Clinical trial NCT01240551: F-18 Sodium Fluoride in Prostate Cancer
Official title: A Pilot Study of F-18 Sodium Fluoride PET/CT for Metastatic Burden Qualification in Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Neoplasm
Keywords: Imaging
Bone Metastasis
Bone Scan
Radiopharmaceutical
Pet Scan
Prostate Cancer
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2010-11-15
Enrollment: 60
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: Background:

- Sodium fluoride (NaF) is a common compound that is found in various foods and can be used to increase bone strength. When this compound is added to a small dose of radiation (F-18), it collects in the bones, with higher amounts in areas where the bone is rapidly changing, such as the site of a healing fracture or a tumor. By giving F-18 NaF before a combined positron emission tomography/ computed tomography (PET/CT) scan, researchers hope to be able to better measure the changes in the bone that may indicate that a certain type of cancer (such as prostate cancer) has spread to the bones.

Objectives:

* To evaluate the effectiveness of F-18 NaF in imaging studies to measure bone tumors and their change over time and compare with clinical course, in individuals with prostate cancer.
* To determine the smallest amount of change in the bone tumors that F-18 NaF can accurately measure.

Eligibility:

- Men at least 18 years of age who have been diagnosed with prostate cancer and have had imaging studies to determine whether the cancer has spread to their bones. Both patients with and without known bone involvement will be enrolled.

Design:

* Participants will be screened with a physical examination, medical history, and imaging studies, and will provide baseline blood samples to evaluate kidney function.
* For the study, participants will have two F-18 NaF PET/CT scans on separate days for baseline. These repeat scans will be used to determine the amount of change that is due to the imaging process alone (i.e. not due to the disease getting better or worse. Participants will receive a dose of F-18 NaF intravenously, and will have PET/CT scanning over the body (mid ear to upper thighs) over 1 hour, the body followed by a complete whole-body PET/CT scan at approximately 2 hours after F-18 NaF injection. Participants will be watched closely for side effects from the F-18 NaF until the scans are done, and will be asked to drink plenty of water to void the F-18 NaF from the body after the scans.
* As a followup study, participants will have two more F-18 NaF PET/CT scans, one 4 to 8 months after the first scans and then one 10 to 14 months after the first scans. Participants will provide additional blood samples before the followup scans.

Detailed description: Background:

* Evaluating response to therapy in prostate cancer is limited by the inability to quantify bony metastatic disease
* F-18 sodium fluoride (NaF) is a PET radiopharmaceutical which localizes in regions of bony turnover, and was the 1st bone scan agents (prior to Tc-99m MDP (methylene diphosphonate) availability)
* Today s high sensitivity PET cameras can image the distribution of F-18 NaF as a whole body volume and permit quantification of uptake over time. The addition of co-registered CT increases the diagnostic accuracy for detection of metastatic disease

Primary Objective:

-To evaluate the feasibility of using NaF PET/CT to quantitatively measure the extent of bony metastatic disease in patients with prostate cancer in patients

* To determine the intra-patient reproducibility of F-18 NaF PET/CT
* To explore the relationship between the biodistribution changes in F-18 NaF PET/CT parameters and the clinical response

Eligibility:

* Participant must have pathology proven adenocarcinoma of the prostate.
* Participant must have

  * A history of PSA \> 10ng/mL or a history of PSA doubling time of less than or equal to 6 months, and no known bone metastatic involvement on standard of care imaging (Tc-99m MDP bone scan, CT etc).

OR

--Any PSA (prostate specific antigen) level and known bone metastatic disease on standard of care imaging (Tc-99m MDP bone scan, CT etc.)

* Participant must be 18 years or older and have ECOG (Eastern Cooperative Oncology Group) Performance grade of 0 to 2
* Ability to provide informed consent. All subjects must sign a document of informed consent indicating their understanding of the investigational nature and risks of the study before any protocol related studies are performed.

Design:

This is a pilot, 2-arm, open label study of patients with prostate cancer. One arm will accrue patients with known bone metastases and the second will accrue patient at risk of developing bone metastases (30 patients per group; total enrollment 60 patients). As it is possible that there will be different rates of bone lesion detection dependent on hormone responsiveness of the tumors, further stratification (castrate sensitive vs. castrate resistant tumor) may be performed to evaluate for predominant trends. All participants will undergo a static F-18 NaF imaging session at baseline, at 4-8 months, and at 10-14 months following enrollment (3 sessions over 1-year). Half of the participants (15 in each group) will undergo two baseline F-18 NaF PET/CT imaging sessions (within 14-days of each other) in order to evaluate the reproducibility of F-18 NaF PET imaging for a total of 4 sessions over a 1-year period. The change in bone uptake of F-18 NaF will be measured, reproducibility determined, and preliminary comparisons with clinical response will be made.

Eligibility criteria: * INCLUSION CRITERIA:

Participants must have a clinical course consistent with prostate cancer and have available documentation of prostate adenocarcinoma from either the National Cancer Institute (NCI) or from an outside pathology laboratory.

Participant must have:

- A history of PSA of \> 10ng/mL or a history of PSA doubling time of less than or equal to 6 months, and no known bone metastatic involvement on standard of care imaging (Tc-99m MDP bone scan, CT etc)

OR

- Any PSA level and known bone metastatic disease on standard of care imaging (Tc-99m MDP bone scan, CT etc).

Ability to provide informed consent. All subjects must sign a document of informed consent indicating their understanding of the investigational nature and risks of the study before any protocol related studies are performed.

EXCLUSION CRITERIA:

Participants with severe claustrophobia unresponsive to oral anxiolytics.

Subjects weighing greater than 350 lbs (weight limit for scanner table), or unable to fit within the imaging gantry.

Subjects with any medical condition or other circumstances that, in the opinion of the Investigator, would significantly decrease obtaining reliable data, achieving study objectives or completing the study.

Primary outcomes:
measure: Number of Participants With Present or Not Present Bone Metastasis
timeFrame: Single imaging sessions will be acquired at baseline, between 4-6 months and between 10-12 months on emolument.
Secondary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: date treatment consent signed to date off study, approximately 52.5 months
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center, 9000 Rockville Pike
state: Maryland
Study officials:
affiliation: National Cancer Institute (NCI)
name: Karen A Kurdziel, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Scher HI, Halabi S, Tannock I, Morris M, Sternberg CN, Carducci MA, Eisenberger MA, Higano C, Bubley GJ, Dreicer R, Petrylak D, Kantoff P, Basch E, Kelly WK, Figg WD, Small EJ, Beer TM, Wilding G, Martin A, Hussain M; Prostate Cancer Clinical Trials Working Group. Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol. 2008 Mar 1;26(7):1148-59. doi: 10.1200/JCO.2007.12.4487.
citation: Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, Oudard S, Theodore C, James ND, Turesson I, Rosenthal MA, Eisenberger MA; TAX 327 Investigators. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004 Oct 7;351(15):1502-12. doi: 10.1056/NEJMoa040720.
citation: Grant FD, Fahey FH, Packard AB, Davis RT, Alavi A, Treves ST. Skeletal PET with 18F-fluoride: applying new technology to an old tracer. J Nucl Med. 2008 Jan;49(1):68-78. doi: 10.2967/jnumed.106.037200. Epub 2007 Dec 12.
citation: Kurdziel KA, Shih JH, Apolo AB, Lindenberg L, Mena E, McKinney YY, Adler SS, Turkbey B, Dahut W, Gulley JL, Madan RA, Landgren O, Choyke PL. The kinetics and reproducibility of 18F-sodium fluoride for oncology using current PET camera technology. J Nucl Med. 2012 Aug;53(8):1175-84. doi: 10.2967/jnumed.111.100883. Epub 2012 Jun 22.