Description:
The standard or usual treatment for this disease is to undergo chemotherapy to slow the
spread of disease and relieve some symptoms of cancer. One of the standard types of
chemotherapy is a drug called paclitaxel (Taxol) given in a low dose every week for three out
of four weeks.
CFI-402257 is a new type of drug for breast cancer. Laboratory tests show that it may help
slow the growth of breast cancer. This drug has been shown to shrink tumours in animals.
CFI-402257 has been studied in a few people and appears well tolerated with little side
effects. CFI-402257 seems promising but it is not clear if it can offer better results when
given with paclitaxel compared to paclitaxel alone.
Title
- Brief Title: CFI-402257 in Combination With Paclitaxel in Patients With Advanced/Metastatic HER2-Negative Breast Cancer
- Official Title: A Phase Ib and Open Label Phase II Study of CFI-402257 in Combination With Weekly Paclitaxel in Patients With Advanced/Metastatic HER2-Negative Breast Cancer
Clinical Trial IDs
- ORG STUDY ID:
I236
- NCT ID:
NCT03568422
Conditions
Interventions
Drug | Synonyms | Arms |
---|
CFI-402257 | | CFI-402257 + Paclitaxel |
Paclitaxel | | CFI-402257 + Paclitaxel |
Purpose
The standard or usual treatment for this disease is to undergo chemotherapy to slow the
spread of disease and relieve some symptoms of cancer. One of the standard types of
chemotherapy is a drug called paclitaxel (Taxol) given in a low dose every week for three out
of four weeks.
CFI-402257 is a new type of drug for breast cancer. Laboratory tests show that it may help
slow the growth of breast cancer. This drug has been shown to shrink tumours in animals.
CFI-402257 has been studied in a few people and appears well tolerated with little side
effects. CFI-402257 seems promising but it is not clear if it can offer better results when
given with paclitaxel compared to paclitaxel alone.
Detailed Description
Phase I:
The purpose of the first phase of the study is to find the highest dose of CFI-402257 that
can be tolerated without causing very severe side effects when receiving paclitaxel. This is
done by starting at a dose lower than the one that is tolerated in patients when given on its
own. Participants are given CFI-402257 together with paclitaxel 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 new participants will be given a higher dose of CFI-402257.
Participants joining this study later on will get higher doses of CFI-402257 than
participants who join earlier. This will continue until a dose is found that causes severe
but temporary side effects. Doses higher than that will not be given.
Phase II:
The purpose of the second phase will be to find out the effect that CFI-402257 has on breast
cancer, using doses found to be safe in the first phase of the study, when given with
paclitaxel.
Trial Arms
Name | Type | Description | Interventions |
---|
CFI-402257 + Paclitaxel | Experimental | Oral CFI-402257 on intermittent schedule:* days 1, 2, 8, 9, 15 & 16 q4w Plus Paclitaxel 80 mg/m2 IV days 1, 8 & 15 every 28 days | |
Eligibility Criteria
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. 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 are willing is prior to treatment (after enrollment) and
again no later than the end of the day following the day 8 paclitaxel infusion.
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). 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 (e.g. at least 3 weeks for
capecitabine.
- 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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | Female |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Phase I: Safety and tolerability of CFI-402257 assessed by CTCAE |
Time Frame: | 2 years |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | Clinical benefit rate determined by complete response, partial response or stable disease |
Time Frame: | 2 years |
Safety Issue: | |
Description: | > 16 weeks in duration |
Measure: | Number and severity of adverse events by CTCAE |
Time Frame: | 2 years |
Safety Issue: | |
Description: | |
Measure: | Pharmacokinetic analysis (AUC) using ANOVA and linear regression or comparable nonparametric statistical methods will be used to make dose group comparisons. |
Time Frame: | 2 years |
Safety Issue: | |
Description: | |
Measure: | Pharmacokinetic analysis (Cmax) using ANOVA and linear regression or comparable nonparametric statistical methods will be used to make dose group comparisons. |
Time Frame: | 2 years |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Canadian Cancer Trials Group |
Last Updated
May 24, 2021