Toci +/- SOC Chemo for Metastatic Triple Negative and ER-positive, HER2-negative Breast Cancers

A Pragmatic Phase II Trial of Chemotherapy +/- Tocilizumab for Metastatic Triple Negative and ER-positive, HER2-negative Breast Cancers

This is a randomized Phase II study of standard of care (SOC) chemotherapy monotherapy vs. SOC chemotherapy combined with tocilizumab biosimilar in Black and non-Black patients with metastatic triple negative and ER-positive, HER2-negative breast cancer.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Breast Cancer; Triple Negative Breast Cancer; ER Positive, HER2 Negative Breast Cancer; Estrogen-receptor-low Breast Cancer
• Intervention / Treatment: Drug: SOC Chemotherapy; Drug: Tocilizumab/Tocilizumab Biosimilar

Detailed Description

Randomized phase II using a one-stage design. Patients are randomized 1:1 to either the monotherapy or combination arms. This requires 42 patients (21 per treatment arm) for each race-based cohort. All the calculations are based on Smart-Design-Indiana at https://iusccc.shinyapps.io/SmartDesign-Indiana/.

• Study Type: Interventional
• Enrollment (Estimated): 168
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xin Bryan, RN; Phone Number: 317-274-5495; Email: zhongx@iupui.edu

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University
      • Principal Investigator: Shipra Gandhi, MD
      • Contact: Carlos Aguilera, BA; Phone Number: 404-778-1868; Email: winshipcto@emory.edu
  • Indiana
    • Carmel, Indiana, United States, 46032
      • Recruiting
      • IU Health Joe and Shelly Schwarz Cancer Center
      • Contact: Xin Bryan, RN; Phone Number: 317-274-5495; Email: zhongx@iupui.edu
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Sidney and Lois Eskenazi Hospital
      • Contact: Xin Bryan, RN; Phone Number: 317-274-5495; Email: zhongx@iupui.edu
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Indiana University Melvin and Bren Simon Comprehensive Cancer Center
      • Contact: Xin Bryan, RN; Phone Number: 317-274-5495; Email: zhongx@iupui.edu
      • Principal Investigator: Kathy Miller, MD
  • Kentucky
    • Lexington, Kentucky, United States, 40506
      • Recruiting
      • University of Kentucky-Lexington
      • Contact: Rayli Pichardo, MD; Phone Number: 859-257-2862; Email: rcpi226@uky.edu
      • Contact: Amanda Cavinder, BS; Phone Number: 859-562-0539; Email: Amanda.Cavinder@uky.edu;
  • New York
    • Buffalo, New York, United States, 14203
      • Recruiting
      • Roswell Park Comprehensive Cancer Center
      • Contact: Lindsay Moshides, MS; Phone Number: 6328 716-854-1300; Email: Lindsay.Moshides@RoswellPark.org
      • Principal Investigator: Sheheryar Kabraji, MD
  • North Carolina
    • Durham, North Carolina, United States, 27708
      • Recruiting
      • Duke University
      • Principal Investigator: Alexandra Thomas, MD
      • Contact: Samantha Womack, BA; Phone Number: 919-660-1278; Email: sam.womack@duke.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. ≥ 18 years old at the time of informed consent
2. Ability to provide written informed consent and HIPAA authorization
3. Locally recurrent (not amenable to local therapy with curative intent) or metastatic breast cancer that is triple negative or ER-positive (ER and PR ≤ 1% weak staining)

4. For patients with TNBC

   1. Received up to 2 prior therapies for metastatic disease
   2. Prior (neo)adjuvant chemotherapy 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.
   3. Patients with TNBC whose tumors are PD-L1+ (CPS > 10) must have had prior exposure to an immune checkpoint inhibitor in the metastatic setting.
   4. Patients who received (neo)adjuvant IO therapy and progress while on or within 12 months of completion of (neo)adjuvant IO therapy may participate without additional IO treatment.
   5. Patients with major contraindications to immune therapy, may participate without IO exposure regardless of PD-L1 status in the first line setting.
   6. PD-L1 status is not required for patients beyond the first line setting.
   7. Participation in this protocol as either first, second and third-line therapy is allowed

5. For patients with ER- positive, HER2-negative breast cancer

   1. Must have received prior hormone therapy + CDKi in the adjuvant or metastatic setting. There is no limit on the number of prior hormone therapy regimens.
   2. May have received up to 3 prior chemotherapies for metastatic disease.
   3. Prior (neo)adjuvant chemotherapy 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.
   4. Participation in this protocol as either first, second, third, or fourth-line therapy is allowed

6. Planned standard of care chemotherapy based on NCCN guidelines.

   1. Single agent therapy is preferred but use of combination regimens considered SOC by NCCN is allowed.
   2. Chemotherapy delivered via a SOC antibody-drug conjugate is allowed but ADCs may not be used in combination with other chemotherapy agents.
7. Measurable disease based on RECIST 1.1 criteria.
8. ECOG PS 0 or 1
9. Patients with treated, asymptomatic 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 stable or decreasing dose of corticosteroids. Brain MRI or head CT is required at screening for patients with known brain metastases.

10. Adequate organ function as indicated by:

    1. Total bilirubin < ULN (except in patients with documented Gilbert's disease, who must have a total bilirubin < 3.0 mg/dL)
    2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 5.0 x ULN
    3. Creatinine clearance of > 50 mL/min using the Cockcroft-Gault formula
    4. Absolute neutrophil count (ANC) > 1.2 K/mm3
    5. Platelets > 75 K/ mm3
    6. Hgb > 9.0 g/dL

11. 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:

    1. Has undergone a hysterectomy or bilateral oophorectomy; or
    2. Has been naturally amenorrheic for at least 24 consecutive months.
12. 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:

1. Prior treatment with or known contraindication to treatment with tocilizumab biosimilar or other IL-6/IL-6R targeted agent
2. Active infection requiring parenteral antibiotics
3. Concurrent use of methotrexate or systemic corticosteroids other than stable or decreasing doses for management of CNS involvement
4. Active or symptomatic CNS disease
5. Patients with HER2+ disease Note: 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.
6. Patients with active malignancy other than breast cancer. Patients with prior malignancies without recurrence after standard treatment will not be excluded
7. Radiation therapy within 2 weeks of registration
8. Hormone therapy within 2 weeks of registration
9. Planned treatment with Olaparib or other PARP inhibitor.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Black Monotherapy	Drug: SOC Chemotherapy; SOC Chemotherapy will be given AUC 6 IV q3 weeks for a maximum of 9 infusions.
Experimental: Black Combination treatment	Drug: SOC Chemotherapy; SOC Chemotherapy will be given AUC 6 IV q3 weeks for a maximum of 9 infusions.; Drug: Tocilizumab/Tocilizumab Biosimilar; Tocilizimab/Tocilizumab Biosimilar 8 mg/ actual body weight in kg IV q4 weeks
Active Comparator: Non-Black Monotherapy	Drug: SOC Chemotherapy; SOC Chemotherapy will be given AUC 6 IV q3 weeks for a maximum of 9 infusions.
Experimental: Non-Black Combination treatment	Drug: SOC Chemotherapy; SOC Chemotherapy will be given AUC 6 IV q3 weeks for a maximum of 9 infusions.; Drug: Tocilizumab/Tocilizumab Biosimilar; Tocilizimab/Tocilizumab Biosimilar 8 mg/ actual body weight in kg IV q4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate		through study completion (i.e. up to 2 years)
Progression-free survival		through study completion (i.e. up to 2 years)
Efficacy of tocilizumab biosimilar in Black and non-Black patients	efficacy defined as using the difference in difference approach across race based cohorts	through study completion (i.e. up to 2 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the differences in inflammatory pathways between Black and non-Black patients	Tumor PZP, IL-6, and phosphoSTAT3	Baseline
Evaluate the impact of Duffy genotype on efficacy in Black patients	Tumor PZP, IL-6, and phosphoSTAT3 between Duffy-null, Duffy-heterozygous, and Duffy-wild type	Baseline
Safety of SOC chemotherapy monotherapy compared to SOC chemotherapy combined with tocilizumab/tocilizumab biosimilar using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v 5.0		through study completion (i.e. up to 2 years)

Collaborators and Investigators

• Sponsor: Kathy Miller
• Collaborators: Genentech, Inc.; Susan G. Komen Breast Cancer Foundation; Breast Cancer Research Foundation
• Investigators: Principal Investigator: Kathy Miller, MD, Indiana University

Study record dates

Study Major Dates

• Study Start (Actual): July 2, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: April 27, 2023
• First Submitted That Met QC Criteria: April 27, 2023
• First Posted (Actual): May 6, 2023

Study Record Updates

• Last Update Posted (Actual): September 3, 2026
• Last Update Submitted That Met QC Criteria: September 1, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: Breast Cancer; Phase II
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Antineoplastic Agents; tocilizumab
• Other Study ID Numbers: CTO-IUSCCC-0817

Drug and device information, study documents

• 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.: No