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

NCT02913131 | Terminated Phase 1 Results DMC FDA Drug

• 3 other identifiers: 159517R01CA183071NCI-2017-02190
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

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).

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (2)

• Signal-to-noise Ratio (Part A)

  The Signal-to-noise ratio with respect to intra-tumoral hyperpolarized (HP) C-13 Lactate/Pyruvate (lac/pyr) ratio detected within target liver or other intra-abdominal metastasis in patients with advanced solid tumor malignancies enrolled in the feasibility cohort will be determined

  1 day

• Mean Percent Change From Baseline in Peak Intra-tumoral Hyperpolarized Lactate/Pyruvate Ratio (Part B)

  Descriptive statistics will be used to characterize the mean change from baseline in intra-tumoral HP pyruvate/lactate ratio after initiation of treatment with PI3K/mTOR pathway inhibitor for participants enrolled in the biomarker cohort, along with 95% confidence interval.

  Up to 24 months

Secondary Outcomes (3)

• Number of Participants With Reported Treatment-related Adverse Events

  Up to 24 months

• Association Between Percent Change From Baseline in Peak Intra-tumoral Hyperpolarized Lactate/Pyruvate Ratio on Metabolic MR Imaging With Clinical Benefit Rate (Part B)

  Up to 24 months

• Association Between Percent Change From Baseline in Peak Intra-humoral HP Lactate/Pyruvate Ratio on Metabolic MR Imaging With Progression-free Survival (Part B)

  Up to 24 months

Study Arms (2)

Part A: Feasibility Run-In

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).

Drug: Pyruvate (13C); Device: MRI

Part B: Biomarker Cohort

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.

Drug: Pyruvate (13C); Device: MRI

Interventions

Pyruvate (13C) DRUG

Pyruvate injection followed by an MRI scan.

Part A: Feasibility Run-In; Part B: Biomarker Cohort

MRI DEVICE

MRI scan following the pyruvate (13c) injection

Part A: Feasibility Run-In; Part B: Biomarker Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 may not qualify 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.

Sponsors & Collaborators

• Rahul Aggarwal: lead
• National Institutes of Health (NIH): collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Pyruvic Acid

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pyruvates; Keto Acids; Carboxylic Acids; Organic Chemicals

Limitations and Caveats

The study was closed earlier than expected due to low enrollment in both cohorts.

Results Point of Contact

• Title: Dr. Rahul Aggarwal, MD
• Organization: University of California, San Francisco

Rahul.Aggarwal@ucsf.edu

(415) 353-9278

Study Officials

• Rahul Aggarwal, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: September 20, 2016
• First Posted: September 23, 2016
• Study Start: October 20, 2016
• Primary Completion: April 5, 2021
• Study Completion: April 5, 2021
• Last Updated: April 22, 2022
• Results First Posted: April 22, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)