Clinical Trials /

Effect of Bevacizumab in Metastatic Triple Negative Breast Cancer

NCT03577743

Description:

Evaluating efficacy and safety of bevacizumab when combined with chemotherapy (carboplatin and Paclitaxel ) in treatment of patient with metastatic triple negative breast cancer

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Effect of Bevacizumab in Metastatic Triple Negative Breast Cancer
  • Official Title: Phase 2 Study to Evaluate the Effect of Bevacizumab in Metastatic Triple Negative Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: BMTN
  • NCT ID: NCT03577743

Conditions

  • Metastatic Triple Negative Breast Cancer
  • Safety Issues
  • Efficacy

Interventions

DrugSynonymsArms
Bevacizumabavastinexperimental arm

Purpose

Evaluating efficacy and safety of bevacizumab when combined with chemotherapy (carboplatin and Paclitaxel ) in treatment of patient with metastatic triple negative breast cancer

Detailed Description

      Breast cancer is the most common non cutaneous cancer in U.S. women, with an estimated 63,960
      cases of in situ disease and 266,120 cases of invasive disease in 2018.

      Prognosis and selection of therapy may be influenced by the following clinical and pathology
      features (based on conventional histology and immunohistochemistry):

        -  Menopausal status of the patient , Stage of the disease , Grade of the primary tumor
           ,Estrogen receptor (ER) and progesterone receptor (PR) status of the tumor.

        -  Human epidermal growth factor type 2 receptor (HER2/neu) overexpression and/or
           amplification.

        -  Histologic type: Breast cancer is classified into a variety of histologic types, some of
           which have prognostic importance. Favorable histologic types include mucinous,
           medullary, and tubular carcinomas

      The use of molecular profiling in breast cancer includes the following:

        -  ER and PR status testing , HER2/neu receptor status testing.

        -  Gene profile testing by microarray assay or reverse transcription-polymerase chain
           reaction (e.g., MammaPrint, Oncotype DX).

      On the basis of ER, PR, and HER2/neu results, breast cancer is classified as one of the
      following types:

      Hormone receptor positive , HER2/neu positive and Triple negative (ER, PR, and HER2/neu
      negative).

      ER, PR, and HER2 status are important in determining prognosis and in predicting response to
      endocrine and HER2-directed therapy.

      Metastatic Triple-negative breast cancer (TNBC) is a diagnosis of exclusion, defined by the
      lack of expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal
      growth factor receptor 2 (HER2) .

      TNBC tends to occur in younger, often premenopausal patients, African Americans, and in
      association with hereditary syndromes, most commonly germline BRCA1 mutations.

      It constitutes up to 15% of all breast cancers but accounts for > 25% of breast
      cancer-related deaths as it has an inherent predisposition for rapid dissemination and
      visceral metastases with limited improvements in overall survival and inferior clinical
      outcomes It is characterized by higher incidence of brain metastases and rapid progression
      from the onset of metastasis to death Having aggressive biology more than other breast types
      due to high risk of early relapse between the first and third years after diagnosis ,
      metastases are rarely preceded by local recurrence and most deaths occur in the first 5 years
      Based on 3,247 gene expression profiles from 21 breast cancer data sets, we discovered six
      TNBC subtypes including 2 basal-like (BL1 and BL2), an immunomodulatory (IM), a mesenchymal
      (M), a mesenchymal stem-like (MSL), and a luminal androgen receptor (LAR) subtype.

      Due to the palliative intent of treatment as in MBC it is critical that an individualized
      approach is taken that incorporates patient, disease, and treatment-related factors,
      including an individual oncologist treatment preference.

      Emerging clinical trials of targeted agents offer glimpses of hope, including the use of poly
      ADP ribose polymerase inhibitors(PARP I) in TNBCs with DNA repair defects, antiandrogen
      therapy in patients who are androgen receptor positive, and phosphatidylinositol 3-kinase
      inhibitors (PI3K) which may sensitize BRCA-proficient TNBCs to poly ADP ribose polymerase
      inhibition Moreover, a subset of TNBCs seems to be immunogenic, with high levels of
      tumor-infiltrating lymphocytes, providing a strong rationale for ongoing efforts to explore
      the role of immunotherapies.

