Clinical Trials /

To Study Clinical Effectiveness and Safety of Olaparib Monotherapy in Metastatic Breast Cancer Patients.

NCT03286842

Description:

This open-label, multi-centre phase IIIb study will assess the effectiveness, benefits and potential harms in the use of olaparib monotherapy treatment for patients with HER2-ve metastatic breast cancer associated with germline or somatic breast cancer susceptibility gene (gBRCA1/2 or sBRCA1/2) mutations.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: To Study Clinical Effectiveness and Safety of Olaparib Monotherapy in Metastatic Breast Cancer Patients.
  • Official Title: A Phase IIIb, Single-arm, Open-label Multicentre Study of Olaparib Monotherapy in the Treatment of HER2-ve Metastatic Breast Cancer Patients With Germline BRCA1/2 Mutations.

Clinical Trial IDs

  • ORG STUDY ID: D0816C00018
  • NCT ID: NCT03286842

Conditions

  • HER2-ve Metastatic Breast Cancer
  • Germline BRCA1/2 Mutations

Interventions

DrugSynonymsArms
OlaparibOlaparib

Purpose

This open label, multi-centre phase IIIb study will assess the effectiveness, benefits and potential harms in the use of olaparib monotherapy treatment for patients with HER2-ve metastatic breast cancer associated with Germline breast cancer susceptibility gene (gBRCA1/2) mutations.

Detailed Description

      The study (LUCY) is a phase IIIb, multicenter, single-arm, open-label study designed to
      evaluate the clinical effectiveness in a real-world setting of olaparib monotherapy in
      patients with confirmed germline Breast Cancer susceptibility gene (gBRCA1/2) mutations. This
      study will generate additional data to support other olaparib studies, which may help inform
      and guide clinical practice. Physician defined progression-free survival is the primary
      outcome measure. Overall Survival will also be assessed and the data will be statistically
      compared with that from an observational study to analyze the comparative life prolongation
      attributed to olaparib therapy in patients with human epidermal growth factor receptor 2
      (HER2-ve), gBRCA1/2 mutation-positive metastatic breast cancer. Based on the prevalence of
      gBRCA1/2 mutations, it is estimated that up to 2500 patients may require screening in order
      to identify 250 patients. Patients will be administered two olaparib 150mg tablets in morning
      and evening of every day after a light meal. Dose reductions may be required for olaparib
      treatment related toxicities. Patients should continue to receive study treatment until
      documented physician-defined disease progression as assessed by the Investigator or
      unacceptable toxicity, or for as long as they do not meet any other discontinuation criteria.
      A positive benefit/risk profile is expected and no ethical issues are identified from
      exposing patients to olaparib within the planned clinical study.
    

Trial Arms

NameTypeDescriptionInterventions
OlaparibExperimentalOlaparib 150mg tablets administered orally twice daily continuously
  • Olaparib

Eligibility Criteria

        Inclusion Criteria

        1) Provision of informed consent prior to any study specific procedures. For patients aged
        <20 years and screened in Japan, a written informed consent should be obtained from the
        patient and his or her legally acceptable representative.

        2) Patients must be ≥18 years of age. 3) Histologically or cytologically confirmed HER2-ve
        breast cancer with evidence of metastatic disease. Patients can have either TNBC (defined
        as oestrogen receptor and progesterone receptor negative [immunohistochemistry nuclear
        staining <1%] and HER2-ve [immunohistochemistry 0, 1+ or 2+ and/or in situ hybridization
        non-amplified with ratio less than 2.0]) or oestrogen receptor / progesterone receptor
        positive breast cancer as long as they are HER2-ve.

        4) Documented BRCA1/2 (+ve) status, the patient must have a mutation that is predicted to
        be deleterious or suspected deleterious (known or predicted to be detrimental / lead to
        loss of function). Mutations that are not clearly pathogenic will be assessed by a
        committee of genetic specialists to adjudicate if the patient is eligible.

        5) Patients must have received a taxane or an anthracycline in either an adjuvant (may
        include neoadjuvant) or metastatic treatment setting. 6) Patients must not have received
        more than one prior line of chemotherapy in the metastatic setting. If a patient has
        oestrogen receptor and/or progesterone receptor positive HER2 negative metastatic breast
        cancer and has completed a prior line of hormonal treatment, then if the current or
        currently planned choice of treatment for the patient does not include a hormonal treatment
        then they would be a suitable patient to enter the study. Previous endocrine therapy could
        be in either an adjuvant or a metastatic setting and include endocrine therapy in
        combination with a targeted agent such as a CDK4/6 or mTOR inhibitor.

        7) Be considered suitable, by the Investigator, for further treatment with single-agent
        chemotherapy for the metastatic disease.

        8) Patients must have a life expectancy ≥ 16 weeks. Exclusion Criteria

          1. Previous enrolment in the present study.

          2. Participation in another clinical study with an investigational product (IP) during
             the last 1 month.

          3. Patients receiving any systemic chemotherapy or radiotherapy (except for palliative
             reasons) within 3 weeks prior to study treatment.

          4. Any previous treatment with a PARP inhibitor, including olaparib.

          5. Other malignancy within the last 5 years except: any breast cancer not considered HER2
             -ve/gBRCAm, adequately treated non-melanoma skin cancer, curatively treated in situ
             cancer of the cervix, ductal carcinoma in situ (DCIS), stage 1, grade 1 endometrial
             carcinoma, or other solid tumours including lymphomas (without bone marrow
             involvement) curatively treated with no evidence of disease for ≥5 years.

