This is a phase 1 study to test different doses of a new investigational drug called CFI-400945 to see which dose is safer in people. This study will also look at the safety of CFI-400945 and to study its effects on patients with advanced cancers. This drug has been tested in animals but not yet in people. CFI-400945 is an oral (taken by mouth) drug that works by blocking polo-like kinase 4 (PLK4) from working. PLK4 is a protein that is important in regulating cell growth and division and cell death. Many tumors are shown to make too much PLK4. When there is too much PLK4 produced, it is believed to lead to uncontrolled cancer cell growth and division. Therefore, by blocking this protein from working, it is believed to stop tumors growing or shrink them.
All participants will receive CFI-400945. At the beginning of the study, participants are given a low dose of CFI-400945 and are watched very closely to see what side effects they have and to make sure the side effects are not severe. If the side effects are not severe, then more participants are asked to join the study and are given a higher dose of study drug. Participants joining the study later on will get higher doses of study drug than participants who join earlier. This will continue until the highest dose of study drug that can be taken without severe side effects is found (called maximum tolerated dose). Doses higher than that will not be given. After the best dose of study drug is found, additional participants will be asked to join the study and will be given the study drug at the maximum tolerated dose to further test the safety and the drug at that dose.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
46
Polo-like kinase 4 (PLK4) inhibitor
UCLA Medical Center
Santa Monica, California, United States
Princess Margaret Cancer Centre
Toronto, Ontario, Canada
Highest dose level that does not lead to unacceptable toxicity in two or more patients in a dosing group over a range of doses and schedules
Though evaluation of AEs and DLTS of all patients who have received study drug
Time frame: From first dose of study drug until the date of unacceptable toxicity, throughout the study completion, up to 2 years
Pharmacokinetic profile of CFI-400945 fumarate (please see description below) over a range of doses and schedules
* Area under the plasma concentration-time curve (AUC) * Elimination half-life (T½) * Maximum plasma concentration (Cmax) * Minimum plasma concentration (Cmin) * Time when Cmax occurs (Tmax) * Average plasma concentration at steady state (Cavg)
Time frame: Day 1 and Day 28 of Cycle 1 prior to first dose and at 0.5, 1, 2 (± 5 minutes), 4, 6, 8, 10-12 (± 15 minutes), and 24 hours (± 60 minutes) following dosing. Day 1 of Cycle 2 and future cycles, prior to dosing.
Number of patients with evidence of benefit over a range of doses and schedules
response to treatment and/or clinical benefit or tumor marker improvement
Time frame: through study completion, up to 2 years
Number of side effects occurring and severity
by frequency and severity of treatment emergent adverse events in cancer patients
Time frame: through study completion, up to 2 years
Evaluate the genomic alterations and other molecular features which are associated with response and/or clinical benefit with CFI-400945-CL fumarate treatment
Through optional tumor biopsies; Gene or protein expression levels
Time frame: At any time from when the patient reaches 3 months on trial or more at the time of progression
to evaluate pharmacodynamics effects relative to CFI-400945 fumarate at MTD
Through baseline biopsy comparisons with optional tumor biopsy at the time of progression
Time frame: At any time from when the patient reaches 3 months on trial or more at the time of progression, up to two years
Determine evidence of benefit in cancer patients when CFI-400945 fumarate is administered orally at the MTD (expansion)
Evaluating tumor response(if appropriate) and/or clinical benefit or tumor marker improvement
Time frame: At any time from when the patient reaches 3 months on trial or more at the time of progression, up to two years
To evaluate possible mechanisms of resistance to CFI-400945 fumarate at MTD
Through optional baseline biopsy comparisons with optional tumor biopsy at the time of progression
Time frame: At any time from when the patient reaches 3 months on trial or more at the time of progression, up to two years
Determine recommended Phase 2 dose for CFI-400945 fumarate
Time frame: Based on safety profile evaluated throughout the DLT period, which is Cycle 1 (each cycle being 28 days) of treatment, and through study completion up to two years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.