Overview

This trial is active, not recruiting.

Condition prostate cancer
Treatments pyruvate (13c), mri
Phase phase 1
Sponsor Rahul Aggarwal
Collaborator National Institutes of Health (NIH)
Start date December 2015
End date October 2018
Trial size 40 participants
Trial identifier NCT02913131, 159517, R01CA183071

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).

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose diagnostic
Arm
(Experimental)
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). The target SNR of 10 must be achieved in at least 3 patients in order to proceed to part B of the study.
pyruvate (13c)
Pyruvate injection followed by an MRI scan.
mri
MRI scan following the pyruvate (13c) injection
(Experimental)
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.
pyruvate (13c)
Pyruvate injection followed by an MRI scan.
mri
MRI scan following the pyruvate (13c) injection

Primary Outcomes

Measure
Part A: Signal-to-noise ratio with respect to intra-tumoral hyperpolarized C-13 lac/pyr ratio detected within target liver metastasis in patients with advanced solid tumor malignancies.
time frame: Baseline
Part B: Mean percent change from baseline in peak intra-tumoral hyperpolarized lactate/pyruvate ratio after initiation of treatment with PI3K/mTOR pathway inhibitor.
time frame: Baseline and after approximately 21 days of therapy. Follow-up for approximately 6 months

Secondary Outcomes

Measure
Frequency of adverse events as graded by Common Toxicity Criteria version 4.0
time frame: Throughout study - from baseline, after 21 days of therapy, and for duration of follow-up (approximately 6 months)
Association between percent change from baseline in peak intra-tumoral HP lactate/pyruvate ratio on metabolic MR imaging with clinical benefit rate (Part B)
time frame: From baseline to approximately 21 days of therapy. Follow-up for approximately 6 months
Association between percent change from baseline in peak intra-humoral HP lactrate/pyruvate ratio on metabolic MR imaging with progression-free survival (Part B)
time frame: From baseline to approximately 21 days of therapy. Follow-up for approximately 6 months

Eligibility Criteria

Male or female participants at least 18 years old.

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.

Additional Information

Official title Hyperpolarized C-13 Pyruvate as a Biomarker of PI3K/mTOR Pathway Inhibition in Patients With Advanced Solid Tumor Malignancies
Principal investigator Rahul Aggarwal, MD
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.
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by University of California, San Francisco.