Clinical trial NCT02913131: Hyperpolarized C-13 Pyruvate as a Biomarker in Patients With Advanced Solid Tumor Malignancies
Official title: Hyperpolarized C-13 Pyruvate as a Biomarker of PI3K/mTOR Pathway Inhibition in Patients With Advanced Solid Tumor Malignancies
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Prostate Cancer
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Cancer Institute (NCI)
First posted: 2016-09-23
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: DIAGNOSTIC

Brief 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 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.

Eligibility 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.

Primary outcomes:
measure: Signal-to-noise Ratio (Part A)
timeFrame: 1 day
measure: Mean Percent Change From Baseline in Peak Intra-tumoral Hyperpolarized Lactate/Pyruvate Ratio (Part B)
timeFrame: Up to 24 months
Secondary outcomes:
measure: Number of Participants With Reported Treatment-related Adverse Events
timeFrame: Up to 24 months
measure: Association Between Percent Change From Baseline in Peak Intra-tumoral Hyperpolarized Lactate/Pyruvate Ratio on Metabolic MR Imaging With Clinical Benefit Rate (Part B)
timeFrame: Up to 24 months
measure: Association Between Percent Change From Baseline in Peak Intra-humoral HP Lactate/Pyruvate Ratio on Metabolic MR Imaging With Progression-free Survival (Part B)
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
Study officials:
affiliation: University of California, San Francisco
name: Rahul Aggarwal, MD
role: PRINCIPAL_INVESTIGATOR
References: