Hyperpolarized 13C MRI as a Biomarker in Advanced Solid Tumors

Официальное название

A Phase I/II Study of Hyperpolarized 13C MRI as a Biomarker of Aggressiveness & Response to Therapy in Patients With Advanced Solid Tumors

Обзор

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.

Подробное описание

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

SECONDARY OBJECTIVES:

Phase I/Part A

1. To further characterize the safety profile of hyperpolarized 13C-pyruvate +/- 13C,15N-urea. 2. To determine the reproducibility of intra-tumoral HP lac/pyr ratio with same-day repeated dose studies.

Phase II/Part B

1. To study the association between clinical outcomes and the percent change from baseline in peak intra-tumoral hyperpolarized lactate-to pyruvate ratio and kPL (+/-correction for HP urea AUC) after initiation of SOC treatment. 2. To further characterize the safety profile of hyperpolarized 13C pyruvate +/- 13C,15N-urea. 3. To determine the reproducibility of intra-tumoral HP lac/pyr ratio and/or HP urea AUC with same-day repeated dose studies.

OUTLINE:

Participants will be enrolled in Part A which is the feasibility, run-in study which includes the iterative adjustment of coil design to optimize imaging parameters within the target tumor lesion(s). If the data from Part A supports further investigation, additional participants will be enrolled in Part B which is a biomarker cohort which includes participants who are planning on being treated with either standard-of-care (SOC) or investigational therapies and will be followed until discontinuation of the treatment regimen outside of this protocol.

Вмешательства

• Препарат Hyperpolarized 13C-Pyruvate
  Given IV
• Процедура Magnetic Resonance Imaging (MRI)
  Imaging procedure
• Препарат 13C,15N-Urea
  Given IV

Первичные конечные точки

• Signal-to-noise ratio (Part A) [Срок оценки: Day of imaging (1 day)]
• Mean percent change from baseline in intratumoral HP pyruvate/lactate ratio [Срок оценки: Up to 25 days]
• Mean percent change from baseline in Urea Area Under Curve (AUC) [Срок оценки: Up to 25 days]

Вторичные конечные точки (8)

• Number of participants reporting adverse events (Part A) [Срок оценки: Day of imaging (1 day)]
• Number of participants reporting adverse events (Part B) [Срок оценки: Up to 6 months]
• Median percent change from baseline in peak intratumoral hyperpolarized lactate-to-pyruvate ratio (Part B) [Срок оценки: Up to 6 months]
• Median percent change from baseline in intra-tumoral HP Urea AUC (Part B) [Срок оценки: Up to 6 months]
• Objective response rate (ORR) (Part B) [Срок оценки: Up to 6 months]
• Clinical benefit rate (CBR) (Part B) [Срок оценки: Up to 6 months]
• Radiographic progression-free survival (rPFS) (Part B) [Срок оценки: Up to 6 months]
• Lactate/pyruvate ratio (Part B) [Срок оценки: 1 day]

Критерии участия

Критерии включения

• 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 1.
• 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.

Критерии исключения

• 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 >= 2.
• 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,

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• University of California, San Francisco — San Francisco

Идентификаторы

NCT: NCT05599048 · 22924 · NCI-2022-09149 · P41EB013598-11 · 5U01EB026412-04 · 5R01CA256740-02

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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