A Phase I/II Study of Hyperpolarized 13C MRI as a Biomarker of Aggressiveness & Response to Therapy in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 65
- 试验地点
- 2
- 主要终点
- Signal-to-noise ratio (Part A)
研究概览
简要总结
This is a single center prospective imaging study investigating the utility of hyperpolarized 13C-pyruvate +/-13C,15N-Urea/ metabolic MR imaging. The current protocol will serve as a companion imaging biomarker study paired with standard of care (SOC) therapeutics, as well as investigational therapies that participants may be scheduled to receive outside of this protocol.
详细描述
PRIMARY OBJECTIVES:
Phase I/Part A
1. To optimize the signal-to-noise ratio in detecting intra-tumoral hyperpolarized 13C pyruvate/lactate signal and hyperpolarized urea area under the curve (AUC) using metabolic magnetic resonance (MR) imaging in patients with advanced solid tumors.
Phase II/Part B
1. To determine the mean percent change from baseline in peak intra-tumoral hyperpolarized lactate-to-pyruvate ratio,pyruvate-to-lactate kinetic constant (kPL) and urea AUC after initiation of usual care/standard of care (SOC) treatment
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Presence of at least one target pelvic, abdominal, thoracic, neck or extremity lesion detected by standard staging scans that, in the judgment of study investigator, would be amenable to hyperpolarized C-13 pyruvate/metabolic MR imaging:
- •a. Target lesion must measure at least 1.0 cm in long axis diameter on Computerized tomography (CT) or magnetic resonance imaging (MRI).
- •The participant is able and willing to comply with study procedures and provide signed and dated informed consent.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or
- •Adequate renal function defined as creatinine < 1.5 x upper limit of normal (ULN) or estimated creatinine clearance >50 mL/min (by the Cockcroft Gault equation).
- •Participants age 18 and older.
- •Part B only:
- •Planned treatment for disease with either standard of care regimen or an investigational agent.
排除标准
- •Patients who because of age, general medical or psychiatric condition, or physiologic status cannot give valid informed consent.
- •Patients with contra- indications to MRI, such as cardiac pacemakers or non-compatible intracranial vascular clips.
- •Patients with a metallic implant or device that distorts local magnetic field and compromises the quality of MR imaging.
- •Patients with poorly controlled hypertension, defined as systolic blood pressure at study entry greater than 160mm Hg or diastolic blood pressure greater than 100mm Hg.
- •Note: The addition of anti-hypertensives to control blood pressure is allowed.
- •Patients with congestive heart failure or New York Heart Association (NYHA) status >=
- •Patients who are pregnant or lactating.
- •A history of clinically significant EKG abnormalities or myocardial infarction (MI) within 6 months of study entry.
- •Note: Patients with rate-controlled atrial fibrillation/flutter will be allowed on study.
- •Any condition that, in the opinion of the Principal Investigator,
研究组 & 干预措施
Part A / Phase 1: Feasibility Run-In
Participants will undergo MR imaging at a single time point. Imaging will take one day and no follow up is planned.
干预措施: Hyperpolarized 13C-Pyruvate (Drug)
Part A / Phase 1: Feasibility Run-In
Participants will undergo MR imaging at a single time point. Imaging will take one day and no follow up is planned.
干预措施: Magnetic Resonance Imaging (MRI) (Procedure)
Part A / Phase 1: Feasibility Run-In
Participants will undergo MR imaging at a single time point. Imaging will take one day and no follow up is planned.
干预措施: 13C,15N-Urea (Drug)
Part B/ Phase II: Biomarker Cohort
Participants will undergo paired 13C-pyruvate +/- 13C,15N-urea/metabolic MR imaging at baseline and again after approximately 21 days of therapy. Duration of the intervention period is approximately 21 days, and participants will be followed until discontinuation of their current SOC treatment regimen, about 6 months.
干预措施: Hyperpolarized 13C-Pyruvate (Drug)
Part B/ Phase II: Biomarker Cohort
Participants will undergo paired 13C-pyruvate +/- 13C,15N-urea/metabolic MR imaging at baseline and again after approximately 21 days of therapy. Duration of the intervention period is approximately 21 days, and participants will be followed until discontinuation of their current SOC treatment regimen, about 6 months.
干预措施: Magnetic Resonance Imaging (MRI) (Procedure)
Part B/ Phase II: Biomarker Cohort
Participants will undergo paired 13C-pyruvate +/- 13C,15N-urea/metabolic MR imaging at baseline and again after approximately 21 days of therapy. Duration of the intervention period is approximately 21 days, and participants will be followed until discontinuation of their current SOC treatment regimen, about 6 months.
干预措施: 13C,15N-Urea (Drug)
结局指标
主要结局
Signal-to-noise ratio (Part A)
时间窗: Day of imaging (1 day)
Signal-to-noise ratios is defined as a MR/spectroscopy parameter, consisting of the HP C13-Pyruvate or Lactate signal (peak) relative to background noise level (baseline) in MRI spectra of the tissue. For the analysis and interpretation of the HP 13C-pyruvate MR imaging data, DICOM software package (SIVIC) will be used to align, display and quantitatively interrogate serial multi-parametric imaging data.
Mean percent change from baseline in intratumoral HP pyruvate/lactate ratio
时间窗: Up to 25 days
Intra-tumoral region of interest (ROI) will be used to quantify peak HP lactate/pyruvate ratio values in the selected volumes of interest. Descriptive statistics will be used to characterize the mean change from baseline in intra-tumoral HP pyruvate/lactate ratio for the study cohort, along with a 95% confidence interval
Mean percent change from baseline in Urea Area Under Curve (AUC)
时间窗: Up to 25 days
Intra-tumoral region of interest (ROI) will be used to quantify urea AUC. Descriptive statistics will be used to characterize the mean change from baseline in Urea Area Under Curve (AUC)
次要结局
- Number of participants reporting adverse events (Part A)(Day of imaging (1 day))
- Number of participants reporting adverse events (Part B)(Up to 6 months)
- Median percent change from baseline in peak intratumoral hyperpolarized lactate-to-pyruvate ratio (Part B)(Up to 6 months)
- Median percent change from baseline in intra-tumoral HP Urea AUC (Part B)(Up to 6 months)
- Objective response rate (ORR) (Part B)(Up to 6 months)
- Clinical benefit rate (CBR) (Part B)(Up to 6 months)
- Radiographic progression-free survival (rPFS) (Part B)(Up to 6 months)
- Lactate/pyruvate ratio (Part B)(1 day)
研究者
Robert Bok, MD, PhD
Principal Investigator
University of California, San Francisco