Pasireotide as Maintenance Treatment with monthly deep intramuscular injection in SSTR2/3/5-Expressing Synovial Sarcoma and Desmoplastic Small Round Cell Tumor (PAMSARC)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 28
- 试验地点
- 3
- 主要终点
- Progression free survival (PFS), measured from study registration to radiologically confirmed disease progression according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1, or death from any cause, whichever occurs first (censoring of patients without an event at date of last follow-up)
研究概览
简要总结
To assess the clinical efficacy of pasireotide maintenance therapy for prolonging progression-free survival (PFS) in patients with SSTR2/3/5-expressing synovial sarcoma (SySa) and desmoplastic small round cell tumor (DSRCT)
详细描述
Desmoplastic small round cell tumor (DSRCT) is an extremely rare, aggressive sarcoma. It originates from the serosal surface of the abdominal cavity and the hallmark characteristic of DSRCT is the EWSR1-WT1 gene fusion. Synovial sarcoma (SySa) is also a rare fusion-gene driven (SS18-SSX1, SS18-SSX2, or rarely, SS18-SSX4) soft-tissue sarcoma.
Selected somatostatin receptor (SSTR) family members, i.e., SSTR2, SSTR3 and SSTR5, were highly expressed in patients with available transcriptome data, providing the basis for treatment with a somatostatin analog such as pasireotide with high affinity for SSTR1, 2, 3, and 5.
The primary aim of the study is to assess the clinical efficacy of pasireotide maintenance therapy for prolonging progression-free (PFS) and overall survival (OS) in patients with SSTR2/3/5-expressing advanced SySa and DSRCT. Furthermore measurable residual disease (MRD) before, during, and after pasireotide maintenance therapy are assessed. Pasireotide is applied in adults with 60 mg and in adolescents 60 mg (body surface area [BSA] >1.6 m²) or 40 mg (BSA 1.1-1.6 m²) via intragluteal via intragluteal depot injection every 28±3 days. The sample size is planned for the entire study population with subsequent sensitivity analysis in two subgroups, i.e., adolescents and adults. The primary efficacy analysis is be based on a two-sided, one-sample log-rank test using a significance level of 5%. The sample size was calculated assuming exponential data, planning for a power of 90% to detect a hazard ratio of 0.5. With a sample size of n=28, the expected number of events during the study is 22. Safety is assessed continuously according to CTCAE v5.0. The recruitment period is planned for 2 years starting in 2024 followed by a minimal follow-up of the last patient of 6 months leading to estimated trial completion in 2027.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 0 years 至 64 years（18-64 Years, 0-17 Years）
- 接受健康志愿者
- 是
入选标准
- •Reference pathological proven diagnosis of DSRCT in any stage; or Reference pathological proven diagnosis of SySa, IRS III, metastatic or relapsed disease
- •Female patients of childbearing potential and male patients with partners of childbearing potential who are sexually active must agree to the use of two forms of contraception in combination (male condom and one highly effective method). These should be started immediately after signing the informed consent form and continued throughout the period of study treatment plus 3 months for female and male patients. Male patients should refrain from fathering a child or donating sperm during the trial and for at least 3 months following the last dose.
- •Adequate bone marrow, renal, and hepatic function defined by laboratory tests within 14 days prior to study treatment (for details refer to protocol)
- •High SSTR2/3/5 mRNA expression, as determined by RNA sequencing within DKFZ/NCT/DKTK MASTER program
- •Stable disease, partial or complete response after completion of standard treatment
- •Age from 13 to 50 years
- •Bodyweight ≥ 30 kg
- •Lansky-Index ≥ 80% in patients < 16 years of age and Karnofsky-Index ≥ 80% in patients ≥ 16 years of age (including adults).
- •No curative treatment option
- •Time from last chemotherapy (at least 2 chemotherapy cycles) to enrollment <8 weeks
- •For women of childbearing potential negative urine pregnancy test at screening as well as highly effective forms of contraception have to be in place thereafter
排除标准
- •History of hypersensitivity to the investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product
- •Pregnancy/lactation
- •Prior treatment with somatostatin analog
- •Concurrent or previous treatment within 30 days in another interventional clinical trial / Participation in other ongoing clinical trials
- •Uncontrolled concurrent disease, in particular diabetes mellitus
- •Bleeding disorder
- •Therapeutic anticoagulation which cannot be paused temporarily in order to ensure safe intramuscular injection
- •Is taking or requiring any of the prohibited medication listed in 6.4.2
- •Heart rate at rest < 60/min
- •fasting glucose level > 110mg/dl
- •Severe neurologic or psychiatric disorder
结局指标
主要结局
Progression free survival (PFS), measured from study registration to radiologically confirmed disease progression according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1, or death from any cause, whichever occurs first (censoring of patients without an event at date of last follow-up)
Progression free survival (PFS), measured from study registration to radiologically confirmed disease progression according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1, or death from any cause, whichever occurs first (censoring of patients without an event at date of last follow-up)
次要结局
- Overall survival (OS), measured from study registration to death from any cause (censoring of patients without an event at date of last follow-up)
研究者
Coordinating Investigator
Scientific
Universitaetsklinikum Heidelberg AöR