Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

All Drugs and Chemicals

Anti-Infective Agents

Other Dietary Supplements

Hormones

Carbamide Peroxide

Hormone Antagonists

Pyruvate

Participants will undergo Hyperpolarized 13C-Pyruvate +/- 13C,15N-Urea imaging as part of a multi-parametric magnetic resonance imaging (mpMRI) exam, with the primary objective of optimizing imaging sequences and techniques to maximize signal-to-noise ratio of imaging modality.

Participants with pre-planned, non-interventional stereotactic body radiotherapy (SBRT) will undergo an HP Pyruvate +/-Urea mpMRI exam at baseline, at 3 months post-SBRT treatment and at 1yr post-treatment.

Participants with with high-risk localized prostate cancer and have pre-planned, non-interventional primary radiation therapy (RT) with concurrent, systemic, non-interventional hormone therapy will undergo HP Pyruvate+/-Urea mpMRI at baseline prior to the start of systemic hormone therapy, 4-12 weeks after the initiation of systemic hormone therapy (prior to radiation therapy), at 3 months post-radiation therapy, and at +1yr post-radiation therapy.

Evaluable SBRT participants who undergo HP Pyruvate +/-Urea mpMRI at time of biochemical failure, followed by magnetic resonance (MR) / ultrasound (US) fusion-guided prostate biopsy within 12 weeks following baseline MR exam. Participants in this group have the option of undergoing a follow up HP Pyruvate +/-Urea MR exam 6-15 months following the baseline scan, to evaluate for any interval change.

hyperpolarized pyruvate +/-urea (13C/15N)

Stereotactic body radiotherapy given outside of this study

Non-investigational Stereotactic body radiotherapy (SBRT)

Radiation therapy given outside of this study

Radiotherapy (RT)

Multi-parametric magnetic resonance imaging (mpMRI)

Therapy given outside of this study as part of standard of care

Non-interventional hormone therapy

Biopsies may be taken from Trans-rectal ultrasound (TRUS) -visible lesion at the urologist's discretion

Prostate Biopsy

Louise Magat

Robert Bok, MD, PhD

Anthony Wong, MD, PhD

This is a Phase 2 clinical study of hyperpolarized (HP) 13C-pyruvate (13C), 15N-urea (13C,15N) metabolic MR imaging in prostate cancer patients who are undergoing or have received radiation therapy for prostate cancer.

PRIMARY OBJECTIVES:

I. Part 1: To Optimize the imaging sequences that maximize signal-to-noise ratio (SNR) and intra-tumoral kPL and kPG in regions of tumor vs. adjacent benign tissue as assessed by mpMRI imaging characteristics.

II. Part 2A To perform HP 13C-MRI and measure the changes in tumoral kPL and kPG.

III. Part 2B: To perform HP 13C-MRI and study the metabolic effects (changes in tumor kPL and kPG).

IV. Part 3: To perform HP 13C-MRI at time of Biochemical Failure and measure tumoral kPL and kPG, in previously SBRT treated patients.

SECONDARY OBJECTIVES:

I. To evaluate the intra-patient variability in intra-tumoral kPL and kPG with repeated dose studies (Part 1, 2 \& 3).

II. To determine the association between peak intra-tumoral kPL observed on baseline imaging with serum PSA. (Part 2 \& 3).

III. To determine the association between changes in intra-tumor kPL after 4-12 weeks of systemic hormone therapy and PSA response (Part 2B).

IV. To compare and contrast intra-tumoral kPL and kPG with Prostate Imaging Reporting and Data System (PI-RADS) version 2 and individual mpMRI parameters including apparent diffusion coefficient (ADC) on diffusion-weighted imaging (Part 1, 2 \& 3).

V. To describe the frequency of up-grading of tumor with MR/US-guided fusion biopsy obtained following baseline HP-MRI exam. (Part 3).

VI. To further characterize the safety profile of HP C-13 pyruvate injections (Part 1, 2 \& 3).

VII. For patients imaged with HP 13C-MRI at time of biochemical failure post-SBRT, correlate peak intra-tumoral kPL and kPG with radiotherapy dose distributions from SBRT course (Part 3).

