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.
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic
Number of Participants with Adverse Events as a Measure of Safety and Tolerability.
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.
Charles Ryan, M.D.
University of California, San Francisco
United States: Food and Drug Administration
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