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Active Clinical Trials

Pembrolizumab in Treating Patients With Triple-Negative Breast Cancer

Active NCT:
02954874
Wexford Health + Wellness Pavilion, Jefferson Hospital
Wexford Health + Wellness Pavilion, Jefferson Hospital

Allegheny General Hospital
Allegheny General Hospital

Forbes Hospital
Forbes Hospital

Jefferson Hospital
Jefferson Hospital

Saint Vincent Hospital
Saint Vincent Hospital

West Penn Hospital
West Penn Hospital

Category:
Cancer - Breast
Sponsor: 
National Cancer Institute (NCI)
Contact: 

For more information, please contact Samantha Cavolo at 412-359-6449 or Samantha.Cavolo@ahn.org

S1418/BR006: A Randomized Phase III Trial to Evaluate the Efficacy and Safety of MK-3475 (Pembrolizumab) as Adjuvant Therapy for Triple Receptor-Negative Breast Cancer with = 1 cm Residual Invasive Cancer or Positive Lymph Nodes (ypN+) After Neoadjuvant Chemotherapy

Purpose: 

This randomized phase III trial studies how well pembrolizumab works in treating triple-negative breast cancer. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread.
 

Inclusion Criteria:

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

    • NOTE: Immunohistochemistry (IHC)-positive isolated tumor cells in the lymph node (N0 [i+]) are not considered node-positive and these patients also must have >= 1 cm residual invasive cancer in the breast in order to be eligible
  • Patients must not have metastatic disease (i.e., must be M0)
  • It is preferred that axillary lymph node sampling is performed after completion of neoadjuvant chemotherapy to allow more accurate assessment of pathologic response; patients must have a complete axillary lymph node dissection after neoadjuvant chemotherapy in the following situations (exceptions will be granted for patients participating in the Alliance A11202 trial):

    • Patients had documented pathologic involvement of the axillary nodes (fine needle aspiration [FNA] or core biopsy) before neoadjuvant chemotherapy and had sentinel node biopsy after neoadjuvant chemotherapy with positive sentinel node(s)
    • Patient had documented pathologic involvement of the axillary nodes (FNA or core biopsy) before neoadjuvant chemotherapy and had only 1 sentinel lymph node removed after neoadjuvant chemotherapy

      • NOTE: Patients who undergo sentinel node biopsy before starting neoadjuvant treatment and do not undergo post neoadjuvant assessment of the axillary nodes or who have negative axillary nodes on post neoadjuvant assessment must have >= 1 cm residual invasive cancer in the breast after completion of neoadjuvant chemotherapy
  • Patients must have a minimum of five, available unstained slides from the residual (post-neoadjuvant) invasive tumor in primary site or lymph node to be submitted within 7 days after registration to determine PD-L1 expression; the tumor tissue must be adequate for PD-L1 testing, which typically requires a minimum of 100 cancer cells per slide
  • Patients must be offered the opportunity to participate in specimen banking
  • 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 (examples include dose dense adriamycin-cytoxan [AC] followed by dose-dense paclitaxel; weekly paclitaxel x 12 followed or preceded by cyclophosphamide-adriamycin-fluorouracil [FAC], fluorouracil-epirubicin-cytoxan [FEC], AC or dose dense AC; docetaxel either followed or preceded by FEC/FAC or AC; carboplatin-containing neoadjuvant chemotherapy is also allowed); 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 resolution of adverse event(s) of the most recent prior chemotherapy to grade 1 or less, except alopecia and =< grade 2 neuropathy which are allowed
  • Patients may receive post-operative (adjuvant) chemotherapy for up to 24 weeks of duration (e.g. 8 cycles of capecitabine as in the CREATE-X trial) after completion of surgery at the discretion of the treating physician; patients must have resolution of adverse event(s) of the most recent prior chemotherapy to grade 1 or less, except alopecia and =< grade 2 neuropathy which are allowed; adjuvant chemotherapy, if administered, must have been completed within 35 days prior to screening registration and must be given prior to radiation
  • Patients must have completed their final breast surgery (rendering them free from disease) with clear resection margins for invasive cancer and ductal carcinoma in situ (DCIS) within 90 days prior to screening registration for patients not receiving post-operative (adjuvant) chemotherapy, or within 210 days prior to screening registration for patients who have completed post-operative (adjuvant) chemotherapy; positive margins are allowed only if the surgical team of the patient deems further resection impossible
  • 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 after randomization when possible, concomitant with MK-3475 (pembrolizumab) if randomized to the experimental arm; however, RT administered prior to registration is also allowed; patients must specify at the time of screening registration whether or not they will receive RT and the extent of intended RT
  • Patients must not have had prior immunotherapy with anti-PD-L1, anti-PD-1, anti-CTLA4 or similar drugs; patients must not be planning to receive any of the prohibited therapies during the screening or treatment phases of the study
  • Patients must not be planning to receive concomitantly other biologic therapy, hormonal therapy, other chemotherapy, surgery or other anti-cancer therapy except radiation therapy while receiving treatment on this protocol
  • Patients must have Zubrod performance status =< 2
  • Patients must not have a history of (non-infectious) pneumonitis that required steroids or evidence of active pneumonitis
  • Patients must not have an active infection requiring systemic therapy
  • Patients must not 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); 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
  • Patients must not 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
  • Patients must not 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 eligible if they meet each of the following 3 criteria:

    • CD4 counts >= 350 mm^3
    • Serum HIV viral load of < 25,000 IU/ml and
    • Treated on a stable antiretroviral regimen
  • No other prior invasive malignancy is allowed except for the following: adequately treated basal (or squamous cell) skin cancer, in situ breast or cervical cancer; stage I or II invasive cancer treated with a curative intent without evidence of disease recurrence for at least five years
  • Patients must be informed of the investigational nature of this study and must sign and give written informed consent for this protocol in accordance with institutional and federal guidelines
  • As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
  • STEP 2 REGISTRATION
  • Patients must not be registered to step 2 until receiving confirmation from the Southwest Oncology Group (SWOG) Statistical Center that the patient's tissue specimen was adequate for PD-L1 testing; patients must be registered within 7 days of receiving the e-mail notification confirming submission was evaluable for PD-L1 status
  • A serum thyroid-stimulating hormone (TSH) must be obtained within 28 days prior to step 2 registration to obtain a baseline value
  • Absolute neutrophil count (ANC) >= 1,500 microliter (mcL)
  • Platelets >= 100,000/mcL
  • Hemoglobin >= 9 g/dL
  • Total bilirubin =< 1.5 x institutional upper limit of normal (IULN) (except Gilbert's syndrome, who must have a total bilirubin < 3.0 mg/dL)
  • Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2.5 x IULN
  • Alkaline phosphatase =< 2.5 x IULN
  • Serum creatinine =< IULN OR measured or calculated creatinine clearance >= 60 mL/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 120 days after the last dose of study medication; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy, bilateral tubal ligation, or vasectomy; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures; patients must not be pregnant or nursing
  • Site must verify that there is no known change in the step 1 eligibility since initial registration
Eligibility Criteria: 
Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No