contraceptive method (e.g., male or female condom) for the duration of the study and upon completion of the study and for at least 7 months for females and 4 months for males after the last dose of study drug. Abstinence is an acceptable method of birth control
• Methods considered as highly effective methods of contraception include:
• Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
• Oral
• Intravaginal
• Transdermal
• Progestogen-only hormonal contraception associated with inhibition of ovulation:
• Oral
• Injectable
• Implantable
• Intrauterine device (IUD)
• Intrauterine hormone-releasing system (IUS)
• Bilateral tubal occlusion
• Vasectomized partner
• Complete sexual abstinence defined as refraining from heterosexual intercourse. Periodic abstinence (calendar, symptothermal, post-ovulation methods) is not an acceptable method of contraception

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (29)

Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

SUSPENDED

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

RECRUITING

Children's Hospital of Orange County

Orange, California, 92868, United States

SUSPENDED

Lucile Packard Children's Hospital Stanford University

Palo Alto, California, 94304, United States

SUSPENDED

UCSF Medical Center-Mission Bay

San Francisco, California, 94158, United States

SUSPENDED

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

SUSPENDED

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

SUSPENDED

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, 33701, United States

SUSPENDED

Children's Healthcare of Atlanta - Arthur M Blank Hospital

Atlanta, Georgia, 30329, United States

RECRUITING

Lurie Children's Hospital-Chicago

Chicago, Illinois, 60611, United States

SUSPENDED

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

RECRUITING

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

SUSPENDED

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

SUSPENDED

C S Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

SUSPENDED

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

SUSPENDED

Children's Mercy Hospitals and Clinics

Kansas City, Missouri, 64108, United States

SUSPENDED

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

SUSPENDED

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Duke University Medical Center

Durham, North Carolina, 27710, United States

RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

SUSPENDED

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

SUSPENDED

Saint Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

RECRUITING

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

ACTIVE NOT RECRUITING

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, 75390, United States

SUSPENDED

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, 77030, United States

ACTIVE NOT RECRUITING

Primary Children's Hospital

Salt Lake City, Utah, 84113, United States

SUSPENDED

Related Publications (1)

• Reed DR, Janeway KA, Minard CG, Hall D, Crompton BD, Lazar AJ, Wang WL, Zylber R, Contreras A, Carrero G, Voss SD, Reid JM, Safgren SL, Militano O, Gorlick R, Pickett CA, Fox E, Weigel BJ. PEPN1924, A Phase II Study of Trastuzumab Deruxtecan in Patients With Recurrent Human Epidermal Growth Factor Receptor 2+ Osteosarcoma: A Children's Oncology Group Pediatric Early-Phase Clinical Trial Network Study. JCO Oncol Adv. 2025;2:e2500094. doi: 10.1200/oa-25-00094. Epub 2025 Oct 14.

  PMID: 42131734 DERIVED

MeSH Terms

Conditions

Desmoplastic Small Round Cell Tumor; Osteosarcoma; Wilms Tumor

Interventions

Specimen Handling; Magnetic Resonance Spectroscopy; trastuzumab deruxtecan

Condition Hierarchy (Ancestors)

Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Complex and Mixed; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplastic Syndromes, Hereditary; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Damon R Reed

  Pediatric Early Phase Clinical Trial Network

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2020
• First Posted: November 5, 2020
• Study Start: March 8, 2021
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: August 6, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share

Locations

US (29)