          6. Resting electrocardiogram (ECG) with corrected QT interval (QTc) > 470 msec on two or
             more time points within a 24-hour period or family history of long QT syndrome.

          7. Concomitant use of known strong (e.g., phenobarbital, enzalutamide, phenytoin,
             rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or
             moderate CYP3A inducers (e.g., bosentan, efavirenz, modafinil). The required washout
             period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3
             weeks for other agents.

          8. Patients with myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) or with
             features suggestive of MDS/AML.

          9. Patients with symptomatic uncontrolled brain metastases. Patients with previously
             treated stable brain metastases are eligible.

         10. Patients with known active hepatitis (B or C) due to risk of transmitting the
             infection through blood or other body fluids.

         11. Previous allogenic bone marrow transplant or double umbilical cord blood
             transplantation (dUCBT).

         12. Whole blood transfusions in the last 120 days prior to entry to the study (packed red
             blood cells and platelet transfusions are acceptable).
      
Maximum Eligible Age:130 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival in real-world setting
Time Frame:At every visit until the earliest of disease progression, death or end of study for up to 3 years.
Safety Issue:
Description:Progression-free survival is defined as the time from the first dose of olaparib to physician-defined progression or death from any cause (in the absence of progression). Physician-defined progression can be RECIST progression, symptomatic progression, or clear progression of non measurable disease, as long as there is some manner of documenting all of them.

Secondary Outcome Measures

Measure:Overall Survival (OS)
Time Frame:At every visit/follow-up from day 1 until death or end of study for up to 3 years.
Safety Issue:
Description:Overall survival is defined as the time from first dose of olaparib to the date of death from any cause.
Measure:Time to first subsequent treatment or death (TFST)
Time Frame:At every visit from day 1 until start of first subsequent anticancer treatment or death or end of study for up to 3 years.
Safety Issue:
Description:Time to first subsequent treatment or death is defined as the time from first dose of olaparib to first subsequent treatment commencement or death if this occurs before commencement of first subsequent treatment.
Measure:Time to second subsequent treatment or death (TSST)
Time Frame:At every visit from day 1 until start of second subsequent anticancer treatment or death or end of study for up to 3 years.
Safety Issue:
Description:Time to second subsequent treatment or death is defined as the time from first dose of olaparib to second subsequent treatment commencement or death if this occurs before commencement of second subsequent treatment.
Measure:Time to study treatment discontinuation or death (TDT)
Time Frame:At every visit from day 1 until discontinuation of study treatment or death or end of study for up to 3 years.
Safety Issue:
Description:Time to study treatment discontinuation or death is, defined as the time from first dose of olaparib to study treatment discontinuation or death if this occurs before discontinuation of study treatment.
Measure:Time to second progression or death (PFS2)
Time Frame:At baseline and at every visit until second progression or death or end of study for up to 3 years.
Safety Issue:
Description:PFS2 is defiend as the time from first dose of olaparib to the earliest progression event subsequent to that used for the primary variable PFS or death from any cause.
Measure:Clinical response rate (CRR)
Time Frame:At baseline and at every visit until disease progression or death or end of study for up to 3 years.
Safety Issue:
Description:CRR is defined as the proportion of patients assessed by the Investigator as responding (physician-defined response, radiological [e.g. RECIST] or symptomatic)
Measure:Duration of clinical response (DoCR)
Time Frame:At baseline and at every visit until disease progression or death or end of study for up to 3 years.
Safety Issue:
Description:DoCR is defined as the time from the date the Investigator first assessed the patient as responding to the date the Investigator assessed the patient as progressing or the date of death from any cause (in the absence of progression).
Measure:Safety and tolerability of olaparib by assessment of adverse events.
Time Frame:At baseline, every visit/follow-up from day 1 until 30 days post last dose of study treatment.
Safety Issue:
Description:Assessment of adverse events (AEs), graded by Common Terminology Criteria for Adverse Event (CTCAE).
Measure:Laboratory assessment of Haematology.
Time Frame:At every visit up to and including 30 days post last dose of study medication.
Safety Issue:
Description:To assess the hematology (haemoglobin, leukocyte count, absolute neutrophil count, absolute lymphocyte count, platelet count, and mean cell volume [MCV]) as a criteria of safety and tolerability of olaparib.
Measure:Laboratory assessment of clinical chemistry.
Time Frame:At screening, visit 2, as clinically indicated while on treatment, at treatment discontinuation and at 30 days post treatment discontinuation.
Safety Issue:
Description:To assess the clinical chemistry (creatinine, bilirubin total, alkaline phosphatase, aspartate transaminase, albumin, potassium, sodium, calcium, blood urea nitrogen, and total protein) as a criteria of safety and tolerability of olaparib.
Measure:Laboratory assessment of urinalysis.
Time Frame:At screening and post treatment 30 days follow-up.
Safety Issue:
Description:To assess urinalysis (Hemoglobin/erythrocytes/blood, protein/albumin, and glucose) as a criteria of safety and tolerability of olaparib.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

  • HER2-ve metastatic breast cancer.
  • Germline BRCA1/2 mutations.
  • BRCA1
  • BRCA2

Last Updated

January 23, 2018