Patient case: 45-year-old female with colon cancer; genetic feature: PIK3CA (E545K)

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

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).

Detailed description: 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.

Eligibility: Inclusion Criteria:
  -  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)
  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.

Relevance to patient case: not relevant