      There have been several head-to-head chemotherapy trials performed within the metastatic
      setting, and much of what is applied in clinical practice is extrapolated from chemotherapy
      trials in the adjuvant setting, with taxanes and anthracyclines incorporated early on in the
      patient's treatment course.

      Angiogenesis is essential for the development of malignancies and plays a central role in the
      early stages of growth, invasion, and metastatic spread of breast cancer (BC), thus
      representing a reasonable therapeutic target. This evidence is a solid biological rationale
      for the use of therapeutic agents able to interfere with the VEGF (vaso endothelial growth
      factor ) function.

      The recombinant monoclonal antibody bevacizumab is currently the most widely used and
      developed antiangiogenic drug in the treatment of breast cancer(BC) , able to recognize all
      the isoforms of VEGFA, preventing its binding to the cellular receptor, and inhibiting the
      angiogenic and proliferative signal. In vivo studies showed that bevacizumab inhibits both
      proliferation and migration of endothelial cells induced by VEGFA; besides in some models of
      human BC, the treatment with bevacizumab was associated to a reduction in microvascular
      density According to the Folkman model, bevacizumab would lead to the normalization of the
      tumor vasculature, resulting in a restoration of cancer cells susceptibility to chemotherapy.
      This theory is currently accompanied by the newer "action and reaction" model.

      The humanized, anti-VEGF monoclonal antibody bevacizumab has been shown to increase
      progression-free survival (PFS) and/ or overall survival (OS) in metastatic breast cancer
      (MBC), response rate RR .

      Taxanes as part of chemotherapy have been studied as having an inhibitory action on the
      proliferation of endothelial progenitor cells, with an antiangiogenic effect at lower doses
      than those needed to inhibit the proliferation of cancer cells. The resulting hypoxia induces
      cancer cells to a kind of "reaction" through the autocrine production of proangiogenic agents
      several evidences of their benefits on clinical outcomes, such as OS, time to progression
      (TTP), and over all response rate ( ORR.) Even if conventional taxanes demonstrated to be
      more active in endocrine receptor-negative tumors and are indicated in the first-line
      treatment of TNBC
    

Trial Arms

NameTypeDescriptionInterventions
experimental armExperimentalbevacizumab and chemotherapy given every 21 day untill disease progression or unacceptable toxicity
  • Bevacizumab

Eligibility Criteria

        Inclusion Criteria:

          1. Female patient firstly diagnosed with metastatic TNBC or after adjuvant treatment OF
             TNBC by immune histochemistry and biopsy

          2. Age >18 Y

          3. Performance status (PS ) 0-2

          4. Did not have any bleeding disorders.

          5. Receive only one line of chemotherapy in adjuvant ttt

        Exclusion Criteria:

          1. Male patient

          2. PS >2

          3. Uncontrolled HPTN

          4. Have history of bleeding disorders

          5. Receive > one line of chemotherapy

          6. Have other type of malignancy
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:Accepts Healthy Volunteers

Primary Outcome Measures

Measure:- progression free survival
Time Frame:after six month from last enrollment
Safety Issue:
Description:the length of time during and after the treatment that a patient lives with the disease but it does not get worse

Secondary Outcome Measures

Measure:- Response rate (R.R) :
Time Frame:after 1 year from enrollment
Safety Issue:
Description:length of time from the date of diagnosis to the time of death or lost follow up.
Measure:- Over all survival.
Time Frame:after 3 years
Safety Issue:
Description:the length of time from either the date of diagnosis or the start of treatment for a disease, such as cancer, that patients diagnosed with the disease are still alive.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Assiut University

Trial Keywords

  • antiangiogenesis
  • taxanes and carboplatin
  • metastatic TNBC

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