Study of Immunotherapy in Combination With Chemotherapy in HER2-negative Inflammatory Breast Cancer

  • STATUS
    Recruiting
  • End date
    Apr 30, 2025
  • participants needed
    81
  • sponsor
    Institut Paoli-Calmettes
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Updated on 25 January 2021
See if I qualify
paclitaxel
edema
erythema
cyclophosphamide
ejection fraction
metastasis
neutrophil count
immunohistochemistry
HER2
erbb2
cish
inflammatory breast cancer
chromogenic in situ hybridization
peau d'orange

Summary

This phase II multicentre randomized open-label study will assess the safety and efficacy of Pembrolizumab in combination with standard chemotherapy in inflammatory breast cancer. Pembrolizumab will be administered every 3 weeks during the neoadjuvant chemotherapy. Tissue and blood samples will be collected pre- and post-treatment for translational research.

Description

Inflammatory breast cancer (IBC) is a rare and highly aggressive subtype of locally advanced breast cancer representing approximately 5% of all breast cancers that requires immediate aggressive treatment. Significant progress has been made in recent years using a combination of treatments, including neoadjuvant chemotherapy, surgery and radiation therapy.

Accumulating data indicate a prognostic and/or predictive impact for immune-response variables in BC. Recent data, suggest that PD-L1 is overexpressed in a significant number of BC, notably in IBC and may have significant prognostic or predictive value. Furthermore it may be targeted to restore or boost functional antitumor immunity. Pembrolizumab, a PD-1-directed monoclonal antibody is already registered and has an out-standing activity in advanced melanoma and NSCLC patients, with promising results in several other tumor types, including triple-negative BC, and a favorable profile of tolerance.

Thus, potential benefits of pembrolizumab in combination with a conventional cytotoxic backbone may be considered as high in HER2-negative IBC.

The aim of the study is to assess the pathological complete response rate following neoadjuvant EC-paclitaxel chemotherapy plus pembrolizumab and to assess if neoadjuvant chemotherapy with anthracycline-based induction in combination with pembrolizumab exposes IBC patients to significant toxicity. rates.

Details
Condition Breast Cancer, Inflammatory Breast Cancer, inflammatory breast cancers
Treatment Pembrolizumab Injection, neoadjuvant (F)EC-paclitaxel chemotherapy, neoadjuvant EC-paclitaxel chemotherapy
Clinical Study IdentifierNCT03515798
SponsorInstitut Paoli-Calmettes
Last Modified on25 January 2021

Eligibility

 Yes No Not Sure

Inclusion Criteria

Is your age greater than or equal to 18 yrs?
Gender: Male or Female
Do you have any of these conditions: Inflammatory Breast Cancer or Breast Cancer?
Do you have any of these conditions: Inflammatory Breast Cancer or Breast Cancer or inflammatory breast cancers?
Male/female participants who are at least 18 years of age on the day of signing informed consent
Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 Evaluation of ECOG is to be performed within 7 days prior to the date of randomization. Note: may consider ECOG PS 2 if good rationale provided and discussed with Sponsor team
Able to comply with the protocol
Patient affiliated to the national "Social Security" regimen or beneficiary of this regimen, or any other regimen of social security
Patient (or legally acceptable representative if applicable) has provided written informed consent for the trial
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 version 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
HER2 negative tumors by immunohistochemistry (IHC 0 or 1+) or fluorescent/chromogenic in situ hybridization (FISH- or CISH-)
Hormone receptors status known
No metastases
Have adequate organ function. Specimens must be collected within 10 days prior to the start of study treatment
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
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
Adequate kidney function: serum creatinine 1.5 ULN or creatinine clearance 30 mL/min for participant with creatinine levels >1.5 institutional ULN, Creatinine clearance (CrCl) should be calculated per institutional standard
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 intended use of the anticoagulants
Adequate cardiac function: left ventricular ejection fraction (LVEF) 50% (isotopic or ultrasound methods)
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
Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR
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
\. 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)

Exclusion Criteria

Has metastatic breast cancer
Has HER2-positive breast cancer
Has bilateral breast cancer
Prior allogeneic stem cell or solid organ transplantation
A WOCBP who has a positive serum pregnancy test within 72 hours prior to randomiza-tion
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, Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent
Has known active CNS disease or carcinomatous meningitis
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 immunosuppressive therapy within 7 days prior to the first dose of study drug
Has a known history of active TB (Bacillus Tuberculosis)
Has severe hypersensitivity (Grade 3) to pembrolizumab and/or any of its excipients
If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded
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
Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
Has an active infection requiring systemic therapy
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
Has known psychiatric or substance abuse disorders that would interfere with coopera-tion with the requirements of the trial
Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment
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)
Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
Has known history of Hepatitis B (e.g., HBsAg reactive) or known active Hepatitis C virus infection (e.g., HCV RNA [qualitative] is detected)
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-Gurin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed
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paclitaxel
edema
erythema
cyclophosphamide
ejection fraction
metastasis
neutrophil count
immunohistochemistry
HER2
erbb2
cish
inflammatory breast cancer
chromogenic in situ hybridization
peau d'orange

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