Clinical Trials /

Effect of Pembrolizumab and Cisplatin on Metastatic, Locally Recurrent or Inoperable Triple-Negative Breast Cancer

NCT03644589

Description:

This is a Phase II treatment study that is done to evaluate how effective and safe the combination of pembrolizumab and cisplatin work in treating participants with triple-negative breast cancer that had spread to other parts of the body, has come back, or cannot be removed by surgery. Pembrolizumab (investigational drug) is a monoclonal antibody that works by helping your immune system to fight cancer. Cisplatin is a chemotherapy drug that works by interfering with tumor cell division. Studies also suggest that treatment with chemotherapy, like cisplatin, may improve the effectiveness of pembrolizumab. This study will test the effectiveness of pembrolizumab and cisplatin in participants with advanced triple-negative breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Withdrawn

Phase:

Phase 2

Trial Eligibility

Document

Title

    <li>Brief Title: Effect of Pembrolizumab and Cisplatin on Metastatic, Locally Recurrent or Inoperable Triple-Negative Breast Cancerli><li>Official Title: A Phase II Trial Evaluating Safety and Efficacy of Pembrolizumab and Cisplatin in Patients With Advanced Triple Negative Breast Cancerli>

Clinical Trial IDs

    <li>ORG STUDY ID: RG1718047li><li>SECONDARY ID: 9852/MK-3475-315li><li>NCT ID: NCT03644589li>

Conditions

    <li>Estrogen Receptor Negativeli><li>HER2/Neu Negativeli><li>Metastatic Breast Cancerli><li>Progesterone Receptor Negativeli><li>Recurrent Breast Carcinomali><li>Triple Negative Breast Cancerli>

Interventions

<td>Pembrolizumabtd><td>Immunoglobulin G4, Anti-(Human Programmed Cell Death 1), MK-3475td><td>Treatment (pembrolizumab, cisplatin)td><td>Cisplatintd><td>CDDPtd><td>Treatment (pembrolizumab, cisplatin)td>
DrugSynonymsArms

Purpose

This is a Phase II treatment study that is done to evaluate how effective and safe the combination of pembrolizumab and cisplatin work in treating participants with triple-negative breast cancer that has spread to other parts of the body, has come back, or cannot be removed by surgery. Pembrolizumab (investigational drug) is a monoclonal antibody that works by helping your immune system to fight cancer. Cisplatin is a chemotherapy drug that works by interfering with tumor cell division. Studies also suggest that treatment with chemotherapy, like cisplatin, may improve the effectiveness of pembrolizumab. This study will test the effectiveness of pembrolizumab and cisplatin in participants with advanced triple-negative breast cancer.

Detailed Description

      Participants will receive pembrolizumab intravenously (IV) over 30 minutes and cisplatin once
      every 3 weeks for a total of 6 doses. Both drugs are given by vein (Intravenous(IV)) on day
      1. Participants that are responding to the study treatment will continue to receive
      pembrolizumab alone for up to 24 months until disease gets worse, having bad side effects, no
      longer wish to be in the study, or have become pregnant (whichever comes first).

      In addition to study drug administration visits, participants will be asked to have physical
      exams, blood draws every three weeks and tumor evaluation using MRI or CT scans every 9
      weeks.

      After completion of study treatment, participants are followed up for safety within at 30
      days of last dose of study treatment and then every 12 weeks until study completion.
    

Trial Arms

<td>Treatment (pembrolizumab, cisplatin)td><td>Experimentaltd><td>Participants receive pembrolizumab and cisplatin once every 3 weeks for a total of 6 doses. Both drugs are given by vein (IV). Participants that are responding to the study treatment will continue to receive pembrolizumab alone beyond 6 cycles for up to 24 months until disease gets worse, having bad side effects, no longer wish to be in the study, or have become pregnant (whichever comes first). Participants receive pembrolizumab over 30 minutes and cisplatin on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Participants without disease progression after 6 courses may continue on pembrolizumab IV on day 1 every 21 days for up to 24 months (or 35 courses) in the absence of disease progression or unacceptable toxicity.td><td>
    <li>Cisplatinli>
td>
NameTypeDescriptionInterventions

Eligibility Criteria

        Inclusion Criteria:

          -  Have histologically confirmed diagnosis of metastatic or locally recurrent and
             inoperable triple negative breast cancer (estrogen receptor [ER] < 10%, progesterone
             receptor [PR] < 10% and HER2 negative by IHC or fluorescence in situ hybridization
             [FISH]).

