A Phase 1/2a Study Utilizing 64Cu-LNTH-1363S (64Cu Radiolabeled FAPi PET/CT Imaging Agent) in Patients With Sarcoma or Gastrointestinal Tract Cancer (PHANTOM Trial)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 26
- 试验地点
- 10
- 主要终点
- Primary Part 1 Biodistribution of 64Cu-LNTH-1363S
研究概览
简要总结
This is a multicenter, open-label, prospective Phase 1/2a study to assess safety and tolerability, establish dosimetry and to identify an optimal imaging dose (radioactivity) and imaging time window of 64Cu-LNTH-1363S, and to compare its imaging biodistribution with FAP expression by IHC in patients with sarcomas or GIT cancers. The study will be conducted in 2 parts (Part 1 and Part 2).
详细描述
Part 1 will determine the biodistribution, dosimetry, optimal dose (radioactivity) and imaging time window of 64Cu-LNTH-1363S in 6 evaluable patients with supposed FAP-expressing solid tumors (metastatic sarcomas). All six patients will receive 8 ± 1 mCi (~90 μg mass dose) in this study. All images will undergo analysis by blinded central readers. Optimal radioactivity and timing window will be determined based on image quality scores and measured tumor-to-background ratio. Part 1 of the study will last approximately 3 weeks for each patient and includes a Screening Period (up to 14 days), a 1-day Intervention Period and a Safety Follow-up Period (7 days post dose).
Part 2 will evaluate 64Cu-LNTH-1363S correlation with FAP expression measured by IHC (SUVmax and SUVmean vs IHC score) in 20 evaluable patients with non-metastatic, operable, supposed FAP-expressing solid tumors (sarcomas, esophageal, gastric, pancreatic, colorectal) planned for surgery within 60 days (from study imaging). If the optimal radioactivity determined from Part 1 is less than 8 ± 1 mCi, the first 6 patients in Part 2 will be used to validate this optimal radioactivity.
Part 2 of the study will last approximately 10 to 11 weeks and includes: a Screening Period (up to 14 days), a 1-day Intervention Period, a 1 day Safety Followup Period (Day 2) and a Scheduled Surgery IHC Sample Collection Period (from Day 2 to Day 60).
Both Part 1 and Part 2 of the study will also monitor cardiac safety by detecting changes in HR, T wave, ST segment and other ECG parameters and characterizing the concentration-response relationship of 64Cu-LNTH-1363S for QT and corrected QT interval (QTc) prolongation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 15 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients are eligible to be included in the study only if all of the following criteria apply:
- •Patient must be ≥ 15 years of age and must have provided written informed consent and assent, where applicable (by patient or legal guardian). Those aged ≥15 to <18 years must weigh at least 55 kg.
- •Patients with suspected FAP-expressing metastatic sarcoma.
- •Patients must have histological, pathological, and/or cytological confirmation of a metastatic sarcoma (e.g., undifferentiated pleomorphic sarcoma, liposarcoma, Leiomyosarcoma, myxofibrosarcoma, solitary fibrous tumor, Ewing's sarcoma, synovial sarcoma, sarcoma not otherwise specified, osteosarcoma).
- •Patients must be willing to consent to provide sufficient and adequate archived tumor tissue samples (formalin fixed, paraffin embedded sample), preferably from a biopsy of a tumor lesion obtained either at the time of or after the diagnosis of disease; if archival tissue sample is unavailable, a new biopsy should be performed on the most accessible lesion(s) to obtain the tumor tissue sample.
- •Adequate renal function as determined by a calculated creatinine clearance ≥ 60 mL/min (Cockcroft Gault equation).
- •Women of childbearing potential (WOCBP) must have a negative beta-human chorionic gonadotropin (β-hCG) test and must not be breastfeeding. WOCBP must agree to use a highly effective method of contraception during the study and for 28 days after the last injection of the study drug.
- •Male subjects who are able to father a child must agree to avoid impregnating a partner, to adhere to a highly effective method of contraception and to not donate sperm during the study and for 28 days after the last injection of the study drug.
- •Inclusion Criteria: Part 2
- •Patient must be ≥ 15 years of age and must have provided written informed consent and assent, where applicable (by patient or legal guardian). Those aged ≥15 to <18 years must weigh at least 55 kg.
- •Patients must have histological, pathological, and/or cytological confirmation of a sarcoma or GIT cancers e.g., esophageal, gastric, pancreatic, colorectal cancer.
- •Patients must have suspected FAP expressing sarcoma or GIT cancers and planned for surgery within 60 days (from study imaging).
- •Patients must be willing to consent to provide sufficient and adequate tumor tissue samples (formalin fixed, paraffin embedded sample), from their planned surgery after participating in study imaging.
- •Adequate renal function as determined by a calculated creatinine clearance ≥ 60 mL/min (Cockcroft Gault equation).
- •Women of childbearing potential (WOCBP) must have a negative beta-human chorionic gonadotropin (β-hCG) test and must not be breastfeeding. WOCBP must agree to use a highly effective method of contraception during the study and for 28 days after the last injection of the study drug.
- •Male subjects who are able to father a child must agree to avoid impregnating a partner, to adhere to a highly effective method of contraception and to not donate sperm during the study and for 28 days after the last injection of the study drug.
排除标准
- •Patients are excluded from the study if any of the following criteria apply:
- •Unlikely to comply with protocol procedures, restrictions and requirements as judged by the Investigator.
- •Known pregnancy or breastfeeding.
- •Any PET scan done within 10 physical half-lives of the PET agent prior to receiving study intervention.
- •Patients participating in another clinical trial at the time of screening for this study.
- •Patients who have had systemic anti-cancer therapy administered in the 14 days prior to IP administration.
- •Has undergone or plans to undergo PET or single-photon emission computerized tomography (SPECT) imaging with any other FAPi imaging agent within 6 months prior to or after participating in this trial.
- •History of QT/QTc interval prolongation, a marked baseline QT/QTc interval prolongation (e.g., repeated demonstration of a QTc interval, calculated with Fridericia's correction, > 450 milliseconds) or taking medication known to cause QT/QTc prolongation.
- •A history of additional risk factors for Torsades de Pointes (e.g., heart failure, hypokalemia, family history of long QT syndrome).
- •Exclusion Criteria: Part 2
- •Patients who have had neoadjuvant anti-cancer therapy administered in the 14 days prior to IP administration.
- •Evidence of metastatic or advanced, inoperable disease.
- •Unlikely to comply with protocol procedures, restrictions and requirements and judged by the investigator to be unsuitable for participation.
- •Known pregnancy or breastfeeding.
- •Any PET scan done within 10 physical half-lives of the PET agent prior to receiving study intervention.
- •Patients participating in another clinical trial at the time of screening for this study.
- •Has undergone or plans to undergo PET or SPECT imaging with any other FAPi imaging agent within 6 months prior to or after participating in this trial.
- •History of QT/QTc interval prolongation, a marked baseline QT/QTc interval prolongation (e.g., repeated demonstration of a QTc interval, calculated with Fridericia's correction, > 450 milliseconds) or taking drugs known to cause QT/QTc prolongation.
- •A history of additional risk factors for Torsades de Pointes (e.g., heart failure, hypokalemia, family history of long QT syndrome
结局指标
主要结局
Primary Part 1 Biodistribution of 64Cu-LNTH-1363S
时间窗: During serial PET/CT scans taken on Day 1 at the following timepoints at 0.5 hour ± 10 minutes, 1 hour ±10 minutes, 2 hours ± 15 minutes, 4 to 6 hours, and 24 hours ± 4 hours post study intervention administration.
Time Activity Curves (TACs) describing percentage of the injected activity versus time will be derived for selected organs and tumor lesions and absorbed radiation doses of 64Cu-LNTH-1363S in critical organs (e.g., kidneys, liver) will be estimated.
Primary Part 1 - Optimal dose (radioactivity) and imaging time window of 64Cu-LNTH-1363S
时间窗: During serial PET/CT scans taken on Day 1 at the following timepoints at 0.5 hour ± 10 minutes, 1 hour ±10 minutes, 2 hours ± 15 minutes, 4 to 6 hours, and 24 hours ± 4 hours post study intervention administration.
Optimal dose (radioactivity) and imaging time window will be determined by using image quality scores from blinded central reviews. Each patient will receive 8 ± 1 mCi of 64Cu-LNTH-1363S. The raw data of each patient PET scan will be re-processed using a computer program to simulate scans of the same patient with lower injected activities (6 mCi and 4 mCi).
Primary Part 2 - Correlation of 64Cu-LNTH-1363S biodistribution with Immunohistochemistry FAP expression
时间窗: Post surgery tissue collection to end of study
Correlation of 64Cu-LNTH-1363S biodistribution with FAP expression by IHC (SUVmean and SUVmax vs IHC score) and compare to circulating FAP in blood as analyzed by ELISA method.
Primary Part 1 Biodistribution of 64Cu-LNTH-1363S
时间窗: During serial PET/CT scans taken on Day 1 at the following timepoints at 0.5 hour ± 10 minutes, 1 hour ±10 minutes, 2 hours ± 15 minutes, 4 to 6 hours, and 24 hours ± 4 hours post study intervention administration.
Time Activity Curves (TACs) describing percentage of the injected activity versus time will be derived for selected organs and tumor lesions and absorbed radiation doses of 64Cu-LNTH-1363S in critical organs (e.g., kidneys, liver) will be estimated.
Primary Part 1 - Optimal dose (radioactivity) and imaging time window of 64Cu-LNTH-1363S
时间窗: During serial PET/CT scans taken on Day 1 at the following timepoints at 0.5 hour ± 10 minutes, 1 hour ±10 minutes, 2 hours ± 15 minutes, 4 to 6 hours, and 24 hours ± 4 hours post study intervention administration.
Optimal dose (radioactivity) and imaging time window will be determined by using image quality scores from blinded central reviews. Each patient will receive 8 ± 1 mCi of 64Cu-LNTH-1363S. The raw data of each patient PET scan will be re-processed using a computer program to simulate scans of the same patient with lower injected activities (6 mCi and 4 mCi).
Primary Part 2 - Correlation of 64Cu-LNTH-1363S biodistribution with Immunohistochemistry FAP expression
时间窗: Post surgery tissue collection to end of study
Correlation of 64Cu-LNTH-1363S biodistribution with FAP expression by IHC (SUVmean and SUVmax vs IHC score) and compare to circulating FAP in blood as analyzed by ELISA method.
次要结局
- Secondary Parts 1 and 2 Safety and Tolerability(Part1: From IP administration until the Day 7 (± 1 day) telephone follow up. Part 2: From time of IP administration to until post-surgery IHC sample collection.)
- Secondary Part 1 and Part 2 Cardiac Safety(Continuous ECG monitoring at Visit 2)
- Secondary Part 2 Validate optimal radioactivity in patients with sarcoma or GIT cancer(From start of Part 2 to 6 patients enrolled with qualifying imaging)
- Secondary Part 1 FAP expression profile of 64Cu-LNTH-1363S in patients with sarcoma(From Day 1 until the end of the Scheduled Surgery: IHC sample collection)