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Chemotherapy with or without Tocilizumab for the Initial Treatment of Unresectable, Locally Recurrent, or Metastatic Triple Negative or ER and PR-low Breast Cancer
Trial Status: active
This phase II trial tests the effectiveness of standard of care (SOC) chemotherapy with or without tocilizumab in treating patients with triple negative or estrogen receptor (ER) and progesterone receptor (PR) low breast cancer that cannot be removed by surgery (unresectable), has come back after a period of improvement (locally recurrent), or has spread from where it first started to other places in the body (metastatic). Triple negative means that the tumor tests negative for all three proteins, estrogen, progesterone and HER2 found inside tumor cells. Interleukin-6 (IL-6) is a group of related proteins made by leukocytes and other cells in the body. IL-6 is made mainly by lymphocytes, a type of immune cell that is made in the bone marrow and is found in the blood, and causes them to make more antibodies to boost the immune system in cancer therapy. Tocilizumab is a monoclonal antibody that binds to receptors for a IL-6 protein. This may help lower the body’s immune response and reduce inflammation. Chemotherapy drugs work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving SOC chemotherapy with tocilizumab may kill more tumor cells in patients with metastatic triple negative or ER and PR-low breast cancer.
Inclusion Criteria
>= 18 years old at the time of informed consent
Ability to provide written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization
Locally recurrent (not amenable to local therapy with curative intent) or metastatic breast cancer that is triple negative or ER-low (ER and PR ≤ 9% weak staining)
Received up to 2 prior therapies for metastatic disease
* Prior (neo)adjuvant therapy will be considered one line of therapy for metastatic disease in patients who recur while on or within 12 months of completion of (neo)adjuvant therapy
* Participation in this protocol as either first, second and third-line therapy is allowed
Planned standard of care chemotherapy based on National Comprehensive Cancer Network (NCCN) guidelines
* Single agent therapy is preferred but use of combination regimens considered SOC by NCCN is allowed
* Chemotherapy delivered via a SOC antibody-drug conjugate is allowed but antibody-drug conjugates (ADCs) may not be used in combination with other agents
Patients with tumors that are PD-L1+ (CPS > 10) must have had prior exposure to an immune checkpoint inhibitor in the metastatic setting
* Patients who received (neo)adjuvant immuno-oncology (IO) therapy and progress while on or within 12 months of completion of (neo)adjuvant IO therapy may participate without additional IO treatment
* Patients with major contraindications to immune therapy, may participate without IO exposure regardless of PD-L1 status in the first line setting
* PD-L1 status is not required for patients in the second line setting
Measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
Patients with treated, asymptomatic central nervous system (CNS) disease may participate if the patient is > 4 weeks from completion of CNS therapy (radiation and/or surgery), is clinically stable at the time of study entry, and is receiving a stable or decreasing dose of corticosteroid therapy. Brain MRI or head CT is required at screening for patients with known brain metastases
Total bilirubin =< upper limit of normal (ULN) (except in patients with documented Gilbert’s disease, who must have a total bilirubin =< 3.0 mg/dL)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 5.0 x ULN
Creatinine clearance of >= 50 mL/min using the Cockcroft-Gault formula
Absolute neutrophil count (ANC) >= 1.5 K/mm^3
Platelets >= 100 K/mm^3
Hemoglobin (Hgb) >= 9.0 g/dL
Women of childbearing potential must have a negative pregnancy test within 14 days of protocol registration. Women are considered to have childbearing potential (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) unless they meet one of the following criteria:
* Has undergone a hysterectomy or bilateral oophorectomy; or
* Has been naturally amenorrheic for at least 24 consecutive months
Women of childbearing potential and men must agree to use effective contraception throughout the study and for 6 months after the last study treatment. Note: Acceptable methods of birth control include abstinence, partner with previous vasectomy, placement of an intrauterine device (IUD), condom with spermicidal foam/gel/film/cream/suppository, diaphragm or cervical vault cap, or hormonal birth control (pills or injections)
Exclusion Criteria
Prior treatment with or known contraindication to treatment with tocilizumab or other IL-6/IL-6R targeted agent
Active infection requiring parenteral antibiotics
Concurrent use of methotrexate or systemic corticosteroids
Active or symptomatic CNS disease
Patients with HER2+ disease. HER2 will be considered positive if scored 3+ by immunohistochemistry (IHC) or 2+ by IHC associated with a fluorescence in situ hybridization (FISH) ratio of > 2.0 or > 6 total HER2 gene copies per cell
Patients with active malignancy other than breast cancer. Patients with prior malignancies without recurrence after standard treatment will not be excluded
Radiation therapy within 2 weeks of registration
Hormone therapy within 2 weeks of registration
Additional locations may be listed on ClinicalTrials.gov for NCT05846789.
I. Evaluate the efficacy of tocilizumab when added to SOC chemotherapy in Black and non-Black patients with metastatic triple negative or ER low breast cancer.
II. Compare efficacy across race-based cohorts.
SECONDARY OBJECTIVES:
I. Evaluate safety in all enrolled patients.
II. Evaluate differences in inflammatory pathways between Black and non-Black patients.
III. Among Black patients, evaluate the impact of Duffy genotype on efficacy.
TERTIARY OBJECTIVES:
I. Collect circulating blood (whole blood, plasma, and peripheral blood mononuclear cell [PBMC]) samples to explore biomarkers of response and biologic activity.
II. Collect pre- and post-treatment tumor samples to explore biomarkers of response and biologic activity.
III. Collect data to assess neighborhood socioeconomic status and individual social determinants of health to explore their impact on immune signaling and response.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive SOC chemotherapy as determined by investigator discretion on study in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive tocilizumab intravenously (IV) over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Starting in week 2, patients also receive SOC chemotherapy as determined by investigator discretion on study in the absence of disease progression or unacceptable toxicity.
All patients undergo blood sample collection, computed tomography (CT) scan, positron emission tomography (PET)/CT scan, bone scan and/or magnetic resonance imaging (MRI) throughout study. Additionally, patients may undergo biopsy of tumor during screening and on study, and optionally at end of study.
After completion of study treatment, patients are follow up for up to 30 days.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationIndiana University/Melvin and Bren Simon Cancer Center
