Clinical Trial: NCT03599453 - My Cancer Genome

NCT03599453

Description:

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

Related Conditions:

Breast Carcinoma

Recruiting Status:

Active, not recruiting

Phase:

Early Phase 1

URL:

https://clinicaltrials.gov/show/NCT03599453

Trial Eligibility

Document

Title

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

Clinical Trial IDs

ORG STUDY ID: I 62218
NCT ID: NCT03599453

Conditions

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

Interventions

Drug	Synonyms	Arms
Celecoxib	Celebrex, YM 177, Benzenesulfonamide	Treatment (chemokine modulation therapy)
Recombinant Interferon Alfa-2b	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	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	Immunoglobulin G4,Keytruda, Lambrolizumab	Treatment (chemokine modulation therapy)

Purpose

Detailed Description

      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.

Trial Arms

Name	Type	Description	Interventions
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.	Celecoxib Recombinant Interferon Alfa-2b Rintatolimod Pembrolizumab

Eligibility Criteria

        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

Maximum Eligible Age:	N/A
Minimum Eligible Age:	18 Years
Eligible Gender:	Female
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	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
Safety Issue:
Description:	Will be assessed using a Simon two-stage minimax design.

Secondary Outcome Measures

Measure:	Progression-free survival (PFS) as measured by irRECIST 1.1 criteria
Time Frame:	Up to 2 years
Safety Issue:
Description:	Will be assessed using a Simon two-stage minimax design

Measure:	Overall survival (OS) as measured by irRECIST 1.1 criteria
Time Frame:	Up to 2 years
Safety Issue:
Description:

Measure:	Disease control rate (DCR) as measured by irRECIST 1.1 criteria
Time Frame:	Up to 2 years
Safety Issue:
Description:	Will be assessed using a Simon two-stage minimax design

Measure:	Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Time Frame:	Up to 2 years
Safety Issue:
Description:	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

Details

Phase:	Early Phase 1
Primary Purpose:	Interventional
Overall Status:	Active, not recruiting
Lead Sponsor:	Roswell Park Cancer Institute

Last Updated

June 2, 2021

Clinical Trials /

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