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

NCT ID: NCT02913131

Last Updated: 2022-04-22

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-20
• Study Completion Date: 2021-04-05

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.

Conditions

Prostate Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Part A: Feasibility Run-In

Patients with advanced solid tumor malignancies with at least one liver metastasis will be enrolled with iterative adjustment of coil design to optimize imaging parameters including spatial resolution and signal-to-noise ratio (SNR) of hyperpolarized pyruvate / lactate within the target metastatic lesion(s).

Group Type: EXPERIMENTAL

Pyruvate (13C)

Intervention Type: DRUG

Pyruvate injection followed by an MRI scan.

MRI

Intervention Type: DEVICE

MRI scan following the pyruvate (13c) injection

Part B: Biomarker Cohort

Patients with advanced solid tumor malignancies and the presence of at least one liver metastasis amenable to hyperpolarized C-13 pyruvate metabolic MR imaging who are planning on being treated with agent targeting PI3K/mTOR pathway will be enrolled.

Group Type: EXPERIMENTAL

Pyruvate (13C)

Intervention Type: DRUG

Pyruvate injection followed by an MRI scan.

MRI

Intervention Type: DEVICE

MRI scan following the pyruvate (13c) injection

Interventions

Pyruvate (13C)

Pyruvate injection followed by an MRI scan.

Intervention Type: DRUG

MRI

MRI scan following the pyruvate (13c) injection

Intervention Type: DEVICE

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Rahul Aggarwal

OTHER

Sponsor Role: lead

Responsible Party

Rahul Aggarwal

Assistant Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Rahul Aggarwal, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

University of California, San Francisco

San Francisco, California, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

R01CA183071

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2017-02190

Identifier Type: REGISTRY

Identifier Source: secondary_id

159517

Identifier Type: -

Identifier Source: org_study_id