Magnetic Resonance (MR) Imaging With Hyperpolarized Pyruvate (HP) (13C) in Castration-Resistant Prostate Cancer

NCT02911467 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: 155595R01CA166655-04
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective imaging study evaluating the utility of baseline metabolic MR imaging with Hyperpolarized Pyruvate (HP) (13C) as a predictive response biomarker to androgen signaling inhibition in patients with castration-resistant prostate cancer.

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Mean difference in baseline intra-tumoral peak lac/pyr ratio on HP C-13 MRI in ASI-refractory versus ASI-responsive CRPC tumors

  ASI-refractory disease is defined as progression by PCWG2 criteria within 6 months of treatment initiation. ASI-responsive disease includes all other tumors not meeting this criterion. A two sample t-test will be used to compare the mean intra-tumoral HP lac/pyr ratio between treatment-refractory versus treatment-responsive tumors. If a non-parametric distribution is observed, a Mann-Whitney test may also be used to compare the two groups.

  Up to 6 months

Secondary Outcomes (5)

• Association between change from baseline in peak intra-tumoral HP lac/pyr ratio after 28 days of ASI treatment with subsequent clinical outcomes on ASI treatment

  Up to 28 days

• Mean percent change from baseline in peak intra-tumoral HP lac/pyr ratio on repeat metabolic MRI

  Up to 6 months

• Baseline peak intra-tumoral HP lac/pyr ratio cut-point that most accurately predicts for response versus refractoriness to subsequent ASI treatment

  Baseline

• Frequency of clinically significant changes in safety variables over time

  Up to 6 months

• Mean Intra-patient reproducibility of HP lac/pyr ratio

  Up to 6 months

Study Arms (1)

MR imaging with hyperpolarized 13C pyruvate of men with CRPC

EXPERIMENTAL

75 men with castration-resistant prostate cancer (CRPC) will undergo MR imaging with hyperpolarized 13C pyruvate of a pre-selected target lesion at baseline and after 1 month of treatment with an androgen signaling inhibitor. Patients with CRPC that is not primarily refractory (defined as disease progression by PCWG2 criteria within 6 months of treatment initiation) to Androgen Signaling Inhibitors (ASI) treatment will undergo a third metabolic MR scan at the time of disease progression. Patients may undergo optional MR- or CT-guided tumor biopsies at baseline and at the time of disease progression.

Drug: Pyruvate (13C); Device: MRI

Interventions

Pyruvate (13C) DRUG

Pyruvate injection followed by an MRI scan.

Also known as: Hyperpolarized Pyruvate (13C)

MR imaging with hyperpolarized 13C pyruvate of men with CRPC

MRI DEVICE

MRI scan following the Pyruvate injection

Also known as: Magnetic Resonance Imaging

MR imaging with hyperpolarized 13C pyruvate of men with CRPC

Eligibility Criteria

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

You may qualify if:

• Biopsy-proven prostate cancer.
• Progressive, castration-resistant disease according to PCWG2 criteria.
• Planned treatment with an androgen signaling inhibitor (e.g., abiraterone, enzalutamide, apalutamide (ARN-509)). Patients must not be receiving androgen signaling inhibitor at the time of the baseline MR scan. Combination treatment (e.g., androgen signaling inhibitor in conjunction with another systemic treatment) is allowed.
• Presence of at least one target lesion detected by standard staging scans that, in the judgment of Study Investigators, would be amenable to hyperpolarized C-13 pyruvate/metabolic MR imaging:
• Soft tissue/visceral organ target lesions must measure at 1.5 cm in long axis diameter on CT or MRI.
• Target lesions in the bone must be visualized by CT or MRI (lesions present only on bone scan do not qualify).
• For patients with target lesion in prostate/prostatic bed:
• i. No contra-indications to endorectal coil insertion (e.g., patients with a prior abdominoperineal resection of the rectum or latex allergy).
• ii. No prior local treatment to the selected lesion. Patients who have received prior radiation or ablative therapy to the prostate will be required to have biopsy-proven evidence of disease recurrence following completion of local therapy.
• 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 absolute neutrophil count (ANC) ≥ 1500 cells/µL, hemoglobin ≥ 9.0 gm/dL, platelets ≥ 75,000 cells/µL, creatinine \< 1.5 x ULN or estimated creatinine clearance ≥ 50 mL/min (by the Cockcroft Gault equation), bilirubin \<1.5x ULN (unless Gilbert's is suspected in which case total bilirubin \< 3 x ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 1.5x ULN.
• For patients undergoing optional tumor biopsy:
• No history of bleeding diathesis.
• Patients on anti-coagulation they must be able to safely stop treatment for purposes of tumor biopsy.

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 hip implant or any other 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 Cancer Institute (NCI): collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94158, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Pyruvic Acid; Magnetic Resonance Imaging

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; Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• Rahul Aggarwal, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Rahul Aggarwal, MD

Study Record Dates

• First Submitted: September 19, 2016
• First Posted: September 22, 2016
• Study Start: November 8, 2016
• Primary Completion: July 20, 2020
• Study Completion: July 20, 2020
• Last Updated: July 24, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)