Rintatolimod, Celecoxib and Interferon Alpha 2b With Pembrolizumab For the Treatment of Patients With Metastatic or Unresectable Triple Negative Breast Cancer

NCT05756166 | Terminated Phase 1 DMC FDA Drug

• 3 other identifiers: I-3010822NCI-2023-01262P01CA234212
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/IIa trial tests the safety, side effects, and best dose of chemokine modulation therapy (CKM) (rintatolimod, celecoxib, and interferon alpha 2b) in combination with pembrolizumab for the treatment of patients with triple negative breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic) or that cannot be removed by surgery (unresectable). CKM drugs such as rintatolimod and interferon alpha 2b work to modify the immune response and tumor-related processes, including tumor cell growth, blood vessel growth, and metastasis. Celecoxib is an anti-inflammatory drug that can cause cell death and may reduce the growth of blood vessels tumors need to grow and spread. Immunotherapy such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving CKM therapy prior to pembrolizumab may direct the immune cells to the cancer cells and maximize the effectiveness of pembrolizumab in patients with metastatic or unresectable triple negative breast cancer.

Conditions

Anatomic Stage IV Breast Cancer AJCC v8; Metastatic Triple-Negative Breast Carcinoma; Unresectable Triple-Negative Breast Carcinoma

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events

  The dose limiting toxicities will be summarized by cohort using frequencies and relative frequencies.

  Up to 2 years

Secondary Outcomes (4)

• Progression-free survival

  From the start of post-chemokine modulation (CKM) therapy therapy until disease progression, death, or lst follow-up, assessed up to 2 years

• Overall response rate

  From the start of study treatment until end of treatment or disease progression/recurrence, assessed up to 2 years

• Overall survival

  From the start of post-CKM therapy until death due to any cause or last follow up, assessed up to 2 years

• Disease control rate

  Up to 2 years

Study Arms (2)

Cohort I (CKM, pembrolizumab)

EXPERIMENTAL

Patients receive rintatolimod IV, celecoxib PO, interferon alpha-2b IV on days 0, 1, and 2 of week 1 and days 7, 8, and 9 of week 2 on study. Patients receive pembrolizumab IV on day 9 and then every 3 weeks after that for up to 4 doses on study. Patients also undergo CT scan or MRI at screening and follow-up and undergo blood sample collection during screening and on study.

Procedure: Biospecimen Collection; Drug: Celecoxib; Procedure: Computed Tomography; Biological: Interferon Alpha-2; Procedure: Magnetic Resonance Imaging; Biological: Pembrolizumab; Drug: Rintatolimod

Cohort II (CMK, early pembrolizumab)

EXPERIMENTAL

Patients receive rintatolimod IV, celecoxib PO, and interferon alpha-2b IV on days 0, 1, and 2 of week 1 and days 7, 8, and 9 of week 2 on study. Patients receive pembrolizumab IV on day 2 of week 1 and then every 3 weeks beginning in week 4 on study. Patients also undergo CT scan or MRI at screening and follow-up, undergo blood sample collection during screening and on study, and may undergo tumor biopsy at screening and follow-up.

Procedure: Biopsy; Procedure: Biospecimen Collection; Drug: Celecoxib; Procedure: Computed Tomography; Biological: Interferon Alpha-2; Procedure: Magnetic Resonance Imaging; Biological: Pembrolizumab; Drug: Rintatolimod

Interventions

Biopsy PROCEDURE

Undergo tumor biopsy

Also known as: BIOPSY_TYPE, Bx

Cohort II (CMK, early pembrolizumab)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Cohort I (CKM, pembrolizumab); Cohort II (CMK, early pembrolizumab)

Celecoxib DRUG

Given PO

Also known as: Benzenesulfonamide, 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-, Celebrex, SC-58635, YM 177

Cohort I (CKM, pembrolizumab); Cohort II (CMK, early pembrolizumab)

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized Tomography, CT, CT Scan, tomography

Cohort I (CKM, pembrolizumab); Cohort II (CMK, early pembrolizumab)

Interferon Alpha-2 BIOLOGICAL

Given IV

Also known as: Alpha-2-Interferon, Alpha-2a Interferon, IFN-Alpha-2, IFN-AlphaA, IFNA2, IFNA2 Protein, Interferon Alpha 2, Interferon Alpha 2a, Interferon Alpha 2b, Interferon Alpha A, Interferon Alpha-A, LeIF A

Cohort I (CKM, pembrolizumab); Cohort II (CMK, early pembrolizumab)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging

Cohort I (CKM, pembrolizumab); Cohort II (CMK, early pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Cohort I (CKM, pembrolizumab); Cohort II (CMK, early pembrolizumab)

Rintatolimod DRUG

Given IV

Also known as: Ampligen, Atvogen

Cohort I (CKM, pembrolizumab); Cohort II (CMK, early pembrolizumab)

Eligibility Criteria

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

You may qualify if:

• Age \>= 18 years of age
• Have pathologically confirmed diagnosis of PDL-1-negative or PDL1 positive 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. Note: For cohort 1 and cohort 2: Patient with accessible tumor will be offered optional pre-treatment and post-treatment biopsies. Biopsies are mandatory for cohort 3
• 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
• 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 glutamic pyruvic transaminase \[SGPT\]) =\< 2.5 X institutional ULN

You may not qualify if:

• Patients currently treated with systemic immunosuppressive agents, including steroids (greater 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. While our published clinical studies involving short-term CKM did not indicate increased risk of cardiac events, the CKM can induce flu-like symptoms, providing justification for its avoidance in patients with recent cardiac events
• Patients with a New York Heart Association classification of III or IV
• Patients with a history of stroke
• 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 drug (NSAIDs) or any drugs administered on protocol
• 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
• Has a known history of human immunodeficiency virus (HIV) infection
• Concurrent active hepatitis B (defined as hepatitis B antigen \[HBsAg\] positive and/or detectable hepatitis B virus \[HBV\] deoxyribonucleic acid \[DNA\]) and hepatitis C virus (defined as anti-hepatitis C virus \[HCV\] antibody \[Ab\] positive and detectable HCV ribonucleic acid \[RNA\]) infection. Note: Hepatitis B and C screening tests are not required unless known history of HBV and HCV infection

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

Biopsy; Specimen Handling; Celecoxib; Interferon alpha-2; Magnetic Resonance Spectroscopy; pembrolizumab; poly(I).poly(c12,U)

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; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Interferon-alpha; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Ellis Levine, MD

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2023
• First Posted: March 6, 2023
• Study Start: February 16, 2024
• Primary Completion: April 8, 2025
• Study Completion: June 19, 2025
• Last Updated: June 24, 2025

Record last verified: 2025-06

Locations

US (1)