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Trial record 13 of 73 for:    inflammatory breast cancer AND Complete Response

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

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ClinicalTrials.gov Identifier: NCT03515798
Recruitment Status : Not yet recruiting
First Posted : May 4, 2018
Last Update Posted : May 4, 2018
Sponsor:
Collaborator:
MSD France
Information provided by (Responsible Party):
Institut Paoli-Calmettes

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.

Condition or disease Intervention/treatment Phase
Inflammatory Breast Cancer Drug: Pembrolizumab Injection Drug: neoadjuvant (F)EC-paclitaxel chemotherapy Phase 2

Detailed 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 (F)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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 81 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Prospective Multicenter Open-label, Randomized Phase II Study of Pembrolizumab in Combination With Neoadjuvant (F)EC-Paclitaxel Regimen in HER2-negative Inflammatory Breast Cancer.
Estimated Study Start Date : June 30, 2018
Estimated Primary Completion Date : December 30, 2020
Estimated Study Completion Date : April 30, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Pembrolizumab
(F)EC Paclitaxel + Pembrolizumab Injection
Drug: Pembrolizumab Injection
Patients will receive intravenously 1 dose of Pembrolizumab every 3 weeks
Other Name: MK3475

Drug: neoadjuvant (F)EC-paclitaxel chemotherapy
The cytotoxic regimen is a combination of FEC (if hormone receptor-positive IBC), followed by weekly paclitaxel or combination of dose-dense EC (if hormone receptor negative i.e. triple-negative IBC), followed by weekly paclitaxel
Other Name: 5-Fluorouracil, Epirubicine, Cyclophosphamide

Active Comparator: Standard neoadjuvant chemotherapy
(F)EC Paclitaxel alone
Drug: neoadjuvant (F)EC-paclitaxel chemotherapy
The cytotoxic regimen is a combination of FEC (if hormone receptor-positive IBC), followed by weekly paclitaxel or combination of dose-dense EC (if hormone receptor negative i.e. triple-negative IBC), followed by weekly paclitaxel
Other Name: 5-Fluorouracil, Epirubicine, Cyclophosphamide




Primary Outcome Measures :
  1. Central evaluation of pathological complete response rate [ Time Frame: Following completion of neoadjuvant systemic treatment, an average of 24 weeks ]
    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)

  2. Dose Limiting Toxicity (DLT) rates [ Time Frame: during 21 days following the first administration of pembrolizumab ]
    incidence of DLT during the 21 days following the first administration of pembrolizumab in combination with FEC/EC, will be assessed separately in the first 6 patients of each stratum (HR+ and HR-). DLTs will be defined according to CTCAE.


Secondary Outcome Measures :
  1. occurrence of serious adverse events and adverse events starting grade 2 or grade 1 (run-in period) [ Time Frame: during 21 days following the first administration of pembrolizumab ]
    according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) V4.03

  2. Local evaluation of pathological complete response rate [ Time Frame: Following completion of neoadjuvant systemic treatment, an average of 24 weeks ]
    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)

  3. Invasive disease-free survival (IDFS) [ Time Frame: 3 years ]
    time from surgery to the first documented occurrence of an event, defined as: Ipsilateral invasive breast tumor recurrence, Ipsilateral local-regional invasive breast cancer recurrence, Distant recurrence, Contralateral invasive breast cancer, Death from any cause

  4. Invasive disease-free survival (IDFS) [ Time Frame: 5 years ]
    time from surgery to the first documented occurrence of an event, defined as: Ipsilateral invasive breast tumor recurrence, Ipsilateral local-regional invasive breast cancer recurrence, Distant recurrence, Contralateral invasive breast cancer, Death from any cause

  5. Event free survival (EFS) [ Time Frame: 3 years ]
    time from randomization to disease progression, disease recurrence (local, regional, distant, or contralateral [invasive or non invasive]), or death from any cause)

  6. Event free survival (EFS) [ Time Frame: 5 years ]
    time from randomization to disease progression, disease recurrence (local, regional, distant, or contralateral [invasive or non invasive]), or death from any cause)

  7. Overall survival (OS) [ Time Frame: 3 years ]
    time from randomization to death from any cause

  8. Overall survival (OS) [ Time Frame: 5 years ]
    time from randomization to death from any cause


Other Outcome Measures:
  1. Evaluation of PD-L1 expression in pre, per and post-treatment tissue [ Time Frame: Following completion of neoadjuvant systemic treatment, an average of 24 weeks ]
    by IHC and mass spectrometry-based proteomics; and in plasma samples using quantitative proteomics,

  2. Measurement of baseline Circulating tumor cells for prospective validation of their prognostic value in IBC [ Time Frame: Following completion of neoadjuvant systemic treatment, an average of 24 weeks ]
    Measurement of baseline CTC for prospective validation of their prognostic value in IBC

  3. Disease monitoring [ Time Frame: Following completion of neoadjuvant systemic treatment, an average of 24 weeks ]
    Purification of ctDNA and specific sequencing for disease monitoring.

  4. Identification of mechanisms of treatment resistance [ Time Frame: Following completion of neoadjuvant systemic treatment, an average of 24 weeks ]
    Immune profiling, NGS and mouse xenografing for ex-vivo phenotypic approaches on post-treatment residual disease in order to identify mechanisms of resistance.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 18 years or older,
  2. Performance status 0 to 2,
  3. Able to comply with the protocol,
  4. Patient affiliated to the national "Social Security" regimen or beneficiary of this regimen,
  5. Patient must have signed a written informed consent form prior to any study specific screening procedures,
  6. Previously untreated, histologically confirmed breast cancer and confirmed inflammatory breast cancer defined as follows:

    - T4d any N following American Joint Committee on Cancer (AJCC)-7th version classification: diffuse Erythema and edema ("peau d'orange") of the breast, occupying at least 1/3 of the breast, with or without underlying palpable mass

  7. HER2 negative tumors by immunohistochemistry (IHC 0 or 1+) or fluorescent/chromogenic in situ hybridization (FISH- or CISH-)
  8. Hormone receptors status known,
  9. No metastases,
  10. Adequate hematologic function: absolute neutrophil count ≥ 1.2 x 109/L AND platelets ≥ 100 x 109 AND Hb ≥ 9 g/dL,
  11. Adequate liver function: total bilirubin ≤ 1.5 ULN unless elevation is due to Gilbert's disease or similar syndrome involving slow conjugation of bilirubin AND - ASAT < 2.5 ULN AND ALAT < 2.5 ULN,
  12. Adequate kidney function: serum creatinine ≤ 1.25 ULN or creatinine clearance ≥ 50 mL/min according to the Cockcroft and Gault formula AND no proteinuria (> 1 g/24 hours),
  13. Adequate cardiac function: left ventricular ejection fraction (LVEF) ≥ 50% (isotopic or ultrasound methods),
  14. International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 ULN AND normal TCA unless subject is receiving anticoagulant therapy, as long as PT or TCA is within therapeutic range of intended use of the anticoagulants,
  15. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of child bearing potential are those who have not been surgically sterilized or have not been free from menses for >1 year. Note: Abstinence is acceptable if this is the established and preferred contraception for the subject,
  16. Female subject of childbearing potential should have a negative urine or serum preg-nancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required,
  17. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.

Exclusion Criteria:

  1. Has metastatic breast cancer,
  2. Has HER2-positive breast cancer,
  3. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment,
  4. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment,
  5. Has a known history of active TB (Bacillus Tuberculosis),
  6. Hypersensitivity to pembrolizumab or any of its excipients,
  7. If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy,
  8. Has a known additional malignancy that progressed or required treatment in the last 5 years, Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer,
  9. 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 (eg. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment,
  10. Has history of/active pneumonitis requiring treatment with steroids or has history of/active interstitial lung disease,
  11. Has an active infection requiring systemic therapy.
  12. 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,
  13. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial,
  14. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment,
  15. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent,
  16. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies),
  17. Has known active Hepatitis B (e.g., HBs Ag reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected),
  18. Has received a live vaccine within 30 days of planned start of study therapy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03515798


Contacts
Contact: Dominique GENRE, MD 33 4 91 22 37 78 drci.up@ipc.unicancer.fr
Contact: Margot Berline 33 4 91 22 37 78 drci.up@ipc.unicancer.fr

Locations
France
Institut Sainte Catherine Not yet recruiting
Avignon, France
Contact: Julien GRENIER, Dr         
Principal Investigator: Julien GRENIER, Dr         
Institut BERGONIE Not yet recruiting
Bordeaux, France
Contact: Camille CHAKIBA-BRUGERE, Dr         
Principal Investigator: Camille CHAKIBA-BRUGERE, Dr         
CENTRE Francois Baclesse Not yet recruiting
Caen, France
Contact: Christelle LEVY, Dr         
Principal Investigator: Christelle LEVY         
Centre Oscar Lambret Not yet recruiting
Lille, France
Contact: Nuria Koteki, Dr         
Principal Investigator: Nuria Koteki, Dr         
Centre Leon Berard Not yet recruiting
Lyon, France
Contact: Thomas BACHELOT, Dr         
Principal Investigator: Thomas BACHELOT, Dr         
Centre Antoine Lacassagne Not yet recruiting
Nice, France
Contact: Jean-Marc FERRERO, Pr         
Principal Investigator: Jean-Marc FERRERO, Pr         
Institut Curie Not yet recruiting
Paris, France
Contact: Jean-Yves PIERGA, Pr         
Principal Investigator: Jean-Yves PIERGA, Pr         
Centre Henri Becquerel Not yet recruiting
Rouen, France
Contact: Marianne LEHEURTEUR, Dr         
Principal Investigator: Marianne LEHEURTEUR, Dr         
Institut Curie hopital rene huguenin Not yet recruiting
Saint-Cloud, France
Contact: Florence Lerebours, Dr         
Principal Investigator: Florence Lerebours         
Institut De Cancérologie de l'Ouest Not yet recruiting
Saint-Herblain, France
Contact: Marie ROBERT, Dr         
Principal Investigator: Marie ROBERT, Dr         
Institut de cancérologie de la loire Not yet recruiting
Saint-Priest-en-Jarez, France
Contact: Jean-Philippe JACQUIN, Pr         
Principal Investigator: Jean-Philippe JACQUIN, Pr         
Centre Paul Strauss Not yet recruiting
Strasbourg, France
Contact: Thierry PETIT, Pr         
Principal Investigator: Thierry PETIT, Pr         
IUCT-Oncopole Institut Claudius Rigaud Not yet recruiting
Toulouse, France
Contact: Florence DALENC, Dr         
Principal Investigator: Florence DALENC, Dr         
Institut Gustave Roussy Not yet recruiting
Villejuif, France
Contact: Suzette Delaloge, Dr         
Principal Investigator: Suzette Delaloge, Dr         
Sponsors and Collaborators
Institut Paoli-Calmettes
MSD France
Investigators
Principal Investigator: Anthony Goncalves, Pr Institut Paoli-Calmettes

Additional Information:
Responsible Party: Institut Paoli-Calmettes
ClinicalTrials.gov Identifier: NCT03515798     History of Changes
Other Study ID Numbers: PELICAN-IPC 2015-016
2016-001868-11 ( EudraCT Number )
First Posted: May 4, 2018    Key Record Dates
Last Update Posted: May 4, 2018
Last Verified: May 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Breast Neoplasms
Inflammatory Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Pembrolizumab
Albumin-Bound Paclitaxel
Cyclophosphamide
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists