Carboplatin +/- Tocilizumab for Breast Cancer

Recruiting at 3 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 is a randomized Phase II study of standard of care (SOC) chemotherapy monotherapy vs. SOC chemotherapy combined with tocilizumab in in Black and non-Black patients with metastatic triple negative or ER low breast cancer.

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 the combination of Carboplatin and Tocilizumab safe for humans?

Carboplatin is generally well-tolerated in humans, with mild side effects like nausea and low blood cell counts. Tocilizumab, used for other conditions, is also considered safe but can cause side effects like infections and liver enzyme changes. While specific safety data for the combination of Carboplatin and Tocilizumab in breast cancer is limited, both drugs have been used safely in humans for other conditions. ^{1 2 3 4 5}

What makes the drug combination of Carboplatin and Tocilizumab unique for breast cancer treatment?

The combination of Carboplatin and Tocilizumab is unique because it pairs a chemotherapy drug (Carboplatin) with an immunotherapy drug (Tocilizumab), which is typically used to treat inflammation in conditions like rheumatoid arthritis. This novel approach aims to enhance the immune response against breast cancer, potentially offering a new treatment option for patients. ^{4 5 6 7 8}

What data supports the effectiveness of the drug Carboplatin in treating breast cancer?

Research shows that Carboplatin, when used in combination with other drugs like paclitaxel, has shown promising results in treating advanced breast cancer, with response rates of 40-60% and manageable side effects. Additionally, Carboplatin has been effective in increasing complete response rates in aggressive breast cancers, especially in patients with certain genetic mutations. ^{4 5 7 9 10}

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.

Ability to provide written informed consent and HIPAA authorization

I have not had chemotherapy for cancer that has spread.

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 active or symptomatic brain or spinal cord problems.

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 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]

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]

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 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]

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 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 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]

Citations

1. England pubmed.ncbi.nlm.nih.gov

A phase II study of pembrolizumab plus carboplatin in BRCA-related metastatic breast cancer (PEMBRACA). [2023]

2. United States 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. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Phase II study of carboplatin in advanced breast cancer: preliminary results. [2013]

4. United States pubmed.ncbi.nlm.nih.gov

Paclitaxel-carboplatin combination chemotherapy in advanced breast cancer: accumulating evidence for synergy, efficacy, and safety. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

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

6. United States 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. [2022]

7. Germany 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. [2023]

8. England pubmed.ncbi.nlm.nih.gov

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

9. Netherlands pubmed.ncbi.nlm.nih.gov

A phase II study of pemetrexed and carboplatin in patients with locally advanced or metastatic breast cancer. [2015]

10. United States pubmed.ncbi.nlm.nih.gov

Paclitaxel and carboplatin as first-line chemotherapy for advanced breast cancer. [2015]