Clinical Trials /

CFI-402257 in Combination With Paclitaxel in Patients With Advanced/Metastatic HER2-Negative Breast Cancer

NCT03568422

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

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

  • Breast Cancer

Interventions

DrugSynonymsArms
CFI-402257CFI-402257 + Paclitaxel
PaclitaxelCFI-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

NameTypeDescriptionInterventions
CFI-402257 + PaclitaxelExperimentalOral 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
  • CFI-402257
  • Paclitaxel

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

          -  Presence of clinically and/or radiologically documented disease. All radiology studies
             must be performed within 21 days prior to registration (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 chemotherapy
                  (patients who relapse within 6 months of a taxane-containing regimen are not
                  eligible as deemed to be taxane-resistant/refractory) or;

               2. they have received taxane and/or anthracycline-containing adjuvant chemotherapy
                  or;

               3. they have a documented contraindication to chemotherapy other than weekly
                  paclitaxel.

          -  Patients must not be considered appropriate for endocrine therapy.

          -  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 registration. 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 registration, 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 registration.

        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 with significant cardiac (including uncontrolled hypertension) or pulmonary
             disease, or active CNS disease or infection.

          -  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:Not yet recruiting
Lead Sponsor:Canadian Cancer Trials Group

Last Updated