CFI-400945 in Patients With Advanced/Metastatic Breast Cancer

NCT03624543 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: I237
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 6

Brief Summary

The standard or usual treatment for this disease is to undergo chemotherapy to slow the spread of the disease and relieve some symptoms of cancer. Patients will have already had at least one chemotherapy treatment for their disease at this stage.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response defined by RECIST 1.1

  2 years

Secondary Outcomes (4)

• Disease Control Rate (DCR) defined by RECIST 1.1

  2 years

• Number and severity of adverse events

  2 years

• Molecular analyses of CFI-400945 on tumour cells through paired tumour biopsies using next generation DNA sequencing

  2 years

• Molecular analyses of CFI-400945 on tumour cells through paired biopsies using immunohistochemistry

  2 years

Study Arms (3)

Cohort 1: TNBC

EXPERIMENTAL

N=9 to 24 patients

Drug: CFI-400945

Cohort 2: PTEN-null, ER+ and/or PR+, HER2-

EXPERIMENTAL

N=9 to 24 patients

Drug: CFI-400945

Cohort 3: Not PTEN-null, ER+ and/or PR+, HER2-

EXPERIMENTAL

N=9 to 24 patients

Drug: CFI-400945

Interventions

CFI-400945 DRUG

32mg; 28 day cycles; Cycle 1: Days 1-7 then 15-21 Cycle 2 onward: Daily

Cohort 1: TNBC; Cohort 2: PTEN-null, ER+ and/or PR+, HER2-; Cohort 3: Not PTEN-null, ER+ and/or PR+, HER2-

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically and/or cytologically confirmed diagnosis of breast cancer, that is advanced/metastatic/recurrent or unresectable, for which no curative therapy exists, either:
• Negative for ER, PR and HER2 by ASCO/CAP criteria (COHORT 1) OR
• Positive for ER and or PR and negative for HER2 AND
• loss or mutation of PTEN, as assessed by IHC assay (COHORT 2) OR
• No loss or mutation of PTEN, as assessed by IHC assay (COHORT 3)
• For the patients entered on the PK/safety component only, results of the PTEN status may be documented after enrollment
• Only female patients will be enrolled.
• All patients must have a formalin fixed paraffin embedded tissue block (from primary or metastatic tumour) available and must have provided informed consent for the release of the block. Biopsies are optional but strongly encouraged for patients with accessible disease suitable for biopsy. The timing of tumour biopsies for patients who provide informed consent and willing is prior to treatment (after enrollment), and again between cycle 2 day 15- day 22. An additional biopsy at the time of progression in patients with clinical benefit is also encouraged. Lesions planned for biopsy may not be the only target lesion.
• Presence of clinically and/or radiologically documented disease. All radiology studies must be performed within 21 days prior to enrollment (within 28 days if negative).
• All patients must have measurable disease as defined by RECIST 1.1. The criteria for defining measurable disease are as follows: Chest x-ray ≥ 20 mm CT scan (with slice thickness of 5 mm) ≥ 10 mm --\> longest diameter Physical exam (using calipers) ≥ 10 mm Lymph nodes by CT scan ≥ 15 mm --\> measured in short axis
• Patients must be ≥ 18 years of age.
• Patients must have an ECOG performance status of 0 or 1.
• Patients must have a life expectancy of 3 months or longer.
• Laboratory Requirements (must be done within 7 days prior to enrollment) Absolute neutrophils ≥ 1.5 x 10\^9/L Platelets ≥ 100 x 10\^9/L Bilirubin ≤ 1.5 x ULN (upper limit of normal) AST and ALT ≤ 2.5 x ULN; ≤ 4.0 x ULN if patient has liver metastases Serum creatinine ≤ 1.5 x ULN or Creatinine clearance ≥ 50 mL/min
• Patients must be able to swallow oral medications and have no known gastrointestinal disorders that may interfere with absorption (such as malabsorption).

You may not qualify if:

• Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for \> 2 years and which do not require ongoing treatment.
• Patients with active or uncontrolled infections or with serious illnesses or medical conditions which would not permit the patient to be managed according to the protocol.
• Patients are not eligible if they have a known hypersensitivity to the study drug(s) or their components.
• Patients with HER2 positive breast cancer (based on the most recent assessment).
• Patients with significant cardiac (including uncontrolled hypertension) or pulmonary disease, or active CNS disease or infection. Patients should have a LVEF ≥ 50%.
• Patients may not receive concurrent treatment with other anti-cancer therapy (other than bone-targeted therapy, if already taking and stable) or investigational agents while on protocol therapy.
• Patients who have received growth factors within 28 days prior to initiation of dosing of CFI-400945 or who will require treatment with growth factors throughout the duration of the trial.
• Pregnant or breastfeeding women.
• Patients being treated with drugs listed in Appendix V Table 1 are excluded. Patients being treated with drugs listed in Appendix V Table 2 may be enrolled, but should be monitored carefully for toxicities resulting from potential interactions between CFI-400945m and these drugs. In addition, patients must avoid consumption of the fruit or juice of Seville oranges (e.g. marmalade), grapefruit, pomelos and star fruit from 7 days before the first dose of study drug and during the entire study due to potential CYP3A4 interaction with the study drug. Regular orange juice is allowed.
• Patients with history of central nervous system metastases or spinal cord compression unless they have received definitive treatment, are clinically stable and do not require corticosteroids.
• Patients with any medical condition that would impair the administration of oral agents including significant bowel resection, inflammatory bowel disease or uncontrolled nausea or vomiting.
• Patients being treated with full dose warfarin. Patients with history of deep vein thrombosis or pulmonary embolus who are being treated with therapeutic doses of low molecular weight heparin, direct factor Xa inhibitors or prophylactic dose anticoagulants may be enrolled

Sponsors & Collaborators

• Canadian Cancer Trials Group: lead
• Stand Up To Cancer Canada-Canadian Cancer Society Breast Cancer Dream Team: collaborator

Study Sites (6)

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

London Regional Cancer Program

London, Ontario, N6A 5W9, Canada

Location

Ottawa Hospital Research Institute

Ottawa, Ontario, K1H 8L6, Canada

Location

Odette Cancer Centre

Toronto, Ontario, M4N 3M5, Canada

Location

University Health Network

Toronto, Ontario, M5G 2M9, Canada

Location

Allan Blair Cancer Centre

Regina, Saskatchewan, S4T 7T1, Canada

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

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

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• David Cescon

  Princess Margaret Cancer Centre, Toronto, ON

  STUDY CHAIR

• Rossanna Pezo

  Sunnybrook Health Sciences Centre, Toronto, ON

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 1, 2018
• First Posted: August 10, 2018
• Study Start: February 14, 2019
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 30, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (6)