Chemotherapy for Triple Negative Breast Cancer

Recruiting at 1 trial location

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Disqualifiers: Hepatitis B, Hepatitis C, HIV, 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

Compensation: Varies

Number of Visits: 3

67 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well carboplatin and nab-paclitaxel before surgery work in treating patients with triple negative breast cancer that is inflammatory or has spread from where it started to nearby tissue or lymph nodes. Drugs used in chemotherapy, such as carboplatin and nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, since no prior therapies are allowed for the treatment of the newly diagnosed breast cancer, it's possible that you may need to stop certain medications. Please consult with the trial investigators for specific guidance.

What data supports the effectiveness of the drug combination of Carboplatin and Paclitaxel Albumin-Stabilized Nanoparticle Formulation for treating triple-negative breast cancer?

Research shows that adding carboplatin to standard chemotherapy for triple-negative breast cancer (TNBC) can be effective, with some patients experiencing no relapse. Additionally, a study found that a combination of carboplatin and nab-paclitaxel (a form of paclitaxel) was effective in early-stage TNBC, suggesting this drug combination may help treat this aggressive cancer type. ^{1 2 3 4 5}

Is the chemotherapy treatment with carboplatin and nab-paclitaxel safe for humans?

The chemotherapy treatment with carboplatin and nab-paclitaxel has been studied for safety in various cancers, including