177Lu-DOTATATE Modified Delivery Based on Individualized Dosimetry
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Objective Response Rate (ORR) at 6 months after treatment
研究概览
简要总结
The goal of this study is to learn if individualized dosimetry-based prescribing of Lutetium-177 DOTATATE (Lutathera, Novartis Pharmaceuticals) improves treatment outcomes for adults with unresectable neuroendocrine tumors. To investigate this, study participants will:
- Undergo Somatostatin Receptor (SSTR) positron emission tomography (PET) imaging, such as a DOTATOC PET/CT scan
- Be randomized to receive standard treatment (as per FDA guidelines) or investigational treatment (customized dosing of Lutathera based upon dosimetry)
- Undergo blood tests for 4 to 8 weeks after each Lutathera treatment
- Complete patient reported outcome questionnaires
- Visit the clinic for follow-up about every 8 weeks.
详细描述
This is a randomized controlled clinical trial evaluating the impact of forward planning dosimetry for Lutetium-177 DOTATATE (Lutathera, Novartis Pharmaceuticals), a radiopharmaceutical approved to treat neuroendocrine tumors by the U.S. FDA.
If a patient consents to participate, and is deemed eligible to move forward, there is a 2 out of 3 chance to receive the investigational treatment (the Lutathera treatment customized to tumor uptake and kidney uptake). The standard treatment is 200 millicuries (mCi) of Lutathera per cycle, with potential adjustments for safety per the FDA-approved package insert.
Regardless of the assigned group (investigational treatment or standard treatment), the first treatment is 200 mCi. This is given with amino acids, which is required for this treatment.
Participants in the standard treatment continue to receive 200 mCi per treatment, with or without adjustment based on package insert instructions, for up to 4 treatments total.
Participants in the investigational treatment will receive a customized dose of Lutathera, up to 400 mCi per treatment for treatments 2 - 4, in the hopes that escalation will be safe and effective in many patients based on individualized dosimetry.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provision of signed and dated informed consent form.
- •Stated willingness to comply with all study procedures and availability for the duration of the study.
- •Aged ≥ 18 years at time of consent.
- •Pathologically confirmed (histology or cytology) malignant neoplasm that is determined to be a well-differentiated neuroendocrine tumor (Ki-67 ≤ 20%) with the primary tumor location known or believed to be gastroenteropancreatic origin (GEP-NET)
- •Disease measuring ≥ 1.5 cm in diameter on CT or MRI as measured per RECIST that shows uptake > liver background on sstr2 PET/CT with any FDA approved sstr2 imaging agent. SSTR2 PET/CT must have been obtained within 90 days prior to scheduled C1D1 of Lutathera.
- •Recommended to receive LUTATHERA® therapy for unresectable and/or metastatic neuroendocrine disease.
- •Adequate performance status (ECOG of 0 or 1; or Karnofsky performance status of ≥70).
- •Agrees to contraception during therapy.
- •Neutrophil count within normal limits within 28 days of treatment day
- •Platelet count within normal limits within 28 days of treatment day
- •Ability to take oral medication and be willing to adhere to the treatment regimen
- •For individuals of reproductive potential: agreement to use effective birth control
- •Agreement to adhere to Lifestyle Considerations throughout study duration: abstain from caffeine or xanthine-containing products as well as alcohol before the start of cycle dosing and through the cycle's final blood sample; minimize social interactions during low blood counts.
排除标准
- •Individuals who are pregnant or lactating (note: potential participants should not engage in 'pump & dump' strategy; lactation must be discontinued).
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (requiring inpatient admission or a delay to start of therapy), fever, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Surgery, radiation therapy, or chemotherapy ≤ 4 weeks of C1D1 (Toxicities from prior therapies should have resolved to ≤ CTCAE grade 1 or a new baseline established).
- •Prior peptide-receptor radiotherapy (PRRT).
- •Therapeutic investigational drug within 4 weeks of C1D1 (imaging agents are acceptable).
- •A concurrent malignancy that, in the opinion of the investigator, would cause a safety risk by delaying therapy or confound/negatively impact study objectives (documentation of the rationale must be provided)
- •Prior external beam radiation dose to the kidneys of >10 Gy (mean dose to functional renal volume).
- •Prior external beam radiation (including brachytherapy) involving 25% of the bone marrow (excluding scatter doses of ≤ 5 Gy) as estimated by a radiation oncologist.
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to Octreoscan® or Netspot™.
研究组 & 干预措施
Dosimetry-based lutetium Lu 177 dotatate therapy
Intravenous administration of lutetium Lu 177 dotatate once every 8 weeks for up to 4 total cycles.
Intended administered radioactivity:
Cycle 1: 200 millicuries (mCi) Cycles 2, 3, and 4: based upon dosimetry for radiation exposure to bone marrow (no more than 1 Gy per administration) and kidneys (maximum dose 28 Gy total). Not to exceed 400 millicuries (mCi) per cycle (1400 mCi maximum for all cycles).
干预措施: Lutetium Lu 177 dotatate therapy (Drug)
Standard lutetium Lu 177 dotatate
Intravenous administration of lutetium Lu 177 dotatate once every 8 weeks for up to 4 total cycles. Each cycle is intended to receive 200 millicuries of radioactivity for a total treatment of 800 millicuries.
干预措施: Lutetium Lu 177 dotatate therapy (Drug)
结局指标
主要结局
Objective Response Rate (ORR) at 6 months after treatment
时间窗: 6 months after completion of treatment
Determine objective response rate in patients with grade 1 or 2 gastroenteropancreatic neuroendocrine tumors (GEP-NET) treated with dosimetrically-determined LUTATHERA administration compared to active control.
次要结局
- Correlation of hematologic toxicities(At 6 months post-treatment)
- Treatment emergent toxicity assessment(From treatment day 1 every 6 months for 5 years post-treatment)
- Time to disease progression(Up to 5 years post-treatment)
研究者
Stephen A. Graves
Assistant Professor
University of Iowa