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

ConditionsDesmoplastic Small Round Cell TumorOsteosarcomaRecurrent Desmoplastic Small Round Cell TumorRecurrent Kidney Wilms TumorRecurrent OsteosarcomaRefractory Desmoplastic Small Round Cell TumorRefractory Wilms TumorWilms Tumor
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age12-39
SponsorNational Cancer Institute (NCI)

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Oral

Intravaginal

Transdermal

Trial design

Design model

Single group

Treatments tested in this trial

  • Biospecimen Collection

    Procedure/Surgery

    Undergo blood sample collection

  • Computed Tomography

    Procedure/Surgery

    Undergo CT

  • Echocardiography Test

    Procedure/Surgery

    Undergo echocardiography

  • Magnetic Resonance Imaging

    Procedure/Surgery

    Undergo MRI

  • Multigated Acquisition Scan

    Procedure/Surgery

    Undergo MUGA

  • Trastuzumab Deruxtecan

    Biological/Vaccine

    Given IV

Treatment groups

55 Participants
are divided into 1 treatment group
Group A: Treatment (trastuzumab deruxtecan)Experimental treatment 6 interventions

Trial outcomes

Primary outcomes

1

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.

Time frame
During the first cycle of therapy (cycle length = 21 days)
2

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.

Time frame
Up to 30 days after last dose of study treatment
3

Time to progression

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

Time frame
Up to 1 year

Secondary outcomes

1

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

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.

Time frame
Up to 6 months
2

Response rates

Will be estimated by the uniform minimum variance unbiased estimator (Jung \& Kim, 2004) with one-sided 97% CI (Koyama and Chen, 2008).

Time frame
Up to 1 year
3

Duration of response

The duration of overall response is measured from the time measurement criteria are met for complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).

Time frame
Up to 1 year

Other outcomes

1

Progression-free survival (Phase 2)

Frequency (%) of evaluable patients who are event-free after 24 weeks (4-months) of therapy.

Time frame
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
2

Overall survival of DS-8201A

Median (95% CI) time-to-death estimated by Kaplan-Meier curves by dose level.

Time frame
Up to 1 year
3

Disease control rate

Will be estimated by the proportion of response-evaluable patients with complete response (CR), partial response (PR), or 24-weeks stable disease with exact, 95% confidence interval. Will be estimated overall and stratified by disease group.

Time frame
Up to 1 year
4

Objective response rate

Will be estimated separately for each Part B cohort. Will be estimated by the proportion with response (CR+PR) with a 95% exact Binomial confidence interval. Estimates will also be stratified by disease cohort.

Time frame
Up to 1 year

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

National Cancer Institute (NCI)

Lead sponsor

Source ClinicalTrials.gov
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