A Study of Pembrolizumab With Carboplatin and Gemcitabine in Patients With Metastatic Triple Negative Breast Cancer

NCT02755272 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: BR-07616-1013
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 6

Brief Summary

The main purpose of this study is to see if Pembrolizumab in combination with chemotherapy (carboplatin and gemcitabine) is safe and effective in treating patients with metastatic triple negative breast cancer. Pembrolizumab is a drug which may help the immune system to target and destroy cancer cells. Pembrolizumab has been approved by the FDA for the treatment of advanced melanoma and metastatic non-small cell lung cancer. However, it has not been approved as a treatment for breast cancer.

Conditions

Carcinoma Breast Stage IV

Keywords

Triple Negative Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate

  Evaluate antitumor activity by assessing the percentage of patients with evidence of complete response or partial response per RECIST 1.1 criteria.

  Up to 24 months

• Incidence of Treatment-Related Adverse Events

  The safety and tolerability of Pembrolizumab in Combination with Carboplatin and Gemcitabine will be evaluated from the results of reported signs and symptoms, scheduled physical examinations, vital sign measurements, and clinical laboratory test results.

  From the first dose of study treatment until 30 days after discontinuation of study treatment.

Secondary Outcomes (3)

• Clinical Benefit Rate

  Up to 24 months

• Progression Free Survival

  From the start of treatment until progressive disease or date of death, whichever occurs first (assessed up to 60 months.)

• Overall Survival

  From the start of treatment until death (assessed up to 60 months.)

Other Outcomes (3)

• Assessment of Association of PD-L1 Expression with Clinical Benefit Rate

  Up to 24 months

• Assessment of Association of PD-L1 Expression with Progression Free Survival

  Up to 24 months

• Assessment of Association of PD-L1 Expression with Overall Survival

  Up to 24 months

Study Arms (2)

Pembrolizumab with Standard Chemotherapy

EXPERIMENTAL

Pembrolizumab plus standard chemotherapy using carboplatin and gemcitabine.

Drug: Pembrolizumab; Drug: Carboplatin; Drug: Gemcitabine

Standard Chemotherapy Alone

ACTIVE COMPARATOR

Standard chemotherapy alone using carboplatin and gemcitabine.

Drug: Carboplatin; Drug: Gemcitabine

Interventions

Pembrolizumab DRUG

IV Infusion of 200 mg given on day one of each 21 day treatment cycle.

Also known as: MK-3475, Keytruda

Pembrolizumab with Standard Chemotherapy

Carboplatin DRUG

IV infusion of a calculated dose (AUC 2 mL/min) given on days one and eight of each 21 day treatment cycle.

Also known as: Paraplatin

Pembrolizumab with Standard Chemotherapy; Standard Chemotherapy Alone

Gemcitabine DRUG

IV infusion of 800 mg/m\^2 given on days one and eight of each 21 day treatment cycle.

Also known as: Gemzar

Pembrolizumab with Standard Chemotherapy; Standard Chemotherapy Alone

Eligibility Criteria

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

You may qualify if:

• Women diagnosed with pathologically confirmed metastatic triple negative invasive breast cancer (centrally confirmed immunophenotype negative for all three receptors ER, PR and HER2).
• Hormone receptor status (ER and PR) both ≤ 5% by immunohistochemistry, and HER2 status confirmed by means of immunohistochemistry (with 0 or 1+ indicating negative status) or fluorescence in situ hybridization (with amplification ratio \< 2.0 indicating negative status).
• Have either Evaluable disease, or have measurable clinical disease: Measurable disease, defined as at least 1 unidimensionally measurable lesion on a CT scan as defined by RECIST (version v1.1).
• Age \> 18 years.
• Disease stage: Unresectable metastatic disease.
• Patients received up to 2 prior regimens for their disease in the metastatic setting.
• Patients are candidates for chemotherapy with carboplatin and gemcitabine.
• ECOG performance status 0 - 2.
• Adequate organ function tests and hematologic indices within 10 days of registration.
• Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to registration. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Female subjects of childbearing potential must 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 childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year.
• Signed written Informed Consent in accordance with regulatory and institutional guidelines

You may not qualify if:

• Patients participating in another trial of an investigational agent within 4 weeks of the first dose of the study.
• Patients who received prior therapy using carboplatin/gemcitabine within 12 months prior to enrollment or subjects whose tumor progressed while on treatment with carboplatin or cisplatin.
• Patients with baseline grade 2 neuropathy.
• Patients with Hormone-receptor positive breast cancer (ER and/or PR \> 5%), and with HER-2 positive breast cancer (by means of immunohistochemistry with 3+ indicating positive status or fluorescence in situ hybridization with amplification ratio ≥2.0 indicating positive status).
• Diagnosis of immunosuppression or receiving steroid therapy or other immunosuppressive therapy within 4 weeks of the study.
• Active autoimmune disease or a documented history of autoimmune disease, or a syndrome that has required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thryoxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc) is not considered a form of systemic treatment. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects who require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjögren's syndrome will not be excluded from the study.
• Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
• Has had a prior monoclonal antibody 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.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
• If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Known additional malignancy that progressed and/or required treatment in the last 5 years. Except that for basal and squamous cell carcinoma of the skin or in situ cervical carcinoma that has completed potentially curative therapy.
• Life expectancy of less than 3 months.
• Patients known to be carriers of Human Immunodeficiency Virus (HIV1/2).
• Patients known to be carriers of hepatitis virus B and C.
• Prior therapy with an anti-programmed cell death 1 (PD-1), anti-programmed cell death 1 ligand (PDL-1), anti-PD-L2, anti-CD137 antibody, or anti-cytotoxic T-lymphocyte -associated antigen-4 (CTLA-4) antibody.

Sponsors & Collaborators

• Fox Chase Cancer Center: lead
• University of Wisconsin, Madison: collaborator

Study Sites (6)

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63130, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Duke University

Durham, North Carolina, United States

Location

Fox Chase Cancer Center - Philadelphia

Philadelphia, Pennsylvania, 19111-2497, United States

Location

University of Wisconsin

Madison, Wisconsin, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

pembrolizumab; Carboplatin; Gemcitabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Elias Obeid, MD

  Fox Chase Cancer Center

  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: April 25, 2016
• First Posted: April 28, 2016
• Study Start: May 31, 2016
• Primary Completion: May 1, 2026
• Study Completion: May 1, 2026
• Last Updated: July 4, 2025

Record last verified: 2025-07

Locations

US (6)