VIII. For studies incorporating HP 13C-urea, the baseline and the on-treatment changes in ureaAUC parameter will be measured and compared to kPL endpoints of the same lesions (Part 1, 2 \& 3).

OUTLINE:

The study is divided into 3 parts. Part 1: Participants undergo imaging as part of a multi-parametric magnetic resonance imaging (mpMRI) exam to determine exact parameters for imaging.

Part 2A: Participants planned for stereotactic body radiotherapy (SBRT) Part 2B: Participants with high-risk localized prostate cancer planned to receive primary radiation therapy with concurrent systemic hormone therapy Part 3: Evaluable SBRT participants scanned at time of biochemical failure and MR/US fusion-guided prostate biopsy within 12 weeks. Participants have the option of undergoing a follow up HP Pyruvate +/- Urea MR exam 6-15 months following the baseline scan.

All participants will receive a scan at baseline and other procedures may be performed as part of routine, non-interventional standard of care at the time of biochemical failure, including serial prostate-specific antigen (PSA) monitoring and gene expression profiling of tumor tissue. Participants will be followed for 24 months after last procedure or removal from study, or until death, whichever occurs first.

Magnetic Resonance (MR) Imaging With Hyperpolarized 13C-Pyruvate +/- 13C,15N-Urea in Patients With Prostate Cancer

A Phase 2 Study of Magnetic Resonance (MR) Imaging With Hyperpolarized 13C-Pyruvate +/- 13C,15N-Urea in Patients With Prostate Cancer Undergoing Radiation Therapy

A signal-to-noise ratio is defined as a MR/spectroscopy parameter, consisting of the HP C13-Pyruvate or Lactate signal (peak) relative to background noise level (baseline) in MRI spectra of the tissue.

The mean percent change in tumoral kPL between baseline and 1-year post-SBRT will be reported.

The mean percent change in tumoral kPG between baseline and 1-year post-SBRT will be reported.

Mean percent change in tumoral kPL for participants receiving systemic hormone therapy between baseline and 1 -year post-SBRT will be reported.

Mean percent change in tumoral kPG for participants receiving systemic hormone therapy between baseline and 1 -year post-SBRT will be reported.

The mean kPL for participants with biochemical failure will be reported.

The mean kPG for participants with biochemical failure will be reported.

Intra-patient variability in the kPL will be summarized by the intraclass correlation and presented with a 90% confidence interval when multiple HP-MRI scans are obtained for a participant.

Intra-patient variability in the kPG will be summarized by the intraclass correlation and presented with a 90% confidence interval when multiple HP-MRI scans are obtained for a participant.

The study cohort will be dichotomized by mean intra-tumoral kPL obtained at baseline with median serum PSA and will be compared between the two dichotomized subgroups using Mann-Whitney test.

Spearman's rank order correlation coefficient will be used to determine the relationship between kPL with PI-RADS version 2 classification score (1 through 5; PI-RADS 1 - Very low (clinically significant cancer is highly unlikely to be present) PI-RADS 2 - Low (clinically significant cancer is unlikely to be present)). The Spearman's correlation coefficient (rs) measures the strength and direction of association between two variables. The Spearman correlation coefficient, rs, can take values from +1 to -1 where a value of +1 indicates a perfect association, an rs of 0 indicates no association and an rs of -1 indicates a perfect negative association. The closer rs is to 0, the weaker the association.

A secondary endpoint will be to identify concordant mismatch of low HP 13C-urea perfusion (ureaAUC) in lesions assessed for kPL.

For the subset of participants who undergo optional follow up MR scan following baseline MRI, the mean percent change from baseline in kPL will be descriptively reported using summary statistics.

The incidence of adverse events as graded by Common Toxicity Criteria version 5.0 will be determined

National Cancer Institute (NCI)

Principal Investigator

Symptoms and General Pathology

Nervous System Diseases

Heart and Blood Diseases

Diseases and Abnormalities at or Before Birth

Skin and Connective Tissue Diseases

Rare Diseases

Syndrome

Von Hippel-Lindau Disease

Neurocutaneous Syndromes

Angiomatosis

Vascular Diseases

Ciliopathies

Congenital Abnormalities

Abnormalities, Multiple

Genetic Diseases, Inborn

Naris Nilubol, M.D.

