Phase II Trial of Carboplatin +/- Tocilizumab for Metastatic Triple Negative and ER-low Breast Cancers

A Phase II Trial of Carboplatin +/- Tocilizumab as Initial Therapy for Metastatic Triple Negative and ER-low Breast Cancers

This is a randomized Phase II study of carboplatin monotherapy vs. carboplatin combined with tocilizumab in in Black and non-Black patients with metastatic triple negative or ER low breast cancer.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Breast Cancer; Triple Negative Breast Cancer; Estrogen-receptor-low Breast Cancer
• Intervention / Treatment: Drug: Carboplatin; Drug: Tocilizumab

Detailed Description

Randomized phase II using a two-stage Bayesian optimal phase II two-arm design (BOP2). Patients are randomized 1:1 to either the monotherapy or combination arms. This requires 42 patients (21 per treatment arm) in stage I for each race-based cohort. If the no. of response in experimental - no. of response in control is no greater than -1, the trial is early stopped at stage I for futility. Otherwise, additional 42 patients for each race-based cohort will be enrolled and randomized to the study in stage II.

• 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
  • Indiana
    • Carmel, Indiana, United States, 46032
      • Recruiting
      • IU Health Joe and Shelly Schwarz Cancer Center
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Sidney and Lois Eskenazi Hospital
    • 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

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-low (ER and PR ≤ 9% weak staining)

4. No prior chemotherapy for metastatic disease

   a. Prior (neo)adjuvant therapy must have been completed at least 12 months from diagnosis of unresectable locally recurrent or metastatic disease.

5. Measurable disease based on RECIST 1.1 criteria.

6. Disease amenable to and consent for study-specific biopsy

   a. NOTE: If no disease amenable to biopsy is present at the time of second biopsy, subjects may continue participation in the study and further study specific biopsies will not be required.

7. ECOG PS 0 or 1
8. 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 a stable or decreasing dose of corticosteroid therapy. Brain MRI or head CT is required at screening for patients with known brain metastases.

9. 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) > 1.5 K/mm3
   5. Platelets > 100 K/ mm3
   6. Hgb > 9.0 g/dL

10. 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.
11. 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 or other IL-6/IL-6R targeted agent
2. Patients who are PD-L1 positive (CPS ≥ 10), unless they have a clear contraindication to pembrolizumab therapy.
3. Active infection requiring parenteral antibiotics
4. Concurrent use of methotrexate or systemic corticosteroids
5. Active or symptomatic CNS disease
6. 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.
7. Patients with active malignancy other than breast cancer. Patients with prior malignancies without recurrence after standard treatment will not be excluded
8. Radiation therapy within 2 weeks of registration
9. Hormone therapy within 2 weeks of registration

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: Carboplatin; Carboplatin will be given AUC 6 IV q3 weeks for a maximum of 9 infusions.
Experimental: Black Combination treatment	Drug: Carboplatin; Carboplatin will be given AUC 6 IV q3 weeks for a maximum of 9 infusions.; Drug: Tocilizumab; Tocilizimab 8 mg/ actual body weight in kg IV q4 weeks
Active Comparator: Non-Black Monotherapy	Drug: Carboplatin; Carboplatin will be given AUC 6 IV q3 weeks for a maximum of 9 infusions.
Experimental: Non-Black Combination treatment	Drug: Carboplatin; Carboplatin will be given AUC 6 IV q3 weeks for a maximum of 9 infusions.; Drug: Tocilizumab; Tocilizimab 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)
Efficacy of tocilizumab 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)
Progression-free survival		through study completion (i.e. up to 2 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of carboplatin monotherapy compared to carboplatin combined with tocilizumab using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v 5.0		through study completion (i.e. up to 2 years)
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

Collaborators and Investigators

• Sponsor: Kathy Miller
• Collaborators: Genentech, Inc.
• Investigators: Principal Investigator: Kathy Miller, MD, Indiana University

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2024
• Primary Completion (Estimated): December 1, 2026
• 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 (Estimated): December 19, 2023
• Last Update Submitted That Met QC Criteria: December 13, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Breast Cancer; Phase II
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Antineoplastic Agents; Carboplatin
• 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