A Phase 2 Study of DS-8201a (NSC# 807708) in Adolescents, or Young Adults With Recurrent HER2+ Osteosarcoma
概览
- 阶段
- 2 期
- 干预措施
- Biospecimen Collection
- 疾病 / 适应症
- Osteosarcoma
- 发起方
- National Cancer Institute (NCI)
- 入组人数
- 77
- 试验地点
- 53
- 主要终点
- Event-free survival of DS-8201A for HER2+ osteosarcoma
- 状态
- 暂停
- 最后更新
- 19天前
概览
简要总结
This phase II trial studies the effects of trastuzumab deruxtecan in treating patients with HER2 positive osteosarcoma that is newly diagnosed or has come back (recurrent). 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.
详细描述
PRIMARY OBJECTIVE: I. To estimate the proportion of patients with recurrent measurable osteosarcoma treated with trastuzumab deruxtecan (DS-8201a) who are event free (%EF) at 24 weeks. SECONDARY OBJECTIVES: I. To assess the safety of DS-8201a in patients with recurrent osteosarcoma. II. To describe the pharmacokinetics of DS-8201a in patients with recurrent osteosarcoma. III. To estimate the objective response rate (ORR), event free survival (EFS), overall survival (OS) and duration of response (DOR) of patients with recurrent, measurable osteosarcoma. EXPLORATORY OBJECTIVES: I. To describe the relationship between potential biomarkers and response to DS-8201a. II. To evaluate quantitative circulating tumor deoxyribonucleic acid (DNA) (ctDNA) and circulating tumor cells (CTCs) as a surrogate markers of response in recurrent osteosarcoma. OUTLINE: Patients receive trastuzumab deruxtecan intravenously (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 echocardiography or multigated acquisition scan (MUGA), blood sample collection throughout the study. After completion of study treatment, patients are followed up at 6 months.
研究者
入排标准
入选标准
- •Patients must be \> 12 years and =\< 39 years of age at the time of study enrollment
- •Patients must have had histologic verification of osteosarcoma at original diagnosis or relapse
- •Patients with diagnoses of osteosarcoma and confirmed HER2 expression of \> 10% of osteosarcoma cells are eligible for the intervention
- •Note: There is a mandatory tissue submission for HER2 staining during the Step 0 Eligibility Screening process. Metastatic tissue, when possible from the most recent relapse, is strongly preferred for HER2 staining over archival tissue from primary resection or diagnostic biopsy. The evaluation period for HER2 staining to determine eligibility for therapy will be less than 4 weeks from screening enrollment
- •Patients must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 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 in the 6 months following enrollment
- •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
- •Use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age. Patients who are non-ambulatory as a result of prior surgical treatment for osteosarcoma should be considered ambulatory for the purposes of assessing performance status
- •Patients must have recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately
排除标准
- •Pregnant, planning to become pregnant, or breast-feeding women will not be entered on this study because there is yet no available information regarding human fetal or teratogenic toxicities. 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:
- •Intravaginal
- •Transdermal
- •Progestogen-only hormonal contraception associated with inhibition of ovulation:
- •Injectable
- •Implantable
- •Intrauterine device (IUD)
- •Intrauterine hormone-releasing system (IUS)
研究组 & 干预措施
Treatment (trastuzumab deruxtecan)
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 echocardiography or MUGA, blood sample collection throughout the study.
干预措施: Biospecimen Collection
Treatment (trastuzumab deruxtecan)
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 echocardiography or MUGA, blood sample collection throughout the study.
干预措施: Echocardiography Test
Treatment (trastuzumab deruxtecan)
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 echocardiography or MUGA, blood sample collection throughout the study.
干预措施: Multigated Acquisition Scan
Treatment (trastuzumab deruxtecan)
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 echocardiography or MUGA, blood sample collection throughout the study.
干预措施: Trastuzumab Deruxtecan
结局指标
主要结局
Event-free survival of DS-8201A for HER2+ osteosarcoma
时间窗: At 24 weeks
Frequency (%) of evaluable patients who are event-free after 24 weeks (4-months) of therapy.
次要结局
- Overall survival of DS-8201A for HER2+ osteosarcoma(Up to 1 year)
- Event free survival of DS-8201A for HER2+ osteosarcoma(Up to 1 year)
- Incidence of adverse events of DS-8201A for HER2+ osteosarcoma(Up to 6 months)
- Time to progression of DS-8201A for HER2+ osteosarcoma(Up to 1 year)
- Duration of response(Up to 1 year)
- Response rates of DS-8201A for HER2+ osteosarcoma(Up to 1 year)