ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study Of Changes In PD-L1 Expression During Preoperative Treatment With Nab-Paclitaxel And Pembrolizumab In Hormone Receptor-Positive Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02999477
Recruitment Status : Recruiting
First Posted : December 21, 2016
Last Update Posted : July 25, 2018
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Sara Tolaney, Dana-Farber Cancer Institute

Brief Summary:

This research study is exploring chemotherapy in combination with immunotherapy (a therapy that uses the body's own immune system to control cancer) as a possible treatment for hormone receptor positive breast cancer.

The interventions involved in this study are:

  • Pembrolizumab (MK-3475; Keytruda™)
  • Nab-Paclitaxel (Abraxane

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Pembrolizumab Drug: Nab-Paclitaxel Procedure: Biopsy Phase 1

Detailed Description:

This research study is a Pilot Study, which is the first time investigators are examining this study intervention.

In this research study, the investigators are looking at how the participants body and tumor respond to the combination of Nab-paclitaxel and Pembrolizumab. Also, the investigators will be examining the participants tumor tissue to learn more about the disease.

The FDA (the U.S. Food and Drug Administration) has not approved Pembrolizumab for this specific disease; but it has been approved in the United States for the treatment of other diseases.

The FDA has not approved Nab-paclitaxel as a treatment option for this type of breast cancer; but it has been approved in the United States for the treatment of metastatic breast cancer (breast cancer that has spread to other parts of the body).

Pembrolizumab is a medicine that may treat cancer by working with the participant's immune system. The immune system is the body's natural defense against disease. The immune system sends types of cells called "T cells" throughout the body to detect and fight infections and diseases, including cancer. For some types of cancer, the T cells do not work as they should and are prevented from attacking the tumors. Pembrolizumab is thought to work by blocking a protein in the T cells called PD-1 ("programmed death 1"), which then allows these cells and other parts of the immune system to attack tumors.

Nab-paclitaxel (Abraxane) is part of a class of medications called antimicrotubule agents. It works by stopping the growth and spread of cancer cells by blocking the action of proteins called microtubules.

The combination of Pembrolizumab and Nab-paclitaxel is investigational. "Investigational" means that the combination of study drugs is being studied. The study drugs, when given separately, work in different ways to stop the cancer cells from growing and spreading. However, it is not known if giving the two study drugs at the same time will have a better anti-cancer effect than giving each treatment on its own.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study Of Changes In PD-L1 Expression During Preoperative Treatment With Nab-Paclitaxel And Pembrolizumab In Hormone Receptor-Positive Breast Cancer
Actual Study Start Date : February 23, 2017
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : January 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Nab-Paclitaxel
  • 2 weeks Nab-Paclitaxel Run in
  • Biopsy will be performed
  • Post mono therapy Nab-Paclitaxel administered weekly
  • Post mono therapy Pembrolizumab administered every 3 weeks
  • Agents administered for a total of 15 weeks
Drug: Pembrolizumab
Pembrolizumab will be administered in clinic every three weeks.
Other Name: Keytruda

Drug: Nab-Paclitaxel
Nab-Paclitaxel will be administered in clinic every week.
Other Name: Abraxane

Procedure: Biopsy
Biopsies for research purposes will be performed at three separate timepoints during treatment.

Experimental: Pembrolizumab
  • 2 weeks Pembrolizumab Run in
  • Biopsy will be performed
  • Post mono therapy Nab-Paclitaxel administered weekly
  • Post mono therapy Pembrolizumab administered every 3 weeks
  • Agents administered for a total of 14 weeks
Drug: Pembrolizumab
Pembrolizumab will be administered in clinic every three weeks.
Other Name: Keytruda

Drug: Nab-Paclitaxel
Nab-Paclitaxel will be administered in clinic every week.
Other Name: Abraxane

Procedure: Biopsy
Biopsies for research purposes will be performed at three separate timepoints during treatment.




Primary Outcome Measures :
  1. Change in PD-L1 Expression By Immunohistochemistry From Baseline Biopsy to Biopsy After 2-Week Treatment (biopsy 2) [ Time Frame: 2 weeks ]

Secondary Outcome Measures :
  1. The Absolute Change in PD-L1 Expression By Immunohistochemistry From Baseline Biopsy to Biopsy After Treatment with Nab-Paclitaxel or Pembrolizumab Monotherapy (biopsy 3) [ Time Frame: 2 years ]
  2. The Absolute Change in Expression of Core Immune Biomarkers (stromal TILs; PD-1; PD-L2; CD8) from Baseline Biopsy to Biopsy After 2-Week Treatment (biopsy 2) [ Time Frame: 2 weeks ]
  3. The Absolute Change in Expression of Core Immune Biomarkers (stromal TILs; PD-1; PD-L2; CD8) from Baseline Biopsy to Biopsy After Treatment with Nab-Paclitaxel or Pembrolizumab Monotherapy (biopsy 3) [ Time Frame: 2 years ]
  4. Maximum Grade Of All Treatment-Related Adverse Events [ Time Frame: 2 years ]
  5. Pathologic Complete Response Rate [ Time Frame: 2 years ]
  6. Overall Response Rate [ Time Frame: 2 years ]
  7. Disease-Free Survival [ 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.


