Prostate Cancer, Prostate Cancer Metastatic, Prostatic Neoplasm
Conditions
Brief summary
18F-DCFPyL is an agent that binds to prostate specific membrane antigen (PSMA). Due to high levels of PSMA in prostate cancer, treatments targeting PSMA have been developed to deliver therapy to these specific target cells. Unfortunately when this treatment is delivered there is radiotracer uptake in the salivary glands and kidneys, not related to cancer, which causes dry mouth and causes patients to stop treatment. It is proposed that having tomato juice containing monosodium glutamate (MSG) may reduce radiotracer uptake in the salivary glands and kidneys and reduce damage to these tissues.
Detailed description
This is a prospective single cohort study to evaluate the utility of MSG in reducing salivary gland radiotracer uptake, in patients who undergo an 18F-DCFPyL Positron Emission tomography / Computer Tomography (PET/CT) scan. 18F-DCFPyL PET/CT scans Each participant will receive 2 18F-DCFPyL PET/CT scans at the BC Cancer - Vancouver Centre, as part of this research sub-study. Each participant will receive tomato juice before each appointment. One visit they will have tomato juice containing MSG and the other will be a placebo (standard tomato juice). Each study participant will receive a bolus intravenous dose of 18F-DCFPyL. The participant will rest in a comfortable chair for 120 minutes and will then be taken to the PET/CT scanner for images. 24 hour follow-up All participants will be requested to either return to the functional imaging department approximately 24 hours (acceptable range 16-28 hours) after the injection of 18F-DCFPyL and tomato juice consumption or agree to be contacted by phone. The participants will be asked if they experienced any undesirable effects following the administration of 18F-DCFPyL and tomato juice, or in the intervening 24 hours. The local site attending nuclear medicine physician will then make an assessment as to whether these effects are likely related to 18F-DCFPyL and/or tomato juice administration. The study is expected to take approximately 1 year for accrual.
Interventions
DIAGNOSTIC_TEST18F-DCFPyL PET/CT scan
Participants will have their weight recorded and baseline vital signs (blood pressure, heart rate, and oxygen saturation level) measured prior to the tomato juice ingestion, immediately prior to 18F-DCFPyL injection and 5 to 15 minutes after injection. The participant will receive a bolus intravenous dose of 18F-DCFPyL. After 60 min, the vital signs will be recorded and again two hours after 18F-DCFPyL. Immediately before scanning, the participants will be taken to a designated washroom and asked to void. The PET/CT image acquisition time will be approximately 30 minutes.
OTHERPlacebo drink
Participants will consume 300mL of tomato juice 30 minutes prior to 18F-DCFPyL injection.
OTHERMSG drink
Participants will consume 300mL of tomato juice with MSG 30 minutes prior to 18F-DCFPyL injection.
Sponsors
British Columbia Cancer Agency
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
DIAGNOSTIC
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Masking description
For randomization, a computer generated random list will determine the order of the scans (MSG first, placebo first). Sealed envelopes will be prepared. A study coordinator or technologist not involved in measuring vital signs or collecting adverse events will prepare the tomato juice solution based on the randomization envelope. The rest of the team will not be informed of which tomato juice is used (placebo or MSG) but this information will be recorded and will be immediately accessible should a participant experience a severe adverse event.
Intervention model description
This is a prospective double blind intra-participant comparison of \[18F\]-DCFPyL PET/CT scans performed after orally administered MSG or placebo. The participants will receive oral administration of MSG or placebo, in two different examination sessions, 30 minutes before \[18F\]-DCFPyL injection.
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Known prostate cancer with biochemical recurrence after initial curative therapy with radical prostatectomy, presenting with a prostate specific antigen (PSA) greater than 0.4 ng/mL. * Subjects with findings on other examinations (such as plain x-ray, CT, MRI or bone scintigraphy and others) that are suspicious for metastatic disease but not conclusively diagnostic of metastatic disease, within 3 months of PET scan. * Known prostate cancer with biochemical recurrence after initial curative therapy with radiation therapy (including brachytherapy), with a PSA level \>2 ng/mL above the nadir after radiation therapy. * Castration resistant prostate cancer with a minimum PSA of 2.0 ng/mL with 2 consecutive rises above the nadir and castrate levels of testosterone (\<1.7 nmol/L). Treatment does not need to be discontinued before the 18F-DCFPyL scan. * Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less.
Exclusion criteria
* Medically unstable (eg. acute illness, unstable vital signs) * Unable to lie supine for the duration of imaging * Unable to provide written consent * Exceeds safe weight limit of the PET/CT bed (204.5 kg) or unable to fit through the PET/CT bore (diameter 70 cm) * Severe uncontrolled hypertension (systolic blood pressure above 140 mm Hg and diastolic blood pressure above 90 mm Hg, or systolic blood pressure above 180 mm Hg, or diastolic blood pressure above 110 mg Hg). Patients with controlled hypertension under medication are eligible * History of severe asthma that has led to hospitalizations or emergency room visits * History of intolerance to MSG * History of severe headaches or migraines triggered by food or MSG * Participants on a sodium/salt restricted diet due to other medical conditions * No new treatment has started between the first and second 18F-DCFPyL PET/CT
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Salivary Gland Maximal Standardized Uptake Values Corrected for Lean Body Mass (SULmax) for 18F-DCFPyL | scan with MSG and 3-7 days later, scan with Placebo (or vice versa) | Comparison of MSG and placebo 18F-DCFPyL salivary gland (submandibular) accumulation measured by the maximal standardized uptake values corrected for lean body mass (SULmax). For determination of salivary gland uptake, regions of interest will be drawn around the salivary glands, using a standardized contouring method, to measure the SULmax. The average SULmax in the organs will be used for this analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Renal Maximal Standardized Uptake Values Corrected for Lean Body Mass (SULmax) for 18F-DCFPyL | scan with MSG and 3-7 days later, scan with Placebo (or vice versa) | Comparison of MSG and placebo 18F-DCFPyL renal accumulation measured by the maximal standardized uptake values corrected for lean body mass (SULmax). For determination of renal uptake, regions of interest will be drawn around the kidneys, using a standardized contouring method, to measure the SULmax. The average SULmax in the organs will be used for this analysis. |
| Tumour Maximal Standardized Uptake Values Corrected for Lean Body Mass (SULmax) for 18F-DCFPyL | scan with MSG and 3-7 days later, scan with Placebo (or vice versa) | Comparison of MSG and placebo 18F-DCFPyL tumour accumulation measured by the maximal standardized uptake values corrected for lean body mass (SULmax). For determination of tumour uptake, all malignant lesions, the SULmax were measured using the PET Edge tool running on MIM. All regions of interest were created in one dataset by a blinded observer, and then saved and compared to the identical location in the second dataset for matched comparisons of activity. The median SULmax in the malignant lesions will be used for this analysis. |
| Number of Participants With Tomato Juice (Containing Either MSG or Placebo) Related Adverse Events as Assessed by Abnormal Vital Sign Measurement. | 2 hours | Vital signs (blood pressure, heart rate and pulse oximetry) will be measured at two time points (before tomato juice and 2 hours after radiotracer injection). All values that fall outside of the normal parameters will be assessed by a physician and reported as an adverse event. |
Countries
Canada
Participant flow
Recruitment details
Biochemically recurrent prostate cancer patients were screened from a PSMA study wait list, for eligibility between November 1, 2019 and December 1, 2019 at BC Cancer, Vancouver BC. 10 participants were enrolled between November 4th 2019, and December 5th 2019.
Pre-assignment details
10 of 10 participants were randomized.
Participants by arm
| Arm | Count |
|---|---|
| MSG, Then Placebo After a fasting period of 4 hours, participants first received oral administration of 12.7 g of food grade MSG dissolved in 300 mL low sodium tomato juice, prior to receiving the 18F-DCFPyL radio-tracer administration for their PET/CT scan.
Within 1 week, participants returned and after having fasted for 4 hours, then received oral administration of the Placebo (300 mL regular sodium tomato juice) prior to receiving the 18F-DCFPyL radio-tracer administration for their PET/CT scan. | 7 |
| Placebo, Then MSG After a fasting period of 4 hours, participants first received oral administration of the Placebo (300 mL regular sodium tomato juice) prior to receiving the 18F-DCFPyL radio-tracer administration for their PET/CT scan.
Within 1 week, participants returned and after having fasted for 4 hours, then received oral administration of 12.7 g of food grade MSG dissolved in 300 mL low sodium tomato juice, prior to receiving the 18F-DCFPyL radio-tracer administration for their PET/CT scan. | 3 |
| Total | 10 |
Baseline characteristics
| Characteristic | MSG, Then Placebo | Placebo, Then MSG | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 3 Participants | 10 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex/Gender, Customized Male | 7 Participants | 3 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 0 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 |
Outcome results
Primary
Salivary Gland Maximal Standardized Uptake Values Corrected for Lean Body Mass (SULmax) for 18F-DCFPyL
Comparison of MSG and placebo 18F-DCFPyL salivary gland (submandibular) accumulation measured by the maximal standardized uptake values corrected for lean body mass (SULmax). For determination of salivary gland uptake, regions of interest will be drawn around the salivary glands, using a standardized contouring method, to measure the SULmax. The average SULmax in the organs will be used for this analysis.
Time frame: scan with MSG and 3-7 days later, scan with Placebo (or vice versa)
Population: All participants who received at least one dose of each intervention and completed all study visits were included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 18F-DCFPyL PET/CT Scan With MSG Drink | Salivary Gland Maximal Standardized Uptake Values Corrected for Lean Body Mass (SULmax) for 18F-DCFPyL | 9.9 SULmax | Standard Deviation 4.8 |
| 18F-DCFPyL PET/CT Scan With Placebo Drink | Salivary Gland Maximal Standardized Uptake Values Corrected for Lean Body Mass (SULmax) for 18F-DCFPyL | 15.1 SULmax | Standard Deviation 6.2 |
Comparison: Null hypothesis is that there was no difference in uptake of F18-DCFPyL between the MSG and placebo groups.~A sample size of 10 achieves 100% power to detect a mean of paired differences of 5.0 (33%) with an estimated standard deviation of differences of 1.0 and with a significance level (alpha) of 0.05 using a one-sided paired t-test. If the estimated standard deviation of differences is 5.0, a sample size of 10 achieves 90% power to detect a mean difference of 5.0 with an alpha of 0.05.p-value: <0.001Mixed Models Analysis
Secondary
Number of Participants With Tomato Juice (Containing Either MSG or Placebo) Related Adverse Events as Assessed by Abnormal Vital Sign Measurement.
Vital signs (blood pressure, heart rate and pulse oximetry) will be measured at two time points (before tomato juice and 2 hours after radiotracer injection). All values that fall outside of the normal parameters will be assessed by a physician and reported as an adverse event.
Time frame: 2 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 18F-DCFPyL PET/CT Scan With MSG Drink | Number of Participants With Tomato Juice (Containing Either MSG or Placebo) Related Adverse Events as Assessed by Abnormal Vital Sign Measurement. | 0 Participants |
| 18F-DCFPyL PET/CT Scan With Placebo Drink | Number of Participants With Tomato Juice (Containing Either MSG or Placebo) Related Adverse Events as Assessed by Abnormal Vital Sign Measurement. | 0 Participants |
Secondary
Renal Maximal Standardized Uptake Values Corrected for Lean Body Mass (SULmax) for 18F-DCFPyL
Comparison of MSG and placebo 18F-DCFPyL renal accumulation measured by the maximal standardized uptake values corrected for lean body mass (SULmax). For determination of renal uptake, regions of interest will be drawn around the kidneys, using a standardized contouring method, to measure the SULmax. The average SULmax in the organs will be used for this analysis.
Time frame: scan with MSG and 3-7 days later, scan with Placebo (or vice versa)
Population: All participants who received at least one dose of each intervention and completed all study visits were included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 18F-DCFPyL PET/CT Scan With MSG Drink | Renal Maximal Standardized Uptake Values Corrected for Lean Body Mass (SULmax) for 18F-DCFPyL | 27.4 SULmax | Standard Deviation 8 |
| 18F-DCFPyL PET/CT Scan With Placebo Drink | Renal Maximal Standardized Uptake Values Corrected for Lean Body Mass (SULmax) for 18F-DCFPyL | 37.5 SULmax | Standard Deviation 9.6 |
Secondary
Tumour Maximal Standardized Uptake Values Corrected for Lean Body Mass (SULmax) for 18F-DCFPyL
Comparison of MSG and placebo 18F-DCFPyL tumour accumulation measured by the maximal standardized uptake values corrected for lean body mass (SULmax). For determination of tumour uptake, all malignant lesions, the SULmax were measured using the PET Edge tool running on MIM. All regions of interest were created in one dataset by a blinded observer, and then saved and compared to the identical location in the second dataset for matched comparisons of activity. The median SULmax in the malignant lesions will be used for this analysis.
Time frame: scan with MSG and 3-7 days later, scan with Placebo (or vice versa)
Population: All participants who received at least one dose of each intervention and completed all study visits were included in the efficacy analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 18F-DCFPyL PET/CT Scan With MSG Drink | Tumour Maximal Standardized Uptake Values Corrected for Lean Body Mass (SULmax) for 18F-DCFPyL | 2.8 SULmax |
| 18F-DCFPyL PET/CT Scan With Placebo Drink | Tumour Maximal Standardized Uptake Values Corrected for Lean Body Mass (SULmax) for 18F-DCFPyL | 4.4 SULmax |