          -  Be willing and able to provide written informed consent for the trial.

          -  Have measurable disease based on RECIST 1.1.

          -  Be willing to provide tissue from a newly obtained core or excisional biopsy of a
             tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days)
             prior to initiation of treatment on day 1. Participants for whom newly-obtained
             samples cannot be provided (e.g. inaccessible or participant safety concern) may
             submit an archived specimen only upon agreement from the principal investigator. *
             Participants that are screening for second course phase (retreatment period) do not
             need to comply with the tumor tissue collection eligibility criteria.

          -  Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
             performance scale. Evaluation of ECOG is to be performed within 10 days prior to the
             date of treatment initiation.

          -  Absolute neutrophil count (ANC) >= 1500/uL, performed within 10 days of treatment
             initiation.

          -  Platelets >= 100 000/uL, performed within 10 days of treatment initiation.

          -  Hemoglobin >= 9.0 g/dL or >= 5.6 mmol/L, performed within 10 days of treatment
             initiation.

          -  Creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine
             clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or
             creatinine clearance [CrCl]) >= 30 mL/min for participant with creatinine levels > 1.5
             x institutional ULN, performed within 10 days of treatment initiation.

          -  Total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for participants with total
             bilirubin levels > 1.5 x ULN, performed within 10 days of treatment initiation.

          -  Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase ([SGOT]) and
             alanine aminotransferase (ALT) serum glutamate pyruvate transaminase ([SGPT]) =< 2.5 x
             ULN (=< 5 x ULN for participants with liver metastases), performed within 10 days of
             treatment initiation.

          -  International normalized ratio (INR) OR prothrombin time (PT) =< 1.5 x ULN unless
             participant is receiving anticoagulant therapy as long as PT or activated partial
             thromboplastin time (aPTT) is within therapeutic range of intended use of
             anticoagulants, performed within 10 days of treatment initiation.

          -  Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless participant is
             receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of
             intended use of anticoagulants, performed within 10 days of treatment initiation.

          -  Female participants of childbearing potential should have a negative serum pregnancy
             test performed at the screening visit and a urine pregnancy test performed on cycle 1
             day 1 (within 72 hours of receiving the first dose of study medication). If the urine
             test is positive or cannot be confirmed as negative, a serum pregnancy test will be
             required.

          -  A female participant is eligible to participate if she is not pregnant, not
             breastfeeding, and at least one of the following conditions applies: * Not a woman of
             childbearing potential (WOCBP), OR * A WOCBP who agrees to follow the contraceptive
             guidance during the treatment period and for at least 120 days after the last dose of
             study treatment. ** Note: abstinence is acceptable if this is the usual lifestyle and
             preferred contraception for the participant.

          -  A male participant must agree to use a contraception during the treatment period and
             for at least 120 days after the last dose of study treatment and refrain from donating
             sperm during this period. * Note: abstinence is acceptable if this is the usual
             lifestyle and preferred contraception for the participant.

        Exclusion Criteria:

          -  Has received greater than 3 lines of cytotoxic chemotherapy for metastatic breast
             cancer.

          -  Documented disease progression on prior cisplatin therapy.

          -  Is currently participating in or has participated in a study of an investigational
             agent or using an investigational device within 4 weeks of the first dose of
             treatment. * Note: participants who have entered the follow-up phase of an
             investigational study may participate as long as it has been 4 weeks after the last
             dose of the previous investigational agent.

          -  Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
             (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
             immunosuppressive therapy within 7 days prior to the first dose of study drug.

          -  Has had a prior monoclonal antibody within 4 weeks prior to study day 1 or who has not
             recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents
             administered more than 4 weeks earlier.

          -  Has received prior systemic anti-cancer therapy including investigational agents
             within 2 weeks prior to first dose of study treatment. * Note: participants must have
             recovered from all adverse events (AEs) due to previous therapies to =< grade 1 or
             baseline. Participants with =< grade 2 neuropathy may be eligible. * Note: if
             participant received major surgery, they must have recovered adequately from the
             toxicity and/or complications from the intervention prior to starting study treatment.

          -  Has a known additional malignancy that is progressing or requires active treatment.
             Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the
             skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that has
             undergone potentially curative therapy.

          -  Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis. Participants with previously treated brain metastases may participate
             provided they are radiologically stable, i.e. without evidence of progression for at
             least 4 weeks by repeat imaging (note that the repeat imaging should be performed
             during study screening), clinically stable and without requirement of steroid
             treatment for at least 14 days prior to first dose of study treatment.

          -  Has severe hypersensitivity (>= grade 3) to pembrolizumab and/or any of its
             excipients.

          -  Has received prior radiotherapy within 2 weeks of start of study treatment.
             Participants must have recovered from all radiation-related toxicities, not require
             corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted
             for palliative radiation (=< 2 weeks of radiotherapy) to non-CNS disease.

          -  Has active autoimmune disease that has required systemic treatment in the past 2 years
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
             drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
             form of systemic treatment.

          -  Has a history of (non-infectious) pneumonitis that required steroids or has current
             pneumonitis.

          -  Has an active infection requiring systemic intravenous therapy.

          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the trial, interfere with the participant's
             participation for the full duration of the trial, or is not in the best interest of
             the participant to participate, in the opinion of the treating investigator.

          -  Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

          -  A WOCBP who has a positive urine pregnancy test within 72 hours prior to first dose of
             study treatment. If the urine test is positive or cannot be confirmed as negative, a
             serum pregnancy test will be required.

          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the pre-screening or screening visit
             through 120 days after the last dose of trial treatment.

          -  Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with
             an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g.,
             CTLA-4, OX 40, CD137).

          -  Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).

          -  Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg]
             reactive) or known active hepatitis C virus (defined as hepatitis C virus [HCV]
             ribonucleic acid (RNA) [qualitative] is detected) infection. * Note: no testing for
             hepatitis B and hepatitis C is required unless mandated by local health authority.

          -  Has received a live vaccine within 30 days prior to the first dose of trial treatment.
      
<td>Maximum Eligible Age:td><td>N/Atd><td>Minimum Eligible Age:td><td>18 Yearstd><td>Eligible Gender:td><td>Alltd><td>Healthy Volunteers:td><td>Notd>

Primary Outcome Measures

<td>Measure:td><td>Overall response rate per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteriatd><td>Time Frame:td><td>Up to 3 yearstd><td>Safety Issue:td><td/><td>Description:td><td>Defined as the proportion of participants in the analysis population who have a complete response or partial response at any time during the study. A Simon two-stage optimal design will be used to assess whether the observed response rate is statistically significantly (at the one-sided significance level of .10) higher than the fixed historical benchmark of 25%.td>

Secondary Outcome Measures

<td>Measure:td><td>Overall response rate by Immune-Related Response Evaluation Criteria in Solid Tumorstd><td>Time Frame:td><td>Up to 3 yearstd><td>Safety Issue:td><td/><td>Description:td><td>(irRECIST)td>
<td>Measure:td><td>Disease Control Ratetd><td>Time Frame:td><td>Up to 3 yearstd><td>Safety Issue:td><td/><td>Description:td><td>Measured by RECIST and irRECISTtd>
<td>Measure:td><td>Duration of response per RECIST and irRECISTtd><td>Time Frame:td><td>Up to 3 yearstd><td>Safety Issue:td><td/><td>Description:td><td>Cumulative incidence estimates will be used. Disease control rate (DCR) by RECIST 1.1 and irRECIST.td>
<td>Measure:td><td>Duration of response (DoR) by RECIST 1.1 and irRECIST Progression-free survivaltd><td>Time Frame:td><td>Up to 3 yearstd><td>Safety Issue:td><td/><td>Description:td><td>Kaplan-Meier estimates will be used.td>
<td>Measure:td><td>Progression-free survival by RECIST 1.1 and irRECIST criteria.Overall survivaltd><td>Time Frame:td><td>Up to 3 yearstd><td>Safety Issue:td><td/><td>Description:td><td>Kaplan-Meier estimates will be used.td>
<td>Measure:td><td>Overall survival (OS) in participants with advanced TNBC treated with pembrolizumab and cisplatintd><td>Time Frame:td><td>Up to 10 yearstd><td>Safety Issue:td><td/><td>Description:td><td/>

Details

<td>Phase:td><td>Phase 2td><td>Primary Purpose:td><td>Interventionaltd><td>Overall Status:td><td>Not yet recruitingtd><td>Lead Sponsor:td><td>University of Washingtontd>

Trial Keywords

    <li>Cisplatinli><li>Pembrolizumabli><li>Keytrudali><li>Triple Negative Breast Cancerli><li>Immune-Checkpoint Inhibitorli><li>Metastatic Breast Cancerli><li>Breast Carcinomali><li>Recurrent Breast Cancerli>

Last Updated

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