Chemokine Modulation Therapy and Pembrolizumab in Treating Participants With Metastatic Triple-Negative Breast Cancer

NCT03599453 | Completed Early Phase 1 DMC FDA Drug

• 1 other identifier: I 62218
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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

Conditions

Triple -Negative Breast Cancer; Estrogen Receptor Negative; HER2/Neu Negative; Anatomic Stage IV Breast Cancer AJCC; Progesterone Receptor Negative

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR) as measured by immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) criteria 1.1

  Will be assessed using a Simon two-stage minimax design.

  Up to 2 years

Secondary Outcomes (4)

• Progression-free survival (PFS) as measured by irRECIST 1.1 criteria

  Up to 2 years

• Overall survival (OS) as measured by irRECIST 1.1 criteria

  Up to 2 years

• Disease control rate (DCR) as measured by irRECIST 1.1 criteria

  Up to 2 years

• Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

  Up to 2 years

Study Arms (1)

Treatment (chemokine modulation therapy)

EXPERIMENTAL

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; Procedure: Chemokine Modulation Therapy; Drug: Celecoxib; Biological: Recombinant Interferon Alfa-2b; Drug: Rintatolimod; Biological: Pembrolizumab

Interventions

Biopsy PROCEDURE

Undergo Biopsy

Treatment (chemokine modulation therapy)

Chemokine Modulation Therapy PROCEDURE

Undergo chemokine modulation therapy

Treatment (chemokine modulation therapy)

Celecoxib DRUG

Given by mouth

Also known as: Celebrex, YM 177, Benzenesulfonamide

Treatment (chemokine modulation therapy)

Recombinant Interferon Alfa-2b BIOLOGICAL

Given intravenously

Also known as: Alfatronol, Glucoferon, Heberon Alfa, IFN alpha-2B, Interferon alfa 2b, Intron A, recombinant interferon alfa-2b, Recombinant Interferon Alfa-2b, Sch

Treatment (chemokine modulation therapy)

Rintatolimod DRUG

Given intravenously

Also known as: 38640-92-5, 616524, Ampligen, Ampligen, Atvogen, Poly(I).Poly(c12,U), Poly(Inosinic Acid) Poly(Cytidylic(12), Uridylic)Acid, RINTATOLIMOD, Rintatolimod

Treatment (chemokine modulation therapy)

Pembrolizumab BIOLOGICAL

Given intravenously

Also known as: Immunoglobulin G4,Keytruda, Lambrolizumab

Treatment (chemokine modulation therapy)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• AIM ImmunoTech Inc.: collaborator

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

Biopsy; Celecoxib; Benzenesulfonamides; Introns; Interferon alpha-2; Neurofibromin 2; poly(I).poly(c12,U); Uridine Monophosphate; pembrolizumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; DNA, Intergenic; Genome Components; Genome; Genetic Structures; Genetic Phenomena; Gene Components; Genes; Interferon-alpha; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Membrane Proteins; Tumor Suppressor Proteins; Neoplasm Proteins; Uracil Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides

Study Officials

• Shipra Gandhi, MD

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2018
• First Posted: July 26, 2018
• Study Start: January 9, 2019
• Primary Completion: September 2, 2020
• Study Completion: March 21, 2023
• Last Updated: July 18, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)