Clinical Trials /

Efficacy and Safety of Atezolizumab Plus Capecitabine Adjuvant Therapy for Triple Receptor-Negative Breast Cancer

NCT03756298

Description:

This study will enroll patients who received neoadjuvant therapy for TNBC prior to surgery and did not get pCR. Given the relatively poor prognosis for these patients, this population is considered novel therapeutic as adjuvant treatment. Currently, capecitabine monotherapy could be beneficial to this group of patients according to CREATE-X trial results. The investigators are addressing the effect of anti-PD-L1, atezolizumab combined with capecitabine in patients with TNBC who did not get pCR after neoadjuvant chemotherapy compared to capecitabine monotherapy.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Randomized, Phase II Trial to Evaluate the Efficacy and Safety of Atezolizumab Plus Capecitabine Adjuvant Therapy for Triple Receptor-Negative Breast Cancer With Residual Invasive Cancer After Neoadjuvant Chemotherapy
  • Official Title: Randomized, Phase II Trial to Evaluate the Efficacy and Safety of Atezolizumab Plus Capecitabine Adjuvant Therapy Compared to Capecitabine Monotherapy for Triple Receptor-Negative Breast Cancer With Residual Invasive Cancer After Neoadjuvant Chemotherapy.

Clinical Trial IDs

  • ORG STUDY ID: ATOX-2018
  • NCT ID: NCT03756298

Conditions

  • Triple Negative Breast Cancer

Interventions

DrugSynonymsArms
AtezolizumabCapecitabine1

Purpose

This study will enroll patients who received neoadjuvant therapy for TNBC prior to surgery and did not get pCR. Given the relatively poor prognosis for these patients, this population is considered novel therapeutic as adjuvant treatment. Currently, capecitabine monotherapy could be beneficial to this group of patients according to CREATE-X trial results. We are addressing the effect of anti-PD-L1, atezolizumab combined with capecitabine in patients with TNBC who did not get pCR after neoadjuvant chemotherapy compared to capecitabine monotherapy.

Trial Arms

NameTypeDescriptionInterventions
1Active ComparatorCapecitabine alone arm
  • Atezolizumab
2ExperimentalAtezolizumab + capecitabine combination arm
  • Atezolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  - Male or female ≥ 19 years of age

          -  Patients must have histologically confirmed estrogen receptor (ER)-, progesterone
             receptor (PR)- and HER2-negative (triple-negative) with residual invasive breast
             cancer, as defined by the 2010 and 2013 American Society of Clinical Oncology (ASCO)
             College of American Pathologists (CAP) guidelines (Wolff AC, Hammond MEH), after
             completion of neoadjuvant chemotherapy; residual disease must be ≥ 1 cm in greatest
             dimension, and/or have macroscopically positive lymph nodes (ypN+) observed on
             pathologic exam

          -  Patients must not have metastatic disease (i.e., must be M0)

          -  Patients must have a minimum of 20, available unstained slides from the residual
             (post-neoadjuvant) invasive tumor in primary site or lymph node to be submitted to
             determine PD-L1 expression and other biomarker analysis

          -  Patients must have had neoadjuvant chemotherapy followed by surgery; the recommended
             neoadjuvant treatment should include 16-24 weeks of a third generation chemotherapy
             regimen as recommended by National Comprehensive Cancer Network (NCCN) guidelines for
             triple negative breast cancer. Patients who cannot complete all planned treatment
             cycles for any reason are considered high risk and therefore are eligible for the
             study if they have residual disease

          -  Patients must have completed their final breast surgery with clear resection margins
             for invasive cancer and ductal carcinoma in situ (DCIS) within 90 days prior to
             screening

          -  Patients for whom radiation therapy (RT) to the affected breast or chest wall and
             regional nodal areas is clinically indicated as per NCCN treatment guidelines, should
             receive RT before study treatment; RT administered after registration is also allowed

          -  Patients must have resolution of adverse event(s) of the most recent prior
             chemotherapy and RT to grade 1 or less, except alopecia and ≤ grade 2 neuropathy which
             are allowed

          -  Patients must not have had prior immunotherapy with anti-PD-L1, anti-PD-1, anti-CTLA4
             or similar drugs

          -  Patients must not have had prior capecitabine therapy.

          -  Patients must not have had a history of severe allergic, anaphylactic, or other
             hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins,
             known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster
             ovary cells or any component of the atezolizumab formulation

          -  Patients must have ECOG performance status < 2

          -  Patients must sign and give written informed consent for this protocol in accordance
             with institutional guidelines

          -  Patients should have adequate organ function within 21 days prior to the start of
             study treatment (cycle 1, day1).

