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

a study on Prostate Cancer Solid Tumor

Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at UCSF
Dates
study started
estimated completion
Principal Investigator
Rahul Aggarwal, MD (ucsf)
Photo of Rahul Aggarwal
Rahul Aggarwal

Description

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).

Official Title

Hyperpolarized C-13 Pyruvate as a Biomarker of PI3K/mTOR Pathway Inhibition in Patients With Advanced Solid Tumor Malignancies

Details

This is a single center prospective imaging study investigating the utility of hyperpolarized C-13 pyruvate/metabolic magnetic resonance (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.

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.

Keywords

Prostate Cancer Prostatic Neoplasms Neoplasms Pyruvate (13C) MRI

Eligibility

You can join if…

Open to people ages 18 years and up

  • 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)

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.

Location

  • University of California, San Francisco accepting new patients
    San Francisco California 94143 United States

Lead Scientist at UC Health

  • Rahul Aggarwal, MD (ucsf)
    I am a Medical Oncologist within the Division of Hematology/Oncology at the University of California San Francisco. My clinical practice focuses on patients with advanced solid tumor malignancies with a particular emphasis on genitourinary malignancies including prostate, kidney, bladder, and testicular cancer. I serve as the Co-Leader for the GU Medical Oncology program at UCSF.

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Rahul Aggarwal
ID
NCT02913131
Phase
Phase 1/2
Study Type
Interventional
Last Updated