Clinical Trials /

CFI-400945 and Durvalumab in Patients With Advanced Triple Negative Breast Cancer

NCT04176848

Description:

The purpose of this study is to find out the effect that CFI-400945 and durvalumab have on breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: CFI-400945 and Durvalumab in Patients With Advanced Triple Negative Breast Cancer
  • Official Title: A Phase II Study of CFI-400945 and Durvalumab in Patients With Advanced/Metastatic Triple Negative Breast Cancer (TNBC)

Clinical Trial IDs

  • ORG STUDY ID: I239
  • NCT ID: NCT04176848

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
CFI-400945CFI-400945 + Durvalumab
DurvalumabCFI-400945 + Durvalumab

Purpose

The purpose of this study is to find out the effect that CFI-400945 and durvalumab have on breast cancer.

Detailed Description

      CFI-400945 is a new type of drug for breast cancer. Laboratory tests show that it works by
      blocking a specific protein called Polo-like Kinase 4 (PLK4) that is involved in cancer cell
      growth. CFI-400945 may slow down the growth of cancer cells or may cause cancer cells to die.
      This drug has been shown to shrink tumours in animals and has been studied in more than 60
      patients. It appears to be well tolerated with few side effects. CFI-400945 seems promising
      but it is not clear if it can offer better results than standard therapy.

      Durvalumab is a new type of drug for many types of cancer. Durvalumab is an immunotherapy
      drug and not a chemotherapy drug. Laboratory tests show that it works by allowing the immune
      system (PD-1 and PD-L1 interaction) to detect your cancer and reactivating the immune
      response. This may help to slow down the growth of cancer or may cause cancer cells to die.
      Durvalumab has been shown to shrink tumours in animals and has been studied in more than 6000
      people. In laboratory studies, when used together with CFI-400945, results seem promising but
      it is not clear if it can offer better results than standard treatment alone. This is the
      first time that the combination of CFI-400945 and durvalumab has been tested in patients.
    

Trial Arms

NameTypeDescriptionInterventions
CFI-400945 + DurvalumabExperimentalCycle 1: CFI-400945 orally on Days 1-7 (then 7 days off) and on Days 15-21 (then 7 days off) Cycle 2 on: CFI-400945 orally once daily and Durvalumab 1500mg IV on Day 1 (28 day cycles)
  • CFI-400945
  • Durvalumab

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have histologically and/or cytologically confirmed diagnosis of breast
             cancer, that is advanced/metastatic or unresectable, for which no curative therapy
             exists, and be negative for ER, PR and HER2 by ASCO/CAP criteria on the most recent
             sample. Patients with tumour with either low (< 10%) ER expression who are PR and HER2
             negative, or ER and HER2 negative but with low PR (< 10%) may be enrolled after
             discussion and confirmation with CCTG

          -  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 6 patients in Stage 1 and 10 in Stage 2 must have
             accessible disease suitable for biopsy, have provided informed consent for and be
             willing to undergo a tumour biopsy prior to treatment and again between cycle 3, Day
             1-8.

          -  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).

          -  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 and/or targeted
             therapies (including CDK4/6 inhibitors and PARP inhibitors).

          -  Patients may not have received prior immunotherapies of any kind, nor any agent
             targeting PLK4.

          -  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
             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.
             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
             occurred.

          -  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 ½ 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
             contraceptive method.

          -  Women of childbearing potential will have a pregnancy test to determine eligibility as
             part of the Pre-Study Evaluation; this may include an ultrasound to rule-out pregnancy
             if a false-positive is suspected

          -  Subjects should not donate blood while participating in this study, or for at least 90
             days following the last infusion of durvalumab

        Exclusion Criteria:

          -  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 serious illnesses or medical conditions which would not permit the
             patient to be managed according to the protocol (including corticosteroid
             administration), or would put the patient at risk. This includes but is not limited
             to:

               -  History of significant neurologic or psychiatric disorder which would impair the
                  ability to obtain consent or limit compliance with study requirements.

               -  Active infection requiring systemic therapy; (including any patient known to have
                  active hepatitis B, hepatitis C or human immunodeficiency virus (HIV) or
                  tuberculosis or any infection requiring systemic therapy).

               -  Active peptic ulcer disease or gastritis.

               -  Known pneumonitis or pulmonary fibrosis with clinically significant impairment of
                  pulmonary function.

               -  Patients with diabetes mellitus are eligible but must be clinically stable on
                  therapy (if applicable) and investigator and patient should be aware of the
                  potential risk of immune mediated pancreatic toxicity and B cell destruction.

          -  Patients are not eligible if they have a known hypersensitivity to the study drug(s)
             or their components.

          -  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 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 VI Table 1 are excluded. Patients
             being treated with drugs listed in Appendix VI Table 2 may be enrolled, but should be
             monitored carefully for toxicities resulting from potential interactions between
             CFI-400945 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.

          -  Active or prior documented autoimmune or inflammatory disorders including inflammatory
             bowel disease (e.g. colitis or Crohn's disease), diverticulitis with the exception of
             diverticulosis, celiac disease or other serious gastrointestinal chronic conditions
             associated with diarrhea), systemic lupus erythematosus, Sarcoidosis syndrome, or
             Wegener syndrome (granulomatosis with polyangiitis), rheumatoid arthritis,
             hypophysitis, uveitis, etc., within the past 3 years prior to the start of treatment.
             The following are exceptions to this criterion:

               -  Patients with alopecia.

               -  Patients with Grave's disease, vitiligo or psoriasis not requiring systemic
                  treatment (within the last 2 years).

               -  Patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on
                  hormone replacement.

          -  History of primary immunodeficiency, history of allogenic organ transplant that
             requires therapeutic immunosuppression and the use of immunosuppressive agents within
             28 days of enrollment *.

             * NOTE: Intranasal/inhaled corticosteroids or systemic steroids that do not to exceed
             10 mg/day of prednisone or equivalent dose of an alternative corticosteroid are
             permissible.

          -  Live attenuated vaccination administered within 30 days prior to enrollment or within
             30 days of receiving durvalumab.

          -  Any previous treatment with a PD-1 or PD-L1 inhibitor, including durvalumab or an
             anti-CTLA4.

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate of CFI-400945 given with durvalumab using RECIST 1.1
Time Frame:24 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Disease Control Rate of CFI-400945 given with Durvalumab
Time Frame:24 months
Safety Issue:
Description:(DCR, defined as CR or PR or stable disease (SD) > 16 weeks in duration)
Measure:Immune-Related Response Rate (iRECIST) of CFI-400945 given with durvalumab
Time Frame:24 months
Safety Issue:
Description:
Measure:Safety and Tolerability of CFI-400945 given orally in combination with durvalumab assessed by CTCAE
Time Frame:24 months
Safety Issue:
Description:
Measure:Immune effects of CFI-400945 + durvalumab measured in cfDNA
Time Frame:24 months
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Canadian Cancer Trials Group

Last Updated

November 22, 2019