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

Inclusion Criteria:

  • Participants must have histologically or cytologically confirmed invasive breast cancer.
  • Participants must have operable breast cancer, with tumors greater than or equal to 2 cm in size; Participants must not have any evidence of metastatic disease.
  • Invasive disease must have been tested for ER, PR, and HER2 and participants must have hormone receptor-positive, HER2-negative breast cancer (ER>1% or PR>1%, AND HER2-negative per ASCO CAP guidelines, 2013).
  • Prior systemic therapy: No prior chemotherapy, biologic therapy, hormonal therapy or investigational therapy for this operable breast cancer.
  • Prior radiation therapy: No prior radiation to the ipsilateral breast.
  • The participant is ≥18 years old
  • The participant has an Eastern Cooperative Oncology Group (ECOG) performance status ≤1 (see Appendix A)
  • Participants must have normal organ and marrow function as defined below:

    • Absolute neutrophil count ≥1500/mm3
    • Platelets ≥100,000/mm3
    • Hemoglobin ≥9 g/dL
    • Total Bilirubin ≤1.5 mg/dL (< 2.0 in participants with known Gilbert's syndrome)
    • Serum creatinine ≤1.5 mg/dL OR calculated GFR ≥60mL/min
    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times the upper limit of normal.
    • International normalized ratio (INR) or Prothrombin Time (PT) <1.5 times the upper limit of normal unless subject is receiving anticoagulant therapy, as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
    • Activated Partial Thromboplastin Time (aPTT) <1.5 times the upper limit of normal unless subject is receiving anticoagulant therapy, as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
  • The participant is capable of understanding and complying with the protocol and has signed the informed consent document.
  • The participant must be willing to undergo the three required research biopsies over the course of protocol therapy. Participants who undergo an attempted research biopsy procedure for the purpose of this protocol, and in whom inadequate tissue is obtained, are not required to undergo a repeat biopsy in order to continue on protocol.
  • The effects of pembrolizumab on the developing human fetus are unknown. For this reason, both women and men of child-bearing potential must agree to use adequate contraception (Section 5.5.2) starting with the first dose of study therapy and for the duration of study participation, through 120 days after the last dose of study medication.

Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. While on the study, women may not breast-feed. Women of childbearing potential are defined as those who have not been surgically sterilized or have not been free from menses for > 1 year.

  • Female subject of childbearing potential should have a negative urine or serum pregnancy test 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.
  • Participants on bisphosphonates may continue receiving bisphosphonate therapy during study treatment.

Exclusion Criteria:

  • The participant has received prior pembrolizumab or any other anti-PD-1, anti-PD-L1, or anti-PD-L2 therapy, or has participated in any prior studies involving pembrolizumab
  • Hypersensitivity to pembrolizumab or any of its excipients.
  • The participant has any history or evidence of active, non-infectious pneumonitis or interstitial lung disease.
  • The participant has an uncontrolled intercurrent illness including, but not limited to, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, congestive heart failure (New York Heart Association Class III or IV; see Appendix B), active ischemic heart disease, myocardial infarction within the previous six months, uncontrolled diabetes mellitus, chronic liver or renal disease, or severe malnutrition.
  • Concurrent use of potent CYP3A4 inhibitors (see Appendix C), such as ketoconazole and erythromycin, should be avoided during the study treatment with nab-paclitaxel.
  • Pregnant women are excluded from this study because pembrolizumab has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with pembrolizumab, breastfeeding should be discontinued if the mother is treated with pembrolizumab.
  • Active infection requiring intravenous antibiotics at week 1 day 1.
  • Individuals with a history of a second malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, and non-melanoma cancer of the skin. Participants with other cancers diagnosed within the past 5 years and felt to be at low risk of recurrence should be discussed with the study sponsor to determine eligibility.
  • The participant has a medical condition that requires chronic systemic steroid therapy or any other form of immunosuppressive medication including disease modifying agents, or has required such therapy in the last 2 years. Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • The participant has an active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents.
  • The participant is positive for Hepatitis B surface antigen, or Hepatitis C RNA.
  • Known HIV-positive participants. HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with pembrolizumab. In addition, these participants are at increased risk of lethal infections with bone marrow suppressive therapy, i.e. nab-paclitaxel. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.
  • The participant has received a live vaccine within 28 days of planned start of study therapy.
  • Seasonal influenza vaccines for infection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (i.e. 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): NCT02999477


Contacts
Contact: Sara Tolaney, MD MPH 617-632-2335 stolaney@partners.org

Locations
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Sara Tolaney, MD MPH    617-632-2335      
Principal Investigator: Sara Tolaney, MD MPH         
Sponsors and Collaborators
Dana-Farber Cancer Institute
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Sara Tolaney, MD MPH Dana-Farber Cancer Institute

Responsible Party: Sara Tolaney, MD, MPH, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT02999477     History of Changes
Other Study ID Numbers: 16-466
First Posted: December 21, 2016    Key Record Dates
Last Update Posted: July 25, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sara Tolaney, Dana-Farber Cancer Institute:
Breast Cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Pembrolizumab
Albumin-Bound Paclitaxel
Hormones
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs