Clinical Trials /

Pembrolizumab in Treating Patients With Stage IV Metastatic or Recurrent Inflammatory Breast Cancer or Triple-Negative Breast Cancer Who Have Achieved Clinical Response or Stable Disease to Prior Chemotherapy

NCT02411656

Description:

This phase II trial studies how well pembrolizumab works in treating patients with stage IV inflammatory breast cancer or triple-negative breast cancer that has spread to other places in the body (metastatic) or has come back (recurrent), and who have achieved clinical response or stable disease to prior chemotherapy. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Related Conditions:
  • Breast Carcinoma
  • Inflammatory Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab in Treating Patients With Stage IV Metastatic or Recurrent Inflammatory Breast Cancer or Triple-Negative Breast Cancer Who Have Achieved Clinical Response or Stable Disease to Prior Chemotherapy
  • Official Title: A Phase II Study of Anti-PD-1 (MK-3475) Therapy in Patients With Metastatic Inflammatory Breast Cancer (IBC) or Non-IBC Triple Negative Breast Cancer (TNBC) Who Have Achieved Clinical Response or Stable Disease to Prior Chemotherapy

Clinical Trial IDs

  • ORG STUDY ID: 2014-0533
  • SECONDARY ID: NCI-2015-00671
  • SECONDARY ID: 2014-0533
  • NCT ID: NCT02411656

Conditions

  • Edema
  • Erythema
  • Estrogen Receptor Negative
  • HER2/Neu Negative
  • Peau d'Orange
  • Progesterone Receptor Negative
  • Recurrent Inflammatory Breast Carcinoma
  • Stage IV Inflammatory Breast Carcinoma
  • Triple-Negative Breast Carcinoma

Interventions

DrugSynonymsArms
PembrolizumabKeytruda, Lambrolizumab, MK-3475, SCH 900475Treatment (pembrolizumab)

Purpose

This phase II trial studies how well pembrolizumab works in treating patients with stage IV inflammatory breast cancer or triple-negative breast cancer that has spread to other places in the body (metastatic) or has come back (recurrent), and who have achieved clinical response or stable disease to prior chemotherapy. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To assess the efficacy of pembrolizumab (MK-3475) as a single agent in patients with
      metastatic inflammatory breast cancer (IBC) and non-IBC triple-negative breast cancer (TNBC).

      EXPLORATORY OBJECTIVES:

      I. To investigate the association between biomarkers in the peripheral blood and tumor
      tissue, such as PD-L1 expression, with safety and efficacy for IBC or non-IBC TNBC patients
      treated with MK-3475.

      II. To determine the disease control rate of metastatic IBC or non-IBC TNBC patients who have
      achieved clinical response or stable disease to the systemic therapy.

      III. To investigate the association between biomarkers and efficacy by ribonucleic acid
      (RNA)-sequencing of exosomes in blood and tumor for IBC or non-IBC TNBC patients.

      OUTLINE:

      Patients receive pembrolizumab intravenously (IV) over approximately 30 minutes on day 1.
      Courses repeat every 21 days for up to 24 months in the absence of disease progression or
      unacceptable toxicity.

      After completion of study treatment, patients are followed up at approximately 1 and 3
      months.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (pembrolizumab)ExperimentalPatients receive pembrolizumab IV over approximately 30 minutes on day 1. Courses repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

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

          -  Has histological confirmation of HER2 normal breast carcinoma with a clinical
             diagnosis of IBC based on presence of inflammatory changes in the involved breast,
             including diffuse erythema and edema (peau d'orange), with or without an underlying
             palpable mass involving the majority of the skin of the breast; pathological evidence
             of dermal lymphatic invasion should be noted but is not required for diagnosis of
             inflammatory breast cancer regardless estrogen receptor (ER)/progesterone receptor
             (PR) status; OR has histological confirmation of triple negative breast carcinoma
             (HER2 normal, ER/PR < 10%) without clinical diagnosis of IBC

          -  Has stage IV or recurrent disease that has been treated

          -  Has clinical response or stable disease for minimum of two months (three cycles of
             every three week chemotherapy or 8 weeks of weekly regimen, etc.) after receiving any
             prior chemotherapy for metastatic/recurrent disease; a minimum of two cycles (6-8
             weeks) of chemotherapy is required to determine clinical response; per Response
             Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1, clinical response for
             measurable disease is defined as complete response (CR) or partial response (PR); for
             non-measurable disease only (i.e. bone metastasis, ascites, pleural effusion, and
             pathological lymph nodes >= 10 to < 15 mm short axis) is defined as persistence of one
             or more non-target lesion(s) and no increase in overall tumor burden

          -  Is HER2 normal, defined as HER2 0 or 1+ by immunohistochemistry (IHC) and negative by
             fluorescence in situ hybridization (FISH) if performed; or HER2 is 2+ by IHC and
             negative by FISH; or HER2 negative by FISH if IHC is not performed

          -  Has a performance status of 0-1 on the Eastern Cooperative Oncology Group (ECOG)
             performance scale

          -  Absolute neutrophil count (ANC) >= 1,500/mcL

          -  Platelets >= 100,000 /mcL

          -  Hemoglobin (Hgb) >= 9 g/dL

          -  Creatinine levels < 1.5 x upper limit of normal (ULN)

          -  Total bilirubin =< 1.5 x ULN

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN or =<
             5 x ULN for subjects with liver metastases

          -  Subjects of childbearing potential should be willing to use effective methods of birth
             control or be surgically sterile, or abstain from heterosexual activity for the course
             of the study through at least 4 months after the last dose of study drug; subjects of
             childbearing potential are those who have not been surgically sterilized or have not
             been free from menses for > 1 year; effective methods of birth control include:

               -  Use of hormonal birth control methods: pills, shots/injections, implants (placed
                  under the skin by a health care provider), or patches (placed on the skin)

               -  Intrauterine devices (IUDs)

               -  Using 2 barrier methods (each partner must use 1 barrier method) with a
                  spermicide; males must use the male condom (latex or other synthetic material)
                  with spermicide; females must choose either a diaphragm with spermicide, or
                  cervical cap with spermicide, or a sponge (spermicide is already in the
                  contraceptive sponge)

          -  Has negative serum or urine pregnancy test for subjects of childbearing potential

        Exclusion Criteria:

          -  Is currently participating in a study of an investigational anti-cancer agent

          -  Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
             other form of immunosuppressive therapy

          -  Has not recovered from adverse events due to prior therapies, i.e. monoclonal
             antibody, chemotherapy, targeted small molecule therapy, radiation therapy, or
             surgery; (Note: subjects with grade 2 neuropathy, alopecia and general disorders and
             administration site conditions [per Common Terminology Criteria for Adverse Events
             (CTCAE) version 4.0] are an exception to this criterion and may qualify for the study)

          -  Has a known malignancy (other than breast cancer) except basal cell carcinoma or
             squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone
             potentially curative therapy

          -  Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis; subjects with previously treated brain metastases may participate if they
             are stable, and have no evidence of new or enlarging brain metastases, and are not
             using steroids for at least 7 days prior to trial treatment

          -  Has an active autoimmune disease requiring systemic treatment within the past 3 months
             or a documented history of clinically severe autoimmune disease, or a syndrome that
             requires systemic steroids or immunosuppressive agents; subjects with vitiligo or
             resolved childhood asthma/atopy would be an exception to this rule; subjects that
             require intermittent use of bronchodilators or local steroid injections would not be
             excluded from the study; subjects with hypothyroidism stable on hormone replacement or
             Sjogren's syndrome will not be excluded from the study

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

          -  Has an active infection requiring systemic therapy

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

          -  Has received prior therapy with PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or
             anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including
             ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation
             or checkpoint pathways) within 3 months

          -  Has a known history of human immunodeficiency virus (HIV)

          -  Has a known active hepatitis B or hepatitis C

          -  Have received a live vaccine within 30 days prior to the first dose of trial treatment

          -  Is receiving concurrent anti-cancer therapy for metastatic disease
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Rate of disease control
Time Frame:Up to 3 months post-treatment
Safety Issue:
Description:Defined as the percentage of patients either with measurable disease that maintain immune complete response (iCR), immune partial response, immune stable disease (iSD), or with non-measurable disease that achieve iCR or iSD, by 4 months or more in all evaluable patients. A disease control rate of 10% or lower will be considered treatment failure and the regimen will be rejected under this circumstance. A 95% exact binomial confidence interval on disease control rate will be computed. Will also perform secondary analysis on intent-to-treat patient population where those patients who drop out early will be considered as progression.

Secondary Outcome Measures

Measure:Biomarker analyses
Time Frame:Baseline
Safety Issue:
Description:Correlation among biomarkers at baseline in each specimen and between different specimens will be assessed. The association among various continuous and discrete biomarkers or disease status groups will be assessed by the exploratory data analysis using scatter plot matrix, box plots, BLiP plot and trellis plot, etc, and may be tested by t-test/analysis of variance/Wilcoxon rank sun test/Kruskal-Wallis test, whichever is appropriate. Correlation between continuous biomarkers will be examined by Pearson or Spearman rank correlation coefficients.
Measure:Disease control survival
Time Frame:Up to 3 months post-treatment
Safety Issue:
Description:Estimated using Kaplan-Meier method.
Measure:Overall survival time
Time Frame:Up to 3 months post-treatment
Safety Issue:
Description:Estimated using Kaplan-Meier method.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Last Updated

December 7, 2020