- 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. At least 10 patients per cohort (5 in stage 1 and 5 in stage 2)
must also have accessible disease suitable for biopsy, have provided informed consent
for and be willing to undergo a tumour biopsy prior to treatment (after enrollment),
again between cycle 2 day 15- day 22.
- 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 â‰¥ 20 mm CT scan (with slice
thickness of 5 mm) â‰¥ 10 mm --> longest diameter Physical exam (using calipers) â‰¥ 10 mm
Lymph nodes by CT scan â‰¥ 15 mm --> measured in short axis
- Patients must be â‰¥ 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 â‰¥ 1.5 x 10^9/L Platelets â‰¥ 100 x 10^9/L Bilirubin â‰¤ 1.5 x ULN (upper limit
of normal) AST and ALT â‰¤ 2.5 x ULN; â‰¤ 4.0 x ULN if patient has liver metastases Serum
creatinine â‰¤ 1.5 x ULN or Creatinine clearance â‰¥ 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).
- Patients must have had at least 1 prior line of cytotoxic chemotherapy for breast
cancer, in any setting, which must have included an anthracycline and a taxane (unless
contraindicated). There is no limit to the number of prior chemotherapy regimens
- Patients may have received other therapies including endocrine therapy, immunotherapy,
and/or targeted therapies (including CDK4/6 inhibitors).
- Patients must have recovered (to at least grade 0 or 1) from all reversible toxicity
related to prior chemotherapy or systemic therapy and have adequate washout as
- Longest of one of the following:
- Two weeks,
- 5 half-lives for investigational agents
- Standard cycle length of standard therapies.
- Prior external beam radiation is permitted provided a minimum of 28 days (4 weeks)
have elapsed between the last dose of radiation and date of enrollment. Exceptions may
be made for low-dose, non-myelosuppressive radiotherapy after consultation with CCTG.
Concurrent radiotherapy is not permitted.
- Previous surgery is permitted provided that a minimum of 21 days (3 weeks) have
elapsed between any major surgery and date of enrollment and that wound healing has
- Patient consent must be appropriately obtained in accordance with applicable local and
regulatory requirements. Each patient must sign a consent form prior to enrollment in
the trial to document their willingness to participate.
- Patients must be accessible for treatment and follow up. Patients enrolled on this
trial must be treated and followed at the participating centre. This implies there
must be reasonable geographical limits (for example: 1 Â½ hour's driving distance)
placed on patients being considered for this trial.
- In accordance with CCTG policy, protocol treatment is to begin within 2 working days
of patient enrollment.
- Women of childbearing potential must have agreed to use a highly effective
- 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
- 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 â‰¥ 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
- 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