A Study of CFI-400945 Fumarate in Patients With Advanced Cancer

NCT01954316 | Completed Phase 1 DMC

• 1 other identifier: CFI-400945-CL-001
• Study Type: interventional
• Target: 46
• Locations: 2 countries
• Sites: 2

Brief Summary

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.

Conditions

Advanced Cancer

Keywords

advanced cancer; CFI-400945 fumarate; polo-like kinase 4; PLK4; tablet; dose escalation; genetic testing

Outcome Measures

Primary Outcomes (1)

• 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

  From first dose of study drug until the date of unacceptable toxicity, throughout the study completion, up to 2 years

Secondary Outcomes (8)

• Pharmacokinetic profile of CFI-400945 fumarate (please see description below) over a range of doses and schedules

  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

  through study completion, up to 2 years

• Number of side effects occurring and severity

  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

  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

  At any time from when the patient reaches 3 months on trial or more at the time of progression, up to two years

Study Arms (3)

CFI-400945 fumarate Schedule A

EXPERIMENTAL

CFI-400945 fumarate tablets daily dosing expansion at 64mg

Drug: CFI-400945

CFI-400945 fumarate Schedule B

EXPERIMENTAL

CFI-400945 fumarate tablets intermittent dosing schedule, 2 days on/5 days off. Escalation at following levels: 96mg, 128mg

Drug: CFI-400945

CFI-400945 fumarate Schedule C

EXPERIMENTAL

CFI-400945 fumarate tablets intermittent dosing schedule, 1 day on/6 days off. Escalation will start at MTD of Schedule B

Drug: CFI-400945

Interventions

CFI-400945 DRUG

Polo-like kinase 4 (PLK4) inhibitor

CFI-400945 fumarate Schedule A; CFI-400945 fumarate Schedule B; CFI-400945 fumarate Schedule C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have histologic or cytological proof of advanced cancer that has progressed and for which there is no further standard anticancer therapy available in the opinion of the investigator.
• Patients must have measurable disease as per RECIST v1.1
• Are 18 years of age or older.
• Have clinically acceptable laboratory screening results within certain limits
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Able to swallow oral medications.
• Have a life expectancy greater than 3 months.
• Women and men of child producing potential must agree to use highly effective means of contraception during study participation, and for at least 30 days after the last administration of study medication.
• Negative serum pregnancy test with 72 hours prior to start of study drug
• Have the ability to understand the requirements of the study, provide written informed consent which includes authorization for release of protected health information, abide by the study restrictions, and agree to return for the required assessments.

You may not qualify if:

• Women who are pregnant or nursing.
• Have received radiotherapy, chemotherapy, biological therapy or investigational treatment less than four weeks (six weeks for nitrosourea or mitomycin C) prior to first dose of study medication or have not recovered from all acute toxicities from prior treatments.
• Patients who have received growth factors within 14 days prior to initiation of dosing of CFI-400945 fumarate.
• Have active, acute, or chronic clinically significant infections.
• Have uncontrolled severe hypertension
• Have clinical symptomatic congestive heart failure defined at \>= Class II of the New York Heart Association functional classification system or LVEF \< 50% at baseline.
• Have active angina pectoris or recent myocardial infarction (within 6 months).
• Have chronic atrial fibrillation or QTc of greater than 470 msec, as calculated by Bazett's correction formula.
• Have had major surgery within 21 days of starting therapy. Placement of a venous access device within 21 days of starting therapy is allowed.
• Have additional uncontrolled serious medical or psychiatric illness.
• Have any medical condition that could impair the administration of oral agents including significant bowel resection, inflammatory bowel disease or uncontrolled nausea or vomiting.
• Known central nervous system metastasis. Patients with history of central nervous system metastases are eligible if they are clinically or radiographically stable for at least 3 months and not taking steroids or anticonvulsants.
• Patients being treated with full dose warfarin are excluded. Patients with history of deep vein thrombosis or pulmonary embolus who are being treated with therapeutic doses of low molecular weight heparin or prophylactic dose anticoagulants may be enrolled.
• Patients being treated with certain drugs not acceptable while receiving CFI-400945 fumarate.

Sponsors & Collaborators

• University Health Network, Toronto: lead
• The Princess Margaret Cancer Foundation: collaborator
• California Institute for Regenerative Medicine (CIRM): collaborator

Study Sites (2)

UCLA Medical Center

Santa Monica, California, 90404, United States

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Related Publications (1)

• Veitch ZW, Cescon DW, Denny T, Yonemoto LM, Fletcher G, Brokx R, Sampson P, Li SW, Pugh TJ, Bruce J, Bray MR, Slamon DJ, Mak TW, Wainberg ZA, Bedard PL. Safety and tolerability of CFI-400945, a first-in-class, selective PLK4 inhibitor in advanced solid tumours: a phase 1 dose-escalation trial. Br J Cancer. 2019 Aug;121(4):318-324. doi: 10.1038/s41416-019-0517-3. Epub 2019 Jul 15.

  PMID: 31303643 DERIVED

Related Links

• Jacqueline Mason et al. Functional characterization of CFI-400945, a Polo-like kinase 4 inhibitor, as a potential anticancer agent. Cancer Cell. 2014 Aug 11;26(2):163-76.

MeSH Terms

Interventions

2-(3-(4-((2,6-dimethylmorpholino)methyl)styryl)-1H-indazol-6-yl)-5'-methoxyspiro(cyclopropane-1,3'-indolin)-2'-one

Study Officials

• Philippe Bedard, M.D.

  Princess Margaret Cancer Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2013
• First Posted: October 1, 2013
• Study Start: March 1, 2014
• Primary Completion: July 1, 2021
• Study Completion: July 22, 2021
• Last Updated: January 17, 2024

Record last verified: 2024-01

Locations

US (1); CA (1)