               -  Absolute neutrophil count (ANC) ≥ 1500/uL; without granulocyte colony stimulating
                  factor (G-CSF) support within 2 weeks prior to the first study treatment
                  administration

               -  Lymphocyte count ≥ 500/uL

               -  Platelet count ≥ 100,000/uL (without transfusion within 2 weeks prior to the
                  first study treatment administration)

               -  Hemoglobin ≥ 9.0g/dL

               -  AST, ALT, and alkaline phosphatase ≤ 2.5x the upper limit of normal (ULN)

               -  Serum bilirubin ≤ 1.5x ULN, patients with known Gilbert disease who have serum
                  bilirubin ≤ 3.0x ULN may be enrolled.

               -  INR and aPTT ≤ 1.5x ULN, This applies only to patients who are not receiving
                  therapeutic anticoagulation; patients receiving therapeutic anticoagulation
                  should be on a stable dose.

               -  Calculated creatinine clearance ≥ 30mL/min

          -  Women of childbearing potential must have a negative urine or serum pregnancy test
             within 28 day prior to registration; women/men of reproductive potential must have
             agreed to use an effective contraceptive method for the course of the study through
             150 days after the last dose of study medication.

        Exclusion Criteria:

          -  - Patients with evident metastatic lesions at the time of diagnosis

          -  Patients who underwent incomplete surgery for breast cancer

          -  Malignancies other than TNBC within 5 years prior to randomization, with the exception
             of those with well-differentiated thyroid cancer, carcinoma in situ of the cervix or
             basal or squamous cell skin cancer.

          -  Pregnancy or lactation

          -  Evidence of significant uncontrolled concomitant disease that could affect compliance
             with the protocol including significant liver disease, uncontrolled major seizure
             disorder, or uncontrolled psychological disorder.

          -  Significant cardiovascular disease, such as New York Hear Association (NYHA) cardiac
             disease (class II or greater), myocardial infarction within 3 months prior to
             randomization, unstable arrhythmia, or unstable angina.

             : Patients with a known left ventricular ejection fraction (LVEF) <50% will be
             excluded.

          -  Patients who have a history of interstitial pneumonitis that required steroids or
             evidence of active pneumonitis.

          -  Known dihydropyrimidine dehydrogenase (DPD) deficiency or history of severe and
             unexpected reactions to fluoropyrimidine therapy in patients selected to receive
             capecitabine

          -  Hypersensitivity to any component of capecitabine drug formulation in patients
             selected to receive capecitabine.

          -  Patients who have an active infection requiring systemic therapy

          -  Patients who have active autoimmune disease that has required systemic treatment in
             past 2 years (i.e., with use of disease modifying agents, corticosteroids or
             immunosuppressive drugs); patients who are on a stable dose of replacement therapy
             (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for
             adrenal or pituitary insufficiency, etc.) are eligible for this study

          -  Patients who have known active hepatitis B virus (HBV) or hepatitis C virus (HCV)
             infection prior to registration; patients who have completed curative therapy for HCV
             are eligible; patients with known human immunodeficiency virus (HIV) infection are not
             eligible

          -  Patients who have received live vaccines within 30 days prior to registration;
             examples of live vaccines include, but are not limited to, the following: measles,
             mumps, rubella, chicken pox, shingles, yellow fever, rabies, Bacillus Calmette-Guerin
             (BCG), and typhoid (oral) vaccine; seasonal influenza vaccines for injection are
             generally killed virus vaccines and are allowed; however, intranasal influenza
             vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed

          -  Known hypersensitivity to any of excipients of study drugs.

          -  History of severe allergic, anaphylactic, or other hypersensitivity reactions to
             chimeric or humanized antibodies or fusion proteins.

          -  Prior allogenic stem cell or solid organ transplantation

          -  Treatment with systemic immunostimulatory agents (including but not limited to
             interferons or IL-2) within 4 weeks or five half-lives of the drug( whichever is
             shorter) prior to randomization

          -  Treatment with systemic corticosteroids or other systemic immunosuppressive
             medications (including but not limited to prednisone, dexamethasone, cyclophosphamide,
             azathioprine, methotrexate, thalidomide, and anti-TNF agents etc.) within 2 weeks
             prior to randomization

               -  patients who have received acute, low-dose, systemic immunosuppressant
                  medications may be enrolled in the study

               -  The use of inhaled corticosteroids for chronic obstructive pulmonary disease, and
                  low-dose supplemental corticosteroids for adrenocortical insufficiency are
                  allowed.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:19 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:5-yr invasive disease-free survival (IDFS) rate
Time Frame:3 years after last patient enrollment
Safety Issue:
Description:• To compare 5-yr invasive disease-free survival (IDFS) rate of patients with triple-negative breast cancer (TNBC) who had either ≥ 1 cm residual invasive breast cancer and/or positive lymph nodes (> ypN+) after neoadjuvant chemotherapy

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:National Cancer Center, Korea

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