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Trial record 6 of 61 for:    PD-1 and breast cancer | Recruiting, Not yet recruiting, Available Studies

Effect of Pembrolizumab (Keytruda®) on Biomarkers in Early ER/PR Negative Breast Cancer.

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ClinicalTrials.gov Identifier: NCT03197389
Recruitment Status : Recruiting
First Posted : June 23, 2017
Last Update Posted : October 11, 2018
Sponsor:
Information provided by (Responsible Party):
Universitaire Ziekenhuizen Leuven

Brief Summary:

The study consists of 2 parts: a retrospective study, and a prospective clinical study with pembrolizumab (Keytruda®) (Phase 0).

  1. Retrospective study (S58910):

    This is a retrospective analysis to study the expression of PD-L1 in ER/PR negative breast tumors and to correlate this PD-L1 expression with tumor infiltrating lymphocytes (TILs), proliferation, expression of apoptosis and clinical outcome (development of distant metastases).

  2. Phase 0 study:

This is a Phase 0 single center, open-label, non-randomized, study in patients with early ER/PR negative breast cancer. Patients will be treated with one injection of Pembrolizumab (Keytruda®) administered intravenously at 200 mg 10 +/- 4 days before surgery. This phase 0 study will consist of 2 cohorts; cohort A will include patients who are scheduled for upfront surgery. Cohort A1 will include patients with Her2 negative tumors and Cohort A2 patients with Her2 positive tumors. Cohort B will include patients who received neoadjuvant chemotherapy (with anti-Her2 therapy if Her2 positive) and who have clear signs of residual tumor on imaging after finishing neoadjuvant chemotherapy (i.e. on imaging estimated residual tumor size of at least 10 mm). Cohort B1 will include Her2 negative tumors and Cohort B2 Her2 positive tumors. The injection will be given in the oncological outpatient unit. Patients will be monitored carefully for the development of adverse experiences/events. Adverse experiences/events will be evaluated according to criteria outlined in the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.0.


Condition or disease Intervention/treatment Phase
Breast Cancer Triple Negative Breast Cancer Hormone Receptor Negative Neoplasm Drug: Pembrolizumab Early Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 34 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Effect of Pembrolizumab (Keytruda®) on Biomarkers Related to Intratumoral Immunity, Proliferation and Apoptosis in Early ER/PR Negative Breast Cancer.
Actual Study Start Date : January 18, 2018
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Cohort A1
Cohort A1 will include patients with a triple negative breast tumor. Patients will be treated with one injection of Pembrolizumab (Keytruda®) administered intravenously at 200 mg 10 +/- 4 days before surgery.
Drug: Pembrolizumab
Biological: humanized anti-PD-1 monoclonal antibody humanized anti-PD-1 monoclonal antibody is a programmed death-1 (PD-1) immune checkpoint inhibitor antibody, which selectively interferes with the combination of PD-1 with its ligands, PD-L1 and PD-L2.
Other Name: Keytruda

Cohort A2
Cohort A2 will include patients with ER/PR negative and Her2 positive breast tumor. Patients will be treated with one injection of Pembrolizumab (Keytruda®) administered intravenously at 200 mg 10 +/- 4 days before surgery.
Drug: Pembrolizumab
Biological: humanized anti-PD-1 monoclonal antibody humanized anti-PD-1 monoclonal antibody is a programmed death-1 (PD-1) immune checkpoint inhibitor antibody, which selectively interferes with the combination of PD-1 with its ligands, PD-L1 and PD-L2.
Other Name: Keytruda

Cohort B1
Cohort B1 will include patients with a triple negative breast tumor who received neoadjuvant chemotherapy and who have clear signs of residual tumor on imaging after finishing neoadjuvant chemotherapy (i.e. on imaging estimated residual tumor size of at least 10 mm). Patients will be treated with one injection of Pembrolizumab (Keytruda®) administered intravenously at 200 mg 10 +/- 4 days before surgery.
Drug: Pembrolizumab
Biological: humanized anti-PD-1 monoclonal antibody humanized anti-PD-1 monoclonal antibody is a programmed death-1 (PD-1) immune checkpoint inhibitor antibody, which selectively interferes with the combination of PD-1 with its ligands, PD-L1 and PD-L2.
Other Name: Keytruda

