Carboplatin +/- Tocilizumab for Breast Cancer

Recruiting at 4 trial locations

Overseen By Xin Bryan, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Kathy Miller

Must not be taking: Methotrexate, Corticosteroids, PARP inhibitors

Disqualifiers: Active infection, HER2+ disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: up to 2 years

168 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of the chemotherapy drug carboplatin alone versus its combination with tocilizumab, a drug that may help manage inflammation. The focus is on treating individuals with metastatic triple-negative or ER-low breast cancer, which poses treatment challenges. Participants may qualify if they have this type of breast cancer that has spread and have already tried up to two treatments. The study aims to determine if adding tocilizumab can improve outcomes for these patients. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to potentially groundbreaking findings.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use methotrexate or certain corticosteroids. Hormone therapy must be stopped at least 2 weeks before joining the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that carboplatin, a common chemotherapy drug, is usually well-tolerated by patients. It often treats various cancers, including breast cancer. However, like most chemotherapy drugs, it can cause side effects such as nausea, tiredness, and low blood cell counts.

Early studies are exploring the benefits of adding tocilizumab, a drug typically used for inflammatory conditions, to carboplatin. The FDA has already approved tocilizumab for other uses, indicating its general safety. Some patients have experienced mild to moderate side effects like headaches and higher blood pressure.

In past trials, rare cases of more serious side effects, such as cytokine release syndrome (CRS), a strong immune reaction, have occurred. Overall, the combination seems well-tolerated, but monitoring for side effects is important. Always consult a healthcare provider about potential risks and benefits before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for breast cancer, which often include hormone therapy, chemotherapy, and HER2-targeted therapies, the investigational approach combines Carboplatin with Tocilizumab for a unique effect. Carboplatin is a chemotherapy drug, but Tocilizumab is an anti-inflammatory drug typically used for arthritis. The excitement around this combination stems from Tocilizumab's potential to modulate the immune system, possibly reducing inflammation and enhancing the effectiveness of Carboplatin. This dual action could offer a new therapeutic pathway that not only targets cancer cells but also addresses the tumor microenvironment, potentially improving outcomes for patients.

What evidence suggests that this trial's treatments could be effective for breast cancer?

Studies have shown that carboplatin effectively treats advanced breast cancer, achieving success rates between 20% and 35% when used alone. In this trial, some participants will receive only carboplatin, while others will receive a combination of carboplatin and tocilizumab. Research suggests that adding tocilizumab, a drug that reduces inflammation, may improve outcomes for patients with certain types of breast cancer, such as triple negative or ER-low. Tocilizumab enhances the immune system's ability to fight cancer. Early findings indicate that combining these treatments could be more effective than using carboplatin alone. ^{1 2 4 6 7}

Who Is on the Research Team?

Kathy Miller, MD

Principal Investigator

Indiana University

Are You a Good Fit for This Trial?

This trial is for adults with metastatic triple negative or ER-low breast cancer who have completed prior therapy at least a year ago. They must be in good physical condition, have adequate organ function, and not be pregnant. Participants need to consent to biopsies and agree to use effective contraception. Those with treated brain metastases may join if stable.

Inclusion Criteria

I agree to a biopsy for this study.

I have not had chemotherapy for cancer that has spread.

Ability to provide written informed consent and HIPAA authorization

Exclusion Criteria

My cancer is HER2 positive based on specific test results.

I have not started hormone therapy in the last 2 weeks.

I have not had radiation therapy in the last 2 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either SOC chemotherapy monotherapy or SOC chemotherapy combined with tocilizumab

up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Tocilizumab

Trial Overview

The study compares carboplatin alone versus carboplatin combined with tocilizumab in patients with certain types of advanced breast cancer. It's randomized, meaning participants are assigned to one of the two treatment groups by chance.

How Is the Trial Designed?

