A Multicenter, Open-label, Interventional Phase I Trial to Determine the Dose and Evaluate the Pharmacokinetics (PK) and Safety of Lutetium Lu 177 Edotreotide Targeted Radiopharmaceutical Therapy (RPT) as Monotherapy or Following Standard of Care (SoC) for the Treatment of Somatostatin Receptor-positive Tumors in the Pediatric Population (KinLET).
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 8
- 主要终点
- Pediatric Dosage
研究概览
简要总结
The purpose of the study is to determine the appropriate pediatric dosage and evaluate the pharmacokinetics (PK) and safety of Lutetium Lu 177 Edotreotide Targeted Radiopharmaceutical Therapy (RPT) as a monotherapy or following standard of care (SoC) in participants ≥2 to <18 years of age with somatostatin receptor (SSTR)-positive tumors.
详细描述
Determine the dose, pharmacokinetics and safety of Lutetium Lu 177 Edotreotide as monotherapy or following sequential standard of care in pediatric participants with recurrent, progressive or refractory NET, CNS, lymphoma and other solid tumors that express SSTRs by immunohistochemistry and demonstrate uptake by somatostatin receptor imaging. Lutetium Lu 177 Edotreotide will be given intravenously once every 8 weeks for a total of up to 6 doses over an average of 48 weeks in participants aged 2-18 years.
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
- 24 Months 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants aged ≥ 2 years and < 18 years
- •Confirmed diagnosis somatostatin receptor-positive (SSTR-positive) disease.
- •Tumor which is relapsed or is refractory to at least one line of previous therapy
- •Positive SSTR protein expression confirmed by immunohistochemistry of a tumor histology sample
- •Radioactivity uptake within the primary tumor or metastatic tumor sites measured by locally available SRIs ( 111In-based, 99mTc-based, or 68Ga-based SSTR single-photon emission computed tomography (SPECT)/ computed tomography (CT) or positron emission tomography (PET)/CT imaging, which is higher than the liver uptake)
- •Participants must have recovered from the acute treatment related toxicities (defined as ≤ grade 1 if not defined in eligibility criteria, excluding alopecia, stable treated electrolyte abnormalities on replacement and stable treated hypothyroidism) of all prior treatment modality prior to entering this trial
- •In case of sequential treatment followed by SoC or prior therapy, washout period applies before starting targeted RPT
- •Screening Consent Participant/legal guardian is willing to sign a screening consent. The screening consent is to be obtained according to institutional guidelines. Assent, when appropriate, will be obtained according to institutional guidelines.
排除标准
- •Known hypersensitivity to Lutetium Lu 177 Edotreotide, DOTA/Edotreotide, or excipients
- •Previous history of acute leukemia unless in remission for at least two years
- •Extensive bone/bone marrow involvement as per Investigator's judgement unless peripheral blood stem cells (PBSC) are available at a minimum of 2.5x106 CD34+ cells/kg
- •Patients who have received previous systemic targeted RPT
- •Previous treatment with metaiodobenzyl guanidine (MIBG) if the predicted overall exposure is expected to exceed 2 Gy (gray) to the bone marrow or 23 Gy to the kidney.
- •Previous treatment with external beam radiation therapy (EBRT) if the predicted overall exposure is expected to exceed more than 2 Gy to the bone marrow or 23 Gy to the kidney.
- •Previous treatment with oncologic immune vaccine or CAR-T cell therapy
- •Bulky disease in the CNS
- •Presence of severe renal, hepatic, electrolyte, cardiovascular, or hematological dysfunction
- •Participants who have received a live-attenuated vaccine up to four weeks prior to enrolment
- •Pregnant or breastfeeding women.
- •Other known malignancies.
- •Serious non-malignant disease.
研究组 & 干预措施
Three sequential age cohorts
Arms are based upon age at enrollment. The opening of the 2nd and 3rd cohort will depend on the recruitment of at least four participants with dosimetry and safety data for cycle 1, in the previous cohort.
- ≥ 12 to < 18 years old
- ≥ 6 years to < 12 years old
- ≥ 2 to < 6 years old
干预措施: Lutetium Lu 177-Edotreotide (Drug)
Three sequential age cohorts
Arms are based upon age at enrollment. The opening of the 2nd and 3rd cohort will depend on the recruitment of at least four participants with dosimetry and safety data for cycle 1, in the previous cohort.
- ≥ 12 to < 18 years old
- ≥ 6 years to < 12 years old
- ≥ 2 to < 6 years old
干预措施: Amino Acid Solution (Other)
结局指标
主要结局
Pediatric Dosage
时间窗: a. Dosimetry assessments will be performed at multiple timepoints in cycle 1, 2 and 4. - b. Minimum of eight weeks after the first administration of Lutetium Lu 177 edotreotide
Pediatric dosage based on: 1. absorbed dose by target organs (kidney and bone marrow). 2. rate of Dose limitting toxicities - based on adverse event reporting.
次要结局
- Objective Response Rate(At the end of Cycle 2 (each cycle is 28 days))
- PK and dosimetry(Dosimetry assessments will be performed at multiple timepoints at Cycle 1, 2 and 4.)
- Rate of adverse events(From treatment start until 33 days following the last dose of trial treatment or until the End of Last Treatment (EOLT) visit, whichever occurs later..)
- Overall Survival, Progression-Free Survival and Duration of Response(Every 9 ± 3 weeks from enrollment until disease progression or for up to two years, whichever came first.)