Von Hippel-Lindau disease (VHL) is an inherited cancer syndrome. Patients are at risk for developing pancreatic cysts and tumors. These tumors are more aggressive in some people than in others. To learn more about this disease, its genetic cause and how best to treat it, this study will 1) identify patients with VHL who have pancreatic lesions; 2) examine the characteristics of the lesions and how fast they grow; 3) study how well imaging tests can reveal lesion characteristics that will help in diagnosis; and 4) perform genetic studies using blood and, when possible, tissue samples.

Patients 12 years of age and older with VHL involving the pancreas may be eligible for this study. Participants will undergo some or all of the following tests and procedures:

* Interviews with a cancer doctor, cancer nurses, and a surgeon (if surgery is recommended).
* Computed tomography (CT) scan of the abdomen, chest, or pelvis. This test uses x-rays to produce images of body tissues and organs in small sections.
* Magnetic resonance imaging (MRI) of the abdomen. This test uses radio waves and a strong magnetic field to produce images of body tissues and organs.
* Ultrasound of the abdomen. This test uses sound waves to create images body tissues and organs.
* Blood tests for routine laboratory chemistries, for tests specific to the pancreas, and for genetic studies
* 24-hour urine studies

After the tests are completed, the doctor will discuss the results with the patient. Patients with a pancreatic tumor that requires surgery will be offered the option of an operation to remove as much tumor as possible. Patients with lesions that are not appropriate for surgery will be asked to return to National Institutes of Health (NIH) for scans and x-rays every year to monitor growth of the lesions. If surgery should become advisable in the future, the option will be discussed at that time. Patients with pancreatic cysts will be asked to return to NIH every 2 years for scans and x-rays to monitor their condition.

Background:

Patients with the familial cancer syndrome von Hippel-Lindau (VHL) demonstrate manifestations in a variety of organs among them the pancreas. Pancreatic manifestations can range from benign cysts and micro cystic adenomas to neuroendocrine tumors of the pancreas which are capable of regional and distant spread. These neuroendocrine tumors can result in life-threatening complications.

This protocol is designed to identify VHL patients with pancreatic manifestations and to follow these patients with serial imaging studies and germ line and tissue genetic analysis.

Objectives:

To identify patients with VHL having pancreatic lesions defined by simple cysts, microcystic adenomas, neuroendocrine tumors and other solid lesions of the pancreas.

To follow patients with VHL and pancreatic manifestations by serial examination with non-invasive imaging studies.

For patients with solid lesions of the pancreas, to determine the rate of growth and to correlate the growth rate with clinical measures of disease progression.

To validate non-invasive imaging methods for differentiating benign solid lesions from lesions with malignant potential.

To characterize the time from initial presentation with pancreatic tumors to the time that surgery is recommended.

Eligibility:

Patients greater than or equal to 12 years of age who have been diagnosed with VHL.

Patients/parent must be able to sign an informed consent and be willing to return to National Institutes of Health (NIH) for follow-up.

Design:

Demographic data will be collected from the medical record and patient interview for each patient participant. Data will be securely stored in a computerized database.

Patients will be evaluated by the Urologic Oncology Branch personnel as indicated to rule out or manage other manifestations of VHL. Imaging studies of regions other than the chest and abdomen will be dictated by best clinical practice for the workup and management of VHL manifestations as has been previously published.

All patients enrolled on this study will be offered genetic counseling by a trained genetic counselor.

After their initial on-study evaluation, patients who are not found to have solid lesions of the pancreas but rather have only cystic disease of the pancreas, will be re-screened every two years with non-invasive imaging studies.

Surgical resection of solid lesions of the pancreas will be recommended based on previously published criteria.

Based on our analysis of likelihood of tumor growth or risk of metastasis, data will be analyzed every two years and appropriate revisions will be made to the surgical management guidelines, if indicated by data analysis.

Projected accrual will be 25 patients per year for a total of 15 years. Thus, we anticipate accruing 600 patients on this protocol.

Natural History and Management of Pancreatic Lesions in Von Hippel-Lindau Disease

Evaluation of the Natural History and Management of Pancreatic Lesions Associated With Von Hippel-Lindau

Pancreatic lesions defined by simple cysts, microcystic adenomas, neuroendocrine tumors and other solid lesions of the pancreas were evaluated by 18F Fludeoxyglucose (18F-FDG-PET) imaging to determine if the participant developed metastatic disease (e.g. tumor spreads to different organs).

Percentage of patients by the location of germline VHL mutations.

Count of participants from which we obtained tissue from pancreatic tumor and normal tissue (when applicable) for Deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and proteins extraction.

Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Count of participants by the type of Von Hippel-Lindau (VHL) gene mutations.

Because this is natural history protocol, deaths or complications from treatments were not considered as AE or SAE. However, because 22 deaths are noted in the mortality module, 22 deaths are also noted in the SAEs per the Results Data Elements Definitions which state that "SAEs include AEs that result in death. Typically, the event(s) leading to death is listed as an AE Term in the SAE table and the number of participants who died due to any cause are reported in the All-Cause Mortality table."

Von Hippel-Lindau disease (VHL) is an inherited cancer syndrome. Patients are at risk for developing pancreatic cysts and tumors. Other tumors include kidney cancers, pheochromocytoma, eye and central nervous system tumors. These tumors occur at a higher frequency rate than normal population.

Von Hippel Lindau

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Naris Nilubol

Only 319/340 records are available in the database program for this outcome measure. No records are available for the remaining 21 participants.

Number of Patients With Pancreatic Lesions Defined by Simple Cysts, Microcystic Adenomas, Neuroendocrine Tumors & Other Solid Lesions of the Pancreas Who Had Significant Growth in Lesions or Symptoms Related to the Lesions Requiring Surgical Intervention

exon 1 and 2 mutation

exon 3 mutation

The exon mutation information only is available in 63 patients. This protocol did not repeat the gene testing in any of the patients.

Percentage of Participants With Exon 3 Mutation Compared to Participants With Exon 1 or 2 Von Hippel Lindau (VHL) Mutations Who Required an Intervention

Number of Participants From Which We Obtained Tissue From Pancreatic Lesions and Normal Tissue for Genetic Analysis

Von Hippel-Lindau disease (VHL) is an inherited cancer syndrome. Patients are at risk for developing pancreatic cysts and tumors. These tumors are Von Hippel-Lindau disease (VHL) is an inherited cancer syndrome. Patients are at risk for developing pancreatic cysts and tumors. Other tumors include kidney cancers, pheochromocytoma, eye and central nervous system tumors. These tumors occur at a higher frequency rate than normal population.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Magnetic Resonance (MR) Imaging With Hyperpolarized 13C-Pyruvate +/- 13C,15N-Urea in Patients With Prostate Cancer	NCT06391034	Prostate Cancer	hyperpolarized ... Non-investigati... Radiotherapy (R... Multi-parametri... Non-interventio... Prostate Biopsy	18 Years -	University of California, San Francisco
Natural History and Management of Pancreatic Lesions in Von Hippel-Lindau Disease	NCT00062166	Von Hippel-Lind...		12 Years - 80 Years	National Institutes of Health Clinical Center (CC)
Magnetic Resonance (MR) Imaging With Hyperpolarized 13C-Pyruvate +/- 13C,15N-Urea in Patients With Prostate Cancer	NCT06391034	Prostate Cancer	hyperpolarized ... Non-investigati... Radiotherapy (R... Multi-parametri... Non-interventio... Prostate Biopsy	18 Years -	University of California, San Francisco
Magnetic Resonance (MR) Imaging With Hyperpolarized 13C-Pyruvate +/- 13C,15N-Urea in Patients With Prostate Cancer	NCT06391034	Prostate Cancer	hyperpolarized ... Non-investigati... Radiotherapy (R... Multi-parametri... Non-interventio... Prostate Biopsy	18 Years -	University of California, San Francisco
Magnetic Resonance (MR) Imaging With Hyperpolarized 13C-Pyruvate +/- 13C,15N-Urea in Patients With Prostate Cancer	NCT06391034	Prostate Cancer	hyperpolarized ... Non-investigati... Radiotherapy (R... Multi-parametri... Non-interventio... Prostate Biopsy	18 Years -	University of California, San Francisco

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