Cohort B2
Cohort B2 will include patients with a ER/PR negative and Her2 positive breast tumor who received neoadjuvant chemotherapy and who have clear signs of residual tumor on imaging after finishing neoadjuvant chemotherapy (i.e. on imaging estimated residual tumor size of at least 10 mm). Patients will be treated with one injection of Pembrolizumab (Keytruda®) administered intravenously at 200 mg 10 +/- 4 days before surgery.
Drug: Pembrolizumab
Biological: humanized anti-PD-1 monoclonal antibody humanized anti-PD-1 monoclonal antibody is a programmed death-1 (PD-1) immune checkpoint inhibitor antibody, which selectively interferes with the combination of PD-1 with its ligands, PD-L1 and PD-L2.
Other Name: Keytruda




Primary Outcome Measures :
  1. PD-1 expression [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. Increase in the amount of TILs [ Time Frame: 2 years ]
  2. PD-L1 expression [ Time Frame: 2 years ]

Other Outcome Measures:
  1. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 2 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Be willing and able to provide written informed consent/assent for the trial.
  2. Be 18 years of age on day of signing informed consent.
  3. Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion if needed. Newly obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 0. Subjects for whom newly obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Sponsor.
  4. Have a performance status of 0 or 1 on the ECOG Performance Scale.
  5. Have non-metastatic operable newly diagnosed primary invasive carcinoma of the breast that is:

    1. Histologically confirmed
    2. ER/PR negative. ER/PR status will be evaluated with Allred score (semi-quantitative measurement) following ASCO CAP guidelines 2009.
    3. HER2 negative of positive. HER2 status will be evaluated using IHC followed by FISH with dual probe (ASCO CAP guidelines 2013).
    4. Primary tumor size greater than 1 cm, measured by any of clinical examination, mammography, ultrasound or magnetic resonance imaging
    5. Any clinical nodal status
  6. Have evaluable core biopsy for IHC
  7. Be willing to provide plasma/blood samples
  8. After neo-adjuvant chemotherapy (cohort B1 and B2) patients must have residual tumor >1cm and must be willing to provide evaluable new tumor biopsy for IHC
  9. Demonstrate adequate organ function, all screening labs should be performed within 14 days of treatment initiation.
  10. Female subject of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  11. Female subjects of childbearing potential (Section 5.7.2) must be willing to use an adequate method of contraception as outlined in Section 5.7.2 - Contraception, for the course of the study through 120 days after receiving the study medication.

    Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

  12. Male subjects of childbearing potential (Section 5.7.1) must agree to use an adequate method of contraception as outlined in Section 5.7.1- Contraception, until 120 after receiving the study therapy.

Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

Exclusion Criteria:

  1. 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 receiving the treatment dose.
  2. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to receiving the trial treatment.
  3. Has a known history of active TB (Bacillus Tuberculosis)
  4. Hypersensitivity to pembrolizumab or any of its excipients.
  5. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
  6. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 0 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.

    • Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
    • Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
  7. Has a known additional malignancy that is progressing or requires active treatment. 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.
  8. 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.
  9. Has known history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
  10. Has an active infection requiring systemic therapy.
  11. 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.
  12. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  13. 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.
  14. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 agent or co-inhibitory T-cell receptor therapy (e.g. OX40-CD137, CTLA-4)
  15. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  16. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  17. Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.

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): NCT03197389


Contacts
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Contact: Ann Smeets, Prof. Dr. +32 16346832 secretariaat.oncologischeheelkunde@uzleuven.be
Contact: Hanne Vos, MSc +32 16340903 hanne.vos@uzleuven.be

Locations
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Belgium
University Hospitals Leuven Recruiting
Leuven, Belgium, 3000
Contact: Ann Smeets, Prof. Dr.    +32 16346832    secretariaat.oncologischeheelkunde@uzleuven.be   
Contact    +32 16340903    hanne.vos@uzleuven.be   
Sponsors and Collaborators
Universitaire Ziekenhuizen Leuven
Investigators
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Principal Investigator: Ann Smeets, Prof. Dr. University Hospitals Leuven

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Responsible Party: Universitaire Ziekenhuizen Leuven
ClinicalTrials.gov Identifier: NCT03197389     History of Changes
Other Study ID Numbers: MK 3475-318
First Posted: June 23, 2017    Key Record Dates
Last Update Posted: October 11, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Keywords provided by Universitaire Ziekenhuizen Leuven:
Biomarker

Additional relevant MeSH terms:
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Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents