Hyperpolarized C-13 Pyruvate as a Biomarker in Patients With Advanced Solid Tumor Malignancies

• Status: Terminated
• Trial end date: 2021-04-05
• Target enrollment: 0
• Participant gender: All

Summary

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).

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Rahul Aggarwal
• Collaborators: National Cancer Institute (NCI); National Institutes of Health (NIH)

Criteria

Inclusion Criteria:

• Presence of at least one target liver or other intra-abdominal 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 >=1.0 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 >=500 mL/min (by the Cockcroft Gault equation) and total bilirubin <3x upper limit of normal (ULN).

Part B only:

• No prior local therapy to target lesion.

• If patient agrees to optional biopsy:

• Presence of at least one target lesion amenable to percutaneous tumor biopsy in the judgment of Interventional Radiology

• 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)

Exclusion Criteria:

• 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.