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

NCT03515798 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: PELICAN-IPC 2015-0162016-001868-11
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 12

Brief 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.

Conditions

Inflammatory Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Central evaluation of pathological complete response rate

  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)

  Following completion of neoadjuvant systemic treatment, an average of 24 weeks

• Dose Limiting Toxicity (DLT) rates

  incidence of DLT during the 21 days following the first administration of pembrolizumab in combination with EC, will be assessed separately in the first 3 patients of each stratum (HR+ and HR-). DLTs will be defined according to CTCAE.

  during 21 days following the first administration of pembrolizumab

Secondary Outcomes (8)

• occurrence of serious adverse events and adverse events starting grade 2 or grade 1 (run-in period)

  during 21 days following the first administration of pembrolizumab

• Local evaluation of pathological complete response rate

  Following completion of neoadjuvant systemic treatment, an average of 24 weeks

• Invasive disease-free survival (IDFS)

  3 years

• Invasive disease-free survival (IDFS)

  5 years

• Event free survival (EFS)

  3 years

Other Outcomes (4)

• Evaluation of PD-L1 expression in pre, per and post-treatment tissue

  Following completion of neoadjuvant systemic treatment, an average of 24 weeks

• Measurement of baseline Circulating tumor cells for prospective validation of their prognostic value in IBC

  Following completion of neoadjuvant systemic treatment, an average of 24 weeks

• Disease monitoring

  Following completion of neoadjuvant systemic treatment, an average of 24 weeks

Study Arms (2)

Pembrolizumab

EXPERIMENTAL

EC Paclitaxel + Pembrolizumab Injection

Drug: Pembrolizumab Injection; Drug: neoadjuvant EC-paclitaxel chemotherapy

Standard neoadjuvant chemotherapy

ACTIVE COMPARATOR

EC Paclitaxel alone

Drug: neoadjuvant EC-paclitaxel chemotherapy

Interventions

Pembrolizumab Injection DRUG

Patients will receive intravenously 1 dose of Pembrolizumab every 3 weeks

Also known as: MK3475

Pembrolizumab

neoadjuvant EC-paclitaxel chemotherapy DRUG

The cytotoxic regimen is a combination of dose-dense EC, followed by weekly paclitaxel

Also known as: Epirubicine, Cyclophosphamide, Paclitaxel

Pembrolizumab; Standard neoadjuvant chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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,

You may not qualify if:

• 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.

Sponsors & Collaborators

• Institut Paoli-Calmettes: lead
• MSD France: collaborator
• Oncodistinct: collaborator

Study Sites (12)

Clinique de L'Europe

Amiens, France

Location

Institut Sainte Catherine

Avignon, France

Location

Institut BERGONIE

Bordeaux, France

Location

CENTRE Francois Baclesse

Caen, France

Location

Centre Georges Francois Leclerc

Dijon, 21079, France

Location

Centre Leon Berard

Lyon, France

Location

Institut Curie

Paris, France

Location

Centre Henri Becquerel

Rouen, France

Location

Institut Curie hopital rene huguenin

Saint-Cloud, France

Location

Institut de cancérologie de la loire

Saint-Priest-en-Jarez, France

Location

Centre Paul Strauss

Strasbourg, France

Location

IUCT-Oncopole Institut Claudius Rigaud

Toulouse, France

Location

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Related Links

• Official Website of the sponsor

MeSH Terms

Conditions

Inflammatory Breast Neoplasms

Interventions

pembrolizumab; Epirubicin; Cyclophosphamide; Paclitaxel

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes

Study Officials

• Anthony Goncalves, Pr

  Institut Paoli-Calmettes

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2018
• First Posted: May 4, 2018
• Study Start: August 29, 2018
• Primary Completion: August 22, 2022
• Study Completion (Estimated): August 22, 2027
• Last Updated: September 12, 2025

Record last verified: 2025-09

Locations

FR (12)