Group I: Non-Black Combination treatment Experimental Treatment 2 Interventions

Group II: Black Combination treatment Experimental Treatment 2 Interventions

Group III: Black Monotherapy Active Control 1 Intervention

Group IV: Non-Black Monotherapy Active Control 1 Intervention

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Kathy Miller

Lead Sponsor

Trials

8

Recruited

300+

Breast Cancer Research Foundation

Collaborator

Trials

79

Recruited

40,500+

Susan G Koman for the Cure Breast Cancer Foundation

Collaborator

Trials

1

Recruited

170+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Published Research Related to This Trial

In a phase II study involving 22 patients with BRCA1/2-related metastatic breast cancer, the combination of pembrolizumab and carboplatin showed an overall response rate (ORR) of 43% and a disease control rate (DCR) of 76%, indicating some level of efficacy, particularly in luminal tumors.

Despite the promising results, the study did not meet its primary aim of achieving an ORR of 70%, leading to its termination; however, the safety profile was acceptable with only 22.7% of patients experiencing grade ≥3 adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of pembrolizumab plus carboplatin in BRCA-related metastatic breast cancer (PEMBRACA). Cortesi, L., Venturelli, M., Cortesi, G., et al.[2023]

In a phase II study involving 50 patients with locally advanced or metastatic breast cancer, the combination of pemetrexed and carboplatin showed a promising overall response rate of 54%, with a median response duration of 11.1 months.

The treatment was associated with manageable safety concerns, primarily hematologic toxicities, including grade 3/4 neutropenia in 58% of patients, but no severe non-hematologic toxicities were reported, indicating an acceptable safety profile for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of pemetrexed and carboplatin in patients with locally advanced or metastatic breast cancer. Garin, A., Manikhas, A., Biakhov, M., et al.[2015]

In a phase II study involving 66 patients with advanced breast cancer, the combination of paclitaxel and carboplatin resulted in a total response rate of 53%, with 12% achieving a complete response and 41% a partial response.

The treatment was generally well-tolerated, with manageable toxicities, allowing for outpatient administration, and a median time to progression of 8.9 months, indicating significant activity against advanced breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel and carboplatin as first-line chemotherapy for advanced breast cancer. Fountzilas, G., Athanassiades, A., Papadimitriou, V., et al.[2015]

In a study of 114 dogs treated with carboplatin, a non-haematological toxicity rate of 19.3% was observed, indicating that while carboplatin is generally well-tolerated, some dogs can experience side effects.

This case report highlights the first instance of cutaneous delayed-hypersensitivity to carboplatin in a dog, which was successfully managed with antihistamines and adjustments to future treatments, ensuring no further reactions occurred.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Probable cutaneous hypersensitivity to carboplatin single-agent chemotherapy in a dog. Lanore, D., Sayag, D.[2013]

In a study of 245 treatment-naïve Chinese patients with stage IV non-squamous non-small-cell lung cancer, the addition of atezolizumab to carboplatin and nab-paclitaxel significantly improved progression-free survival (12.98 months vs. 10.89 months) and overall survival (38.04 months vs. 33.59 months) compared to chemotherapy alone.

However, this combination therapy also led to a higher incidence of grade ≥3 adverse events, with 84% of patients in the atezolizumab group experiencing severe side effects, highlighting the need to balance efficacy with safety in treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab plus carboplatin and nab-paclitaxel versus carboplatin and nab-paclitaxel as treatments for Chinese, treatment-naïve, stage IV, non-squamous, non-small-cell lung cancer patients: A retrospective analysis. Chen, Y., Kang, S., Yan, M.[2022]

The combination of paclitaxel and carboplatin (PC) has shown promising response rates of 40-60% and median survival times of 12-20 months in patients with advanced breast cancer, making it a viable alternative to traditional anthracycline-based treatments.

In a randomized phase III trial, PC demonstrated equivalent efficacy and manageable toxicity compared to the standard treatment of epirubicin/paclitaxel, suggesting it could be a safer option for patients with prior anthracycline exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel-carboplatin combination chemotherapy in advanced breast cancer: accumulating evidence for synergy, efficacy, and safety. Pentheroudakis, G., Razis, E., Athanassiadis, A., et al.[2018]

Platinum analogs, such as carboplatin and cisplatin, show significant antitumor activity in aggressive breast cancer types, particularly in HER2-positive and BRCA1 mutation carriers, enhancing treatment effectiveness when combined with other therapies.

