This is a single center prospective imaging study investigating the utility of hyperpolarized C-13 pyruvate as a Biomarker of PI3K/mTOR pathway inhibition in patients with advanced solid tumor malignancies. The current protocol will serve as a companion imaging biomarker study paired with therapeutic trials of PI3K/mTOR pathway inhibitors (e.g. CUDC-907, BYL719), as well as a stand-alone protocol for patients treated with standard-of-care therapies inhibiting the PI3K/mTOR signaling pathway (eg. everolimus).
Hyperpolarized C-13 Pyruvate as a Biomarker of PI3K/mTOR Pathway Inhibition in Patients With Advanced Solid Tumor Malignancies
This is a single center prospective imaging study investigating the utility of hyperpolarized C-13 pyruvate/metabolic MR imaging. The current protocol will serve as a companion imaging biomarker study paired with therapeutic trials of PI3K/mTOR pathway inhibitors (e.g. CUDC-907, BYL719), as well as a stand-alone protocol for patients treated with standard-of-care therapies inhibiting the PI3K/mTOR signaling pathway (eg. everolimus).
In Part A (run-in feasibility phase), patients will undergo imaging at a single time point, without paired tumor biopsy. There will be no follow up imaging or requirement for treatment with PI3K/mTOR pathway inhibitor. Iterative adjustment of radiofrequency coil geometry and imaging sequences will be undertaken to optimize intra-tumoral hyperpolarized pyruvate/lactate signal-to-noise ratio with the goal of achieving signal-to-noise ratio of at least 10 in a minimum of 3 patients in order to proceed to Part B of the study.
In part B, patients will undergo paired baseline hyperpolarized C-13 pyruvate imaging + tumor biopsy,then initiate treatment with agent inhibiting the PI3K/mTOR pathway. After 21 days (+/- 14 days), patients will undergo repeat hyperpolarized C-13 pyruvate MR imaging + tumor biopsy. Patients will subsequently be treated with PI3K/mTOR pathway inhibitor until disease progression, unacceptable toxicity, or patient/physician decision to discontinue therapy.
You can join if…
Open to people ages 18 years and up
Presence of at least one target liver lesion detected by standard staging scans that,in the judgment of Study Investigators, would be amenable to hyperpolarized C-13 pyruvate/metabolic MR imaging: Target lesion must measure 1.5 cm in long axis diameter on CT or MRI
The subject 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 organ function, including creatinine < 1.5 x ULN or estimated creatinine clearance 50 mL/min (by the Cockcroft Gault equation) and total bilirubin <3x ULN.
Part B only:
Presence of at least one target lesion amenable to percutaneous tumor biopsy in the judgment of Interventional Radiology
No prior local therapy to target liver lesion.
No history of bleeding diathesis.
Patients on anti-coagulation they must be able to safely stop treatment for purposes of tumor biopsy.
Planned treatment with agent targeting PI3K/mTOR pathway (either standard of care or investigational agent)
You CAN'T join if...
Patients who because of age, general medical or psychiatric condition, or physiologic status cannot give valid informed consent.
Patients unwilling or unable to undergo MR imaging, including patients with contra-indications to MRI, such as cardiac pacemakers or non-compatible intracranial vascular clips.
Metallic implant or device that distorts local magnetic field and compromises the quality of MR imaging.
Poorly controlled hypertension, defined as systolic blood pressure at study entry greater than 160 mm Hg or diastolic blood pressure greater than 100 mm Hg. The addition of anti-hypertensives to control blood pressure is allowed.
Congestive heart failure or New York Heart Association (NYHA) status ≥ 2.
A history of clinically significant EKG abnormalities, including QT prolongation (QTcF
500 ms), a family history of prolonged QT interval syndrome, or myocardial infarction (MI) within 6 months of study entry. Patients with rate-controlled atrial fibrillation/flutter will be allowed on study.
Any condition that, in the opinion of the Principal Investigator, would impair the patient's ability to comply with study procedures.
University of California, San Francisco San Francisco, California, 94158, United States