PEMBROLIZUMAB for Breast cancer|Inflammatory breast cancer|HER2-negative breast cancer

Inclusion criteria

• {"criterion_text":"-Male/female participants who are at least 18 years of age on the day of signing informed consent"}
• {"criterion_text":"-Have adequate organ function. Specimens must be collected within 10 days prior to the start of study treatment"}
• {"criterion_text":"-Adequate hematologic function: absolute neutrophil count ≥ 1.5 x 109/L AND platelets ≥ 100 x 109 AND Hb ≥ 9.0 g/dL or ≥5.6 mmol/L, Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks"}
• {"criterion_text":"-Adequate liver function: total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN AND - ASAT ≤ 2.5 ULN AND ALAT ≤ 2.5 ULN"}
• {"criterion_text":"-Adequate kidney function: serum creatinine ≤ 1.5 ULN or creatinine clearance ≥ 30 mL/min for participant with creatinine levels >1.5 × institutional ULN, Creatinine clear-ance (CrCl) should be calculated per institutional standard"}
• {"criterion_text":"-International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 ULN unless subject is receiving anticoagulant therapy, as long as PT or TCA is within therapeutic range of in-tended use of the anticoagulants"}
• {"criterion_text":"-Adequate cardiac function: left ventricular ejection fraction (LVEF) ≥ 50% (isotopic or ul-trasound methods)"}
• {"criterion_text":"-A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies: a.) Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR b.) A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 12 months after the last dose of cyclophosphamide and 4 months after the last dose of pembrolizumab, whichever come last. Note: Abstinence is acceptable if this is the established and preferred contraception for the subject"}
• {"criterion_text":"-A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 6 months after the last dose of study treatment and refrain from donating sperm during this period (corresponding to time needed to eliminate any study treatments plus an additional 120 days (a spermatogenesis cycle) for study treatments with risk of genotoxicity at any dose)"}
• {"criterion_text":"-Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1"}
• {"criterion_text":"-Able to comply with the protocol"}
• {"criterion_text":"-Patient affiliated to the national “Social Security” regimen or beneficiary of this regimen, or any other regimen of social security"}
• {"criterion_text":"-Patient (or legally acceptable representative if applicable) has provided written informed consent for the trial"}
• {"criterion_text":"-Previously untreated, histologically confirmed diagnosis of breast cancer and confirmed inflammatory breast cancer defined as follows: - T4d any N following American Joint Committee on Cancer (AJCC)-8th ver-sion classification: breast erythema, edema and/or peau d'orange, occupying at least 1/3 of the breast, with or without underlying palpable mass, duration of history of no more than 6 months"}
• {"criterion_text":"-HER2 negative tumors by immunohistochemistry (IHC 0 or 1+) or fluores-cent/chromogenic in situ hybridization (FISH- or CISH-)"}
• {"criterion_text":"-Hormone receptors status known"}
• {"criterion_text":"-No metastases"}

Exclusion criteria

• {"criterion_text":"-Has metastatic breast cancer"}
• {"criterion_text":"-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)"}
• {"criterion_text":"-Has HER2-positive breast cancer"}
• {"criterion_text":"-Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)"}
• {"criterion_text":"-Has known history of Hepatitis B (e.g., HBsAg reactive) or known active Hepatitis C virus infection (e.g., HCV RNA [qualitative] is detected)"}
• {"criterion_text":"-Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vac-cines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live at-tenuated vaccines and are not allowed"}
• {"criterion_text":"-Has bilateral breast cancer"}
• {"criterion_text":"-Prior allogeneic stem cell or solid organ transplantation"}
• {"criterion_text":"-A WOCBP who has a positive serum pregnancy test within 72 hours prior to randomiza-tion"}
• {"criterion_text":"-Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment"}
• {"criterion_text":"-Has known active CNS disease or carcinomatous meningitis"}
• {"criterion_text":"-Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients"}
• {"criterion_text":"-Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppres-sive therapy within 7 days prior to the first dose of study drug"}
• {"criterion_text":"-Has a known history of active TB (Bacillus Tuberculosis)"}
• {"criterion_text":"-If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy"}
• {"criterion_text":"-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"}
• {"criterion_text":"-Has a history of (non-infectious) pneumonitis that required steroids or has current pneu-monitis"}
• {"criterion_text":"-Has an active infection requiring systemic therapy"}
• {"criterion_text":"-Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator"}
• {"criterion_text":"-Has known psychiatric or substance abuse disorders that would interfere with coopera-tion with the requirements of the trial"}
• {"criterion_text":"-Is pregnant or breastfeeding, or expecting to conceive or father children within the pro-jected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment"}

Primary endpoints

• {"endpoint_text":"-Central evaluation of pathological complete response rate as defined as absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes following completion of NAST (i.e., ypT0/is, ypN0 in the current AJCC staging system)","definition_or_measurement_approach":"Central histopathology evaluation of resected breast specimen and all sampled ipsilateral lymph nodes; absence of residual invasive cancer (ypT0/is, ypN0 according to AJCC staging) following completion of neoadjuvant systemic therapy"}
• {"endpoint_text":"-Dose Limiting Toxicity (DLT) rates as defined as incidence of DLT during the 21 days following the first administration of pembrolizumab in combination with EC, will be assessed in the first 6 patients","definition_or_measurement_approach":"Incidence of DLT during the 21 days following first administration of pembrolizumab plus EC; assessed in the first 6 patients (safety run-in)"}

Secondary endpoints

• {"endpoint_text":"-Occurrence of serious adverse events and adverse events starting grade 2 or grade 1 (run-in period) according to the National Cancer Institute (NCI) Common Terminology Criteria for Ad-verse Events (CTCAE) V5.0","definition_or_measurement_approach":"Assessment of adverse events and serious adverse events graded per NCI CTCAE v5.0; includes early grade 1/2 events during run-in"}
• {"endpoint_text":"-Local evaluation of pathological complete response rate as defined as absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes following completion of NAST (i.e., ypT0/is, ypN0 in the current AJCC staging system)","definition_or_measurement_approach":"Local (site) histopathology evaluation using H&E of resected breast specimen and sampled lymph nodes; absence of invasive cancer (ypT0/is, ypN0)"}
• {"endpoint_text":"-Invasive disease-free survival (IDFS), as defined as time from surgery to the first documented occurrence of an event, defined as: Ipsilateral invasive breast tumor recurrence or\tIpsilateral local-regional invasive breast cancer recurrence or Distant recurrence or contralateral invasive breast cancer or death from any cause","definition_or_measurement_approach":"Time-to-event endpoint measured from surgery to first documented qualifying event (local, regional, distant recurrence, contralateral invasive breast cancer, or death)"}
• {"endpoint_text":"-Event free survival (EFS), defined as time from randomization to disease progression, disease recurrence (local, regional, distant, or contralateral [invasive or non-invasive]), or death from any cause)","definition_or_measurement_approach":"Time from randomization to disease progression, recurrence (local/regional/distant/contralateral invasive or non-invasive), or death"}
• {"endpoint_text":"-Overall survival (OS), defined as time from randomization to death from any cause","definition_or_measurement_approach":"Time from randomization to death from any cause"}

France

Earliest CTIS Part Ii Submission Date

04-09-2024

Latest Decision Or Authorization Date

31-10-2024

Processing Time Days

57

Number Of Sites

13

Number Of Participants

72

Primary sponsor

Full Name

Institut Paoli Calmettes

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France