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Treatment With Oral LY3023414 To Inhibit Homologous Recombination Followed By Prexasertib

NCT04032080

Description:

This study evaluates efficacy of LY3023414 followed by prexasertib in patients with metastatic triple negative breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Treatment With Oral LY3023414 To Inhibit Homologous Recombination Followed By Prexasertib
  • Official Title: Pilot Clinical Trial Of Treatment With Oral LY3023414 To Inhibit Homologous Recombination (HR) Followed By Prexasertib In Patients With Chemotherapy-Pretreated Metastatic Triple Negative Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: 018-745
  • NCT ID: NCT04032080

Conditions

  • Triple Negative Breast Cancer

Interventions

DrugSynonymsArms
Drug 1: LY3023414; Drug 2: PrexasertibLY3023414 followed by prexasertib

Purpose

This study evaluates efficacy of LY3023414 followed by prexasertib in patients with metastatic triple negative breast cancer.

Detailed Description

      Seventy to eighty percent of breast cancers have a gene expression profile which is
      characterized by homologous recombination deficiency (HRD) and high proliferation. HRD leads
      to errors in DNA pathway [non -homologous end joining (NHEJ)] that repair DNA-breaks, a
      process required for metastatic triple negative breast cancer (TNBC) survival. The hypothesis
      of this pilot trial is that administration of LY3023414 will inhibit NHEJ in metastatic TNBC,
      leading at the time of disease progression to metastases that are HR-deficient and sensitive
      to prexasertib therapy.
    

Trial Arms

NameTypeDescriptionInterventions
LY3023414 followed by prexasertibExperimentalPatients with metastatic TNBC who meet the enrollment criteria will receive LY3023414 until disease progression followed by prexasertib until disease progression. Patients who achieve a confirmed clinical complete response will discontinue prexasertib, and these patients will be followed to document the durability of the complete responses. Patients whose disease does not respond to prexasertib may be treated with standard of care breast cancer therapies off study, at the recommendation of the treating physician.
  • Drug 1: LY3023414; Drug 2: Prexasertib

Eligibility Criteria

        Inclusion Criteria:

          1. Patients ≥18 years of age. Patients must agree to use one highly effective (less than
             1% failure rate) method of contraception or use a combination of two effective methods
             of contraception during treatment with study drug and for at least 12 weeks following
             the last dose of study drug.

          2. Have a diagnosis of metastatic TNBC previously treated with standard anthracycline,
             cyclophosphamide, and taxane chemotherapy, unless there was a contraindication to
             doxorubicin, in which case prior treatment with this agent is not required.

          3. Have not received more than 3 prior chemotherapy regimens for metastatic disease.
             Prior platinum and/or taxane therapy in the adjuvant or metastatic setting is
             permitted.

          4. Have locoregional (eg, breast, chest wall, regional lymphatic) or pulmonary or hepatic
             metastatic disease that is amenable to core needle biopsy. If a research biopsy from a
             patient's metastatic disease cannot be safely obtained, a skin biopsy is permitted. If
             a skin biopsy cannot be safely obtained, patients may still be eligible, per physician
             discretion.

          5. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (See
             Appendix I)

          6. Have adequate hematologic function, defined by:

               1. Absolute neutrophil count (ANC) >1500/mm3

               2. Platelet count ≥100,000/mm3

               3. Hemoglobin ≥9 g/dL

          7. Have adequate liver function, defined by:

               1. AST and ALT ≤2.5 x the upper limit of normal (ULN) or ≤5 x ULN in presence of
                  liver metastases

               2. Total bilirubin ≤1.5 x ULN

          8. Have adequate renal function, defined by:

             a. Serum creatinine ≤1.5 x ULN or calculated creatinine clearance of ≥60 ml/min

          9. Have the ability to swallow oral medications

         10. Patients who have a history of brain metastasis are eligible for the study provided
             that all the following criteria are met:

               1. Brain metastases which have been treated

               2. Off-treatment with steroids for 2 weeks before administration of the first dose
                  of LY3023414

               3. No ongoing requirement for dexamethasone or anti-epileptic drugs

               4. No clinical or radiological evidence of progression of brain metastases

         11. Patient must be accessible for treatment and follow-up.

         12. All patients must be able to understand the investigational nature of the study and
             give written informed consent prior to study entry.

        Exclusion Criteria:

          1. Have a family history of long QT Syndrome and serious cardiac conditions.

          2. Have QTcF interval of >470 msec on screening electrocardiogram (ECG) as well as on
             pre-dose Cycle 1 Day 1 ECG

          3. Have insulin-dependent diabetes mellitus. Patients with a type 2 diabetes mellitus are
             eligible if adequate control of blood glucose level is obtained by oral anti-diabetics
             as documented by HbA1c <8%. Patients with type 1 diabetes mellitus are not eligible.

          4. Previous radiotherapy for metastatic disease completed <2 weeks prior to study
             treatment initiation.

          5. Women who are pregnant or lactating.

          6. Patients who have any severe and/or uncontrolled medical conditions or other
             conditions that could affect their participation such as:

               1. severe impaired lung functions as defined as spirometry and DLCO that is 50% of
                  the normal predicted value and/or O2 saturation that is 88% or less at rest on
                  room air

               2. liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class
                  C).

               3. viral hepatitis or HIV.

          7. Concurrent use of CYP3A4 inhibitors and inducers from 72 hours prior to initiation of
             study treatment until the end of treatment.

          8. History of any other disease, physical examination finding, or clinical laboratory
             finding giving reasonable suspicion of a disease or condition that contraindicates use
             of an investigational drug, or that might affect interpretation of the results of this
             study, or render the patient at high risk for treatment complications.

          9. Patients who have received prior PI3K or CHK therapy.

         10. Any other investigational or anti-cancer treatments while participating in this study

         11. Any other active malignancy.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Efficacy (objective response rate)
Time Frame:Through study completion, 18 months
Safety Issue:
Description:To assess the objective response rate (CR+PR) associated with LY3023414 followed by prexasertib in metastatic TNBC patients.

Secondary Outcome Measures

Measure:Efficacy (duration of response)
Time Frame:through study completion, 18 months]
Safety Issue:
Description:To assess duration of response associated with sequential treatment of LY3023414 followed by prexasertib.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Baylor Research Institute

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