Chemokine Modulation Therapy and Pembrolizumab in Treating Participants With Metastatic Triple-Negative Breast Cancer
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ClinicalTrials.gov Identifier: NCT03599453 |
Recruitment Status :
Active, not recruiting
First Posted : July 26, 2018
Last Update Posted : January 23, 2023
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Condition or disease | Intervention/treatment | Phase |
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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 |
PRIMARY OBJECTIVES:
-To evaluate the increase of CD8+ infiltration into tumor microenvironment after pre-treatment CKM regime
SECONDARY OBJECTIVES:
- 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.
EXPLORATORY OBJECTIVES:
- 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
OUTLINE:
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.
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 8 participants |
Allocation: | N/A |
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 |
Actual Primary Completion Date : | September 2, 2020 |
Estimated Study Completion Date : | June 2, 2023 |

Arm | Intervention/treatment |
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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.
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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 |
- 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.
- 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
- Overall survival (OS) as measured by irRECIST 1.1 criteria [ Time Frame: Up to 2 years ]
- 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
- 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

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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
- 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

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): NCT03599453
United States, New York | |
Roswell Park Cancer Institute | |
Buffalo, New York, United States, 14263 |
Principal Investigator: | Shipra Gandhi, MD | Roswell Park Cancer Institute |
Responsible Party: | Roswell Park Cancer Institute |
ClinicalTrials.gov Identifier: | NCT03599453 |
Other Study ID Numbers: |
I 62218 |
First Posted: | July 26, 2018 Key Record Dates |
Last Update Posted: | January 23, 2023 |
Last Verified: | January 2023 |
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 |
Product Manufactured in and Exported from the U.S.: | Yes |
Breast Neoplasms Triple Negative Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Interferons Interferon-alpha Interferon alpha-2 poly(I).poly(c12,U) Poly I-C Celecoxib Pembrolizumab Immunoglobulins Immunoglobulin G |
Benzenesulfonamide Antineoplastic Agents, Immunological Antineoplastic Agents Antiviral Agents Anti-Infective Agents Immunologic Factors Physiological Effects of Drugs Anti-Inflammatory Agents, Non-Steroidal Analgesics, Non-Narcotic Analgesics Sensory System Agents Peripheral Nervous System Agents Anti-Inflammatory Agents Antirheumatic Agents Cyclooxygenase 2 Inhibitors |