Eligibility Details:
Inclusion Criteria:
- 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, and for which systemic therapy is indicated. 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
- 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). For
phase Ib, patients are not required to have measurable disease as defined by RECIST
1.1 but must not have bone-only or marker only disease. For phase II, all patients
must have measurable disease as defined by RECIST 1.1. The criteria for defining
measurable disease are as follows:
Chest xray ≥ 20mm; CT scan ≥ 10mm (longest diameter); Physical exam ≥10mm; Lymph nodes by
CT scan ≥ 15mm (measured in short axis)
- Patients must be ≥18 years of age.
- Patients must have an ECOG performance status of 0 or 1.
- Patients must be able to swallow oral medications
- Patients must have received at least one non-taxane containing chemotherapy regimen
for advanced or metastatic disease unless:
1. they have relapsed within 6 months of completion of adjuvant/neoadjuvant
chemotherapy and the regiment did not contain taxane, or,
2. they have received taxane and/or anthracycline-containing adjuvant/neoadjuvant
chemotherapy 6 or more months prior to relapse or;
3. they have a documented contraindication to palliative chemotherapy other than
weekly paclitaxel.
- Patients must not be considered appropriate for endocrine therapy and must not have
received taxanes in the metastatic setting.
- Patients may have received other therapies including endocrine therapy, immunotherapy,
and/or targeted therapies (including CDK4/6 inhibitors).
- Patient may NOT have had previous exposure to any therapy within the pharmacological
class (TTK/MPS1 inhibitor).
- Patients must have recovered (to at least grade 0 or 1) from all reversible toxicity
other than alopecia related to prior chemotherapy or systemic therapy and have
adequate washout as follows:
- 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.
- Previous surgery is permitted provided that a minimum of 21 days (3 weeks) have
elapsed between any major surgery and date of enrollment, and wound healing has
occurred.
- Absolute neutrophils ≥ 1.5 x 10^9/L
- Platelets ≥100 x 10^9/L
- Bilirubin ≤ 1.0 x ULN
- AST and ALT ≤3.0 x ULN and ≤ 5.0 x ULN (if patient has liver mets)
- Serum creatinine ≤ 1.5 x ULN or
- Creatinine clearance ≥ 60mL/min
- Women of childbearing potential must have agreed to use a highly effective
contraceptive method
- 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.
- In accordance with CCTG policy, protocol treatment is to begin within 2 working days
of patient enrollment.
Exclusion Criteria:
- Patients with a history of other untreated malignancies or malignancies which required
therapy within the past 2 years. Patients with other malignancies of a nature that do
not require treatment may be eligible after consultation with the CCTG.
- Patients with HER2 positive breast cancer.
- 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 who have experienced untreated and/or uncontrolled cardiovascular conditions
and/or have symptomatic cardiac dysfunction (unstable angina, congestive heart
failure, myocardial infarction within the previous year or cardiac ventricular
arrhythmias requiring medication, history of 2nd or 3rd degree atrioventricular
conduction defects). Patients with a significant cardiac history, even if controlled,
should ahve a LVEF ≥ 50%
- Patients are not eligible if they have a known hypersensitivity to the study drug(s)
or their components.
- Patients with history of central nervous system metastases or spinal cord compression
unless have received definitive treatment, are clinically stable and do not require
corticosteroids.
- Patients who have contraindications to treatment with paclitaxel and/or neuropathy >
grade 1.
- Concurrent treatment with other investigational drugs or anti-cancer therapy.
- Pregnant or breastfeeding women.
- Prohibited medications as listed in Appendix V Table 1
- Patients 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.
- Patients with a medical condition that could impair the administration of oral agents
including significant bowel resection, inflammatory bowel disease or uncontrolled
nausea or vomiting.
common.study.methods.has-drugs-yes
common.study.methods.is-healthy-yes