Neoadjuvant treatment with carboplatin increases the pathologic complete response (pCR) rates in both BRCA-mutated and sporadic triple-negative breast cancer, indicating its potential as a key component in chemotherapy regimens, although optimal dosing and scheduling still need to be clarified through ongoing trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing the role of platinum agents in aggressive breast cancers. Sikov, WM.[2022]

In a study of 124 patients with treatment-naïve, metastatic nonsquamous PD-L1-positive non-small cell lung cancer, the combination of atezolizumab with carboplatin and nab-paclitaxel showed significantly improved overall survival (19.9 months) and progression-free survival (8.5 months) compared to carboplatin and nab-paclitaxel alone (14.8 months and 5.1 months, respectively).

While the combination therapy had a higher incidence of manageable adverse events like neutropenia and anemia, it still demonstrated a tolerable safety profile, suggesting it could be an effective first-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin and nab-paclitaxel chemotherapy with or without atezolizumab as front-line management for treatment-naïve metastatic nonsquamous non-small cell lung cancer with PD-L1 staining: a retrospective study. Xu, B., Cheng, H., Li, K., et al.[2023]

In a trial involving patients with advanced breast cancer who had prior chemotherapy, carboplatin showed no objective responses, indicating limited efficacy in this group.

In contrast, preliminary results from an ongoing trial with patients who had no prior chemotherapy exposure showed a 32% overall response rate, suggesting that carboplatin may be more effective in treatment-naive patients, with mild toxicity reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of carboplatin in advanced breast cancer: preliminary results. Martin, M., Diaz-Rubio, E., Casado, A., et al.[2013]

In a study of 55 women with resectable and locally advanced breast cancer, neoadjuvant treatment with carboplatin and weekly paclitaxel, with or without trastuzumab, resulted in a high pathologic complete response (pCR) rate of 45%, particularly in patients with HER2-positive tumors (76% pCR rate).

The treatment was well tolerated, with no severe side effects like febrile neutropenia, and showed promising recurrence-free survival (RFS) rates of 88.7% at a median follow-up of 28 months, suggesting the regimen's effectiveness and safety in high-risk breast cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frequent pathologic complete responses in aggressive stages II to III breast cancers with every-4-week carboplatin and weekly paclitaxel with or without trastuzumab: a Brown University Oncology Group Study. Sikov, WM., Dizon, DS., Strenger, R., et al.[2022]

Citations

1.

research-studies.allinforhealth.info

research-studies.allinforhealth.info/us/en/listing/12862/phase-ii-trial-of-13/

Phase II Trial of Carboplatin +/- Tocilizumab for | Clinical

This study investigates the effects of an investigational medication alone compared to the same medication combined with tocilizumab in patients ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11688104/

First-line carboplatin-based chemotherapy may be ...

This study aimed to evaluate the efficacy, survival and safety of carboplatin based first-line chemotherapy in advanced breast cancer of HER2- ...

3.

trialfinder.panfoundation.org

trialfinder.panfoundation.org/en-US/trial/listing/444738

Tocilizumab for Triple Negative and ER-low Breast Cancers

This is a randomized Phase II study of standard of care (SOC) chemotherapy monotherapy vs. SOC chemotherapy combined with tocilizumab in in ...

4.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/15477636/

Carboplatin in combination therapy for metastatic breast cancer

Single-agent carboplatin is active in patients with previously untreated metastatic breast cancer, producing response rates of 20%-35%.

5.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03424005

NCT03424005 | A Study Evaluating the Efficacy and Safety ...

A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic or Locally Advanced Breast Cancer (Morpheus-panBC).

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11179535/

Cytokine Release Syndrome in a Patient With Metastatic ...

We report a case of grade 4 CRS that occurred after hypofractionated RT in a patient with metastatic triple-negative breast cancer, who had previously ...

7.

biomarkerres.biomedcentral.com

biomarkerres.biomedcentral.com/articles/10.1186/s40364-021-00312-w/tables/2

Antiangiogenic therapy reverses the immunosuppressive ...

Table 2 Currently enrolled clinical studies of antiangiogenic immunotherapy combinations for breast cancer (data source: clinicalTrials.gov, Oct 2020) ; 4.