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

• Sponsor: Kathy Miller (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05846789
• Collaborator: Genentech, Inc. (Industry)
• Enrollment: 168
• Locations: 3
• Arms: 4
• Anticipated Duration (Months): 24
• Patients Per Site: 56
• Patients Per Site Per Month: 2.3

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Breast Cancer; Triple Negative Breast Cancer; Estrogen-receptor-low Breast Cancer	Drug: Carboplatin; Drug: Tocilizumab	Phase 2

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 168 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Patients are stratified by either Black or non-Black (race-based cohort) and are then randomized 1:1 to either the monotherapy or combination arm. 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 for a total of 168 subjects across all 4 arms.Patients are stratified by either Black or non-Black (race-based cohort) and are then randomized 1:1 to either the monotherapy or combination arm. 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 for a total of 168 subjects across all 4 arms.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Carboplatin +/- Tocilizumab as Initial Therapy for Metastatic Triple Negative and ER-low Breast Cancers
• Anticipated Study Start Date: Jun 1, 2023
• Anticipated Primary Completion Date: Jun 1, 2025
• Anticipated Study Completion Date: Jun 1, 2025

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Overall response rate [through study completion (i.e. up to 2 years)]

2. Efficacy of tocilizumab in Black and non-Black patients [through study completion (i.e. up to 2 years)]

   efficacy defined as using the difference in difference approach across race based cohorts

3. Progression-free survival [through study completion (i.e. up to 2 years)]

Secondary Outcome Measures

1. 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)]

2. Evaluate the differences in inflammatory pathways between Black and non-Black patients [Baseline]

   Tumor PZP, IL-6, and phosphoSTAT3

3. Evaluate the impact of Duffy genotype on efficacy in Black patients [Baseline]

   Tumor PZP, IL-6, and phosphoSTAT3 between Duffy-null, Duffy-heterozygous, and Duffy-wild type

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

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

1. Measurable disease based on RECIST 1.1 criteria.

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

1. 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.

1. ECOG PS 0 or 1

2. 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.

3. Adequate organ function as indicated by:

4. Total bilirubin < ULN (except in patients with documented Gilbert's disease, who must have a total bilirubin < 3.0 mg/dL)

5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 5.0 x ULN

6. Creatinine clearance of > 50 mL/min using the Cockcroft-Gault formula

7. Absolute neutrophil count (ANC) > 1.5 K/mm3

8. Platelets > 100 K/ mm3

9. 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:

11. Has undergone a hysterectomy or bilateral oophorectomy; or

12. Has been naturally amenorrheic for at least 24 consecutive months.

13. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	IU Health Joe and Shelly Schwarz Cancer Center	Carmel	Indiana	United States	46032
2	Indiana University Melvin and Bren Simon Comprehensive Cancer Center	Indianapolis	Indiana	United States	46202
3	Sidney and Lois Eskenazi Hospital	Indianapolis	Indiana	United States	46202

Sponsors and Collaborators

• Kathy Miller
• Genentech, Inc.

Investigators

• Principal Investigator: Kathy Miller, MD, Indiana University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Kathy Miller, Ballvé-Lantero Professor of Medicine, Indiana University
• ClinicalTrials.gov Identifier: NCT05846789
• Other Study ID Numbers: CTO-IUSCCC-0817
• First Posted: May 6, 2023
• Last Update Posted: May 6, 2023
• Last Verified: Apr 1, 2023

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Kathy Miller, Ballvé-Lantero Professor of Medicine, Indiana University: Breast Cancer; Phase II
• Additional relevant MeSH terms: Breast Neoplasms; Triple Negative Breast Neoplasms; Carboplatin

Study Results

No Results Posted as of May 6, 2023