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Chemokine Modulation Therapy and Pembrolizumab in Treating Participants With Metastatic Triple-Negative 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. Identifier: NCT03599453
Recruitment Status : Recruiting
First Posted : July 26, 2018
Last Update Posted : January 2, 2020
National Cancer Institute (NCI)
AIM ImmunoTech Inc.
Information provided by (Responsible Party):
Roswell Park Cancer Institute

Brief Summary:
This pilot trial studies how well chemokine modulation therapy works when given prior to pembrolizumab in treating participants with triple-negative breast cancer that has spread to other places in the body. Drugs used in chemokine modulation therapy, such as celecoxib, recombinant interferon alfa-2b, and rintatolimod, work by unleashing or enhancing the cancer immune responses that already exist by either blocking inhibitory molecules or by activating stimulatory molecules. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Giving chemokine modulation therapy before pembrolizumab may work better in treating participants with metastatic triple-negative breast cancer

Condition or disease Intervention/treatment Phase
Triple -Negative Breast Cancer Estrogen Receptor Negative HER2/Neu Negative Anatomic Stage IV Breast Cancer AJCC Progesterone Receptor Negative Procedure: Biopsy Procedure: Chemokine Modulation Therapy Drug: Celecoxib Biological: Recombinant Interferon Alfa-2b Drug: Rintatolimod Biological: Pembrolizumab Early Phase 1

Detailed Description:


-To evaluate the increase of CD8+ infiltration into tumor microenvironment after pre-treatment CKM regime


  • To evaluate the overall response rate (ORR) to the combination therapy per RECIST v1.1
  • To evaluate the efficacy of the chemokine modulation (CKM) in combination with pembrolizumab in patients with metastatic triple negative breast cancer (mTNBC) as compared to historic outcomes of pembrolizumab and other anti-PD1/PD-L1 therapies alone, as determined by secondary measures of efficacy including progression-free survival (PFS), overall survival (OS), and disease control rate (DCR).
  • To evaluate the safety profile of CKM regimen given as pre-treatment to pembrolizumab therapy in metastatic breast cancer patients using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.


  • Examine the immune analysis profile of CKM and pembrolizumab combination.
  • Examine the relationship of infiltrating CD4+ and CD8+ T cells and other immune and genetic markers, and their associated PD-1, CD45RA or CD45RO levels.
  • Correlate PD-L1 expression within both neoplastic and nonneoplastic stromal elements of the tumor microenvironment to PFS, OS, ORR and adverse events (AEs).
  • Correlate Immune Panel results with ORR, PFS, OS and AEs.
  • Comparison of response assessment criteria for a prospective analysis


Participants undergo pre-treatment biopsy. Participants then undergo chemokine modulation therapy consisting of celecoxib orally (PO) twice daily (BID), recombinant interferon alfa-2b intravenously (IV) over 20 minutes, and rintatolimod IV over 30-60 minutes on days -11 to -9, and -4 to -2. Participants then undergo additional biopsy. Following biopsy and chemokine modulation therapy, participants receive pembrolizumab IV over 30 minutes on day 1. After completion of study treatment, participants are followed up for 90 days and then every 6 months for up to 2 years.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 6 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Open Label Clinical Trial Evaluating the Safety and Efficacy of Chemokine Modulation to Enhance the Effectiveness of Pembrolizumab in Patients With Metastatic Triple Negative Breast Cancer
Actual Study Start Date : January 9, 2019
Estimated Primary Completion Date : June 6, 2021
Estimated Study Completion Date : July 6, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Treatment (chemokine modulation therapy)
Participants undergo pre-treatment biopsy. Participants then undergo chemokine modulation therapy consisting of celecoxib PO BID, recombinant interferon alfa-2b IV over 20 minutes, and rintatolimod IV over 30-60 minutes on days -11 to -9, and -4 to -2. Participants then undergo additional biopsy. Following biopsy and chemokine modulation therapy, participants receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity.
Procedure: Biopsy
Undergo Biopsy

Procedure: Chemokine Modulation Therapy
Undergo chemokine modulation therapy

Drug: Celecoxib
Given by mouth
Other Name: Celebrex, YM 177, Benzenesulfonamide

Biological: Recombinant Interferon Alfa-2b
Given intravenously
Other Name: Alfatronol, Glucoferon, Heberon Alfa, IFN alpha-2B, Interferon alfa 2b, Intron A, recombinant interferon alfa-2b, Recombinant Interferon Alfa-2b, Sch

Drug: Rintatolimod
Given intravenously
Other Name: 38640-92-5, 616524, Ampligen, Ampligen, Atvogen, Poly(I).Poly(c12,U), Poly(Inosinic Acid) Poly(Cytidylic(12), Uridylic)Acid, RINTATOLIMOD, Rintatolimod

Biological: Pembrolizumab
Given intravenously
Other Name: Immunoglobulin G4,Keytruda, Lambrolizumab

Primary Outcome Measures :
  1. Overall response rate (ORR) as measured by immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) criteria 1.1 [ Time Frame: Up to 2 years ]
    Will be assessed using a Simon two-stage minimax design.

Secondary Outcome Measures :
  1. Progression-free survival (PFS) as measured by irRECIST 1.1 criteria [ Time Frame: Up to 2 years ]
    Will be assessed using a Simon two-stage minimax design

  2. Overall survival (OS) as measured by irRECIST 1.1 criteria [ Time Frame: Up to 2 years ]
  3. Disease control rate (DCR) as measured by irRECIST 1.1 criteria [ Time Frame: Up to 2 years ]
    Will be assessed using a Simon two-stage minimax design

  4. Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 [ Time Frame: Up to 2 years ]
    Adverse events (AEs), serious AEs (SAEs), and toxicities will be summarized by attribution (overall and related/unrelated to treatment) and grade using frequencies and relative frequencies

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 and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Have pathologically confirmed diagnosis of unresectable or metastatic TNBC with no curative treatment options
  • Have been informed of other treatment options
  • Patient has lesion that can be biopsied and is willing to undergo the procedure as part of the protocol
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 1
  • Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. 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
  • Ability to swallow and retain oral medication
  • Have measurable disease per RECIST 1.1 criteria present
  • Any line of therapy allowed, radiologically confirmed progression on prior therapy
  • No cancer-directed therapy for at least 3 weeks prior to study treatment (bone-directed therapies are allowed)
  • Platelets >= 100,000/uL
  • Hemoglobin >= 9.0 g/dL
  • Absolute neutrophil count (ANC) >= 1500/uL
  • Total bilirubin =< institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN
  • Creatinine < ULN OR creatinine clearance >= 50 mL/min per Cockcroft-Gault Equation for patients with creatinine levels greater than ULN
  • Participant or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Exclusion Criteria:

  • Patients currently treated with systemic immunosuppressive agents, including steroids (> than equivalent of 10 mg daily of prednisone), are ineligible until 3 weeks after removal from immunosuppressive treatment (inhaled steroids are allowed)
  • Patients with active autoimmune disease or history of transplantation
  • Pregnant or nursing female participants
  • Unwilling or unable to follow protocol requirements
  • Patients with known serious mood disorders (Major depression diagnosis is an exclusion. Other stable mood disorders on stable therapy for > 6 months or not requiring therapy may be allowed after consultation with PI
  • Cardiac risk factors including:
  • Patients experiencing cardiac event(s) (acute coronary syndrome, myocardial infarction, or ischemia) within 3 months of signing consent
  • Patients with a New York Heart Association classification of III or IV
  • History of upper gastrointestinal ulceration, upper gastrointestinal bleeding, or upper gastrointestinal perforation within the past 3 years
  • Prior allergic reaction or hypersensitivity to nonsteroidal antiinflammatory drugs (NSAIDs) or any drugs administered on protocol
  • Prior immunotherapy with anti-PD1/PDL1 therapy for the mTNBC
  • Patients are ineligible if they plan on regular use of NSAIDs at any dose more than 2 times per week (on average) or aspirin at more than 325 mg at least three times per week, on average. Low-dose aspirin not exceeding 100 mg/day is permitted. Patients who agree to stop regular NSAIDs or higher dose aspirin are eligible and no wash out period is required
  • Any condition which in the Investigator's opinion deems the participant an unsuitable candidate to receive study drug
  • Any patients with a positive Antinuclear Antibodies test will be excluded from study

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 identifier (NCT number): NCT03599453

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Contact: Ask RPCI 877-275-7724

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United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
Sponsors and Collaborators
Roswell Park Cancer Institute
National Cancer Institute (NCI)
AIM ImmunoTech Inc.
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Principal Investigator: Shipra Gandhi, MD Roswell Park Cancer Institute

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Responsible Party: Roswell Park Cancer Institute Identifier: NCT03599453    
Other Study ID Numbers: I 62218
First Posted: July 26, 2018    Key Record Dates
Last Update Posted: January 2, 2020
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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.: Yes
Additional relevant MeSH terms:
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Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Interferon alpha-2
Poly I-C
Antineoplastic Agents, Immunological
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors