A Phase 1 Ascending-dose Study to Assess the Safety and Tolerability and Imaging Potential of Hyperpolarized Pyruvate (13C) Injection in Subjects With Prostate Cancer
18 Years
N/A
Male
Prostate Cancer
Trial Information
A Phase 1 Ascending-dose Study to Assess the Safety and Tolerability and Imaging Potential of Hyperpolarized Pyruvate (13C) Injection in Subjects With Prostate Cancer
This is a phase 1 clinical study of an investigational medicinal product (IMP),
hyperpolarized Pyruvate (13C) Injection. The study includes the acquisition of magnetic
resonance (MR) data and will be performed in men with prostate cancer and intact prostates.
A standard dose-escalation design will be used; initially, 6 subjects will receive IMP at
each dose level. As data on both the dynamics of arrival of the IMP and potential imaging
efficacy are needed at each dose level, requiring the use of separate MR acquisition
sequences, a modified 3+3 design will be applied in each dose cohort. The first 3 subjects
will undergo dynamic 13C imaging to define the kinetics of delivery and metabolism of IMP,
and the second 3 subjects will undergo 13C MR spectroscopic imaging (MRSI) to obtain
3-dimensional (3-D) spatial information about metabolism of IMP in regions of the prostate
with and without cancer involvement.
After the apparent maximum tolerated dose (MTD) has been established, there will be an
expansion of the 3-D imaging cohort to 6 subjects (9 subjects in total at this dose level)
to obtain additional information regarding safety at the MTD. If >2 subjects from this
cohort of 9 subjects experience a dose-limiting toxicity (DLT), the next lower dose will be
defined as the MTD. At the dose level with the highest contrast to noise ratio (dose level
less than or equal to the MTD) there will be an expansion of the imaging cohort to include
another 15 subjects for a total of 18 subjects who undergo 13C 3-D scanning at this dose, to
obtain exploratory information concerning the time course and SNR (signal to noise ratio) of
the presence of hyperpolarized [1 13C] pyruvate and its metabolites in regions of cancer and
benign prostate tissues. The information provided by these data will be used to develop the
MR imaging protocol for future clinical trials that will seek to address the sensitivity and
specificity of the technology.
Inclusion Criteria
INCLUSION CRITERIA:
1. The subject has biopsy-proven prostate cancer and is either undergoing active
surveillance ("watchful waiting") or pre primary local treatment for prostate cancer
(i.e., prior to either radiation therapy or radical prostatectomy).
2. The subject is able and willing to comply with study procedures and provide signed
and dated informed consent.
3. The subject has concordant MRI/1H MRSI findings from a prior MR staging exam
performed within 8 weeks of the 13C MRSI exam performed in this study with IMP, or is
willing to undergo MRI/1H MRSI in connection with the study exam.
4. Negative test for hepatitis B and hepatitis C.
5. Eastern Cooperative Oncology Group Performance Status of 0 or 1.
6. Laboratory criteria for protocol entry:
- Absolute neutrophil count (ANC) >/= 1500 cells/microLiters
- Hemoglobin >/= 9.0 gm/dL
- Platelets >/= 100,000 cells/microLiters
- Estimated creatinine clearance >/= 60 mL/min (by the Cockcroft Gault equation)
- Bilirubin within normal range
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) within
normal range
7. Willing to use contraception during and for 1 month after completion of the study.
EXCLUSION CRITERIA:
1. The subject has received, or is scheduled to receive, another IMP from 1 month before
to 1 month after inclusion in this study.
2. Current or prior androgen deprivation therapy; previous use of a 5-alpha reductase
inhibitor is allowed, provided it was discontinued at least 1 month prior to study
entry.
3. Poorly controlled hypertension, with blood pressure at study entry >150/90.
4. Contraindication for or inability to tolerate MRI examination.
5. Prostate biopsy within 12 weeks prior to study entry.
6. BMI of less than 18.5 or greater than 32. At the 0.43 ml/kg dose, subject body
weight should be less than or equal to 100 kg owing to limitations in the amount of
IMP available.
7. Congestive heart failure or New York Heart Association (NYHA) status >2.
8. A past or present medical history of clinically significant electrocardiogram (EKG)
abnormalities, including QT prolongation, a family history of prolonged QT interval
syndrome, or myocardial infarction (MI) less than 1 year ago with ensuing unstable
EKG.
9. Ongoing acute or chronic pulmonary bronchospastic disease, including a history of
chronic obstructive pulmonary disease or asthma, with an exacerbation within the past
year.
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic
Outcome Measure:
Number of Participants with Adverse Events as a Measure of Safety and Tolerability.
Outcome Description:
Assessment of the occurrence of clinically significant changes in safety variables from baseline. Safety endpoints include monitoring for the occurrence of treatment-emergent AEs. Monitoring will occur to evaluate for dose-limiting toxicity. Dose-Limiting Toxicity (DLT) is defined as any toxicity greater than or equal to grade 2, 3 or 4, attributable to the imaging agent and occurring within 7 days after administration. The maximum tolerated dose will be the dose level at which <33% DLT occurs.
Outcome Time Frame:
7 days
Safety Issue:
Yes
Principal Investigator
Charles Ryan, M.D.
Investigator Role:
Principal Investigator
Investigator Affiliation:
University of California, San Francisco
Authority:
United States: Food and Drug Administration
Study ID:
085517
NCT ID:
NCT01229618
Start Date:
October 2010
Completion Date:
December 2015
Related Keywords:
- Prostate Cancer
- Prostate Cancer
- Prostatic Neoplasms
Name | Location |
|---|---|
| University of California San Francisco | San Francisco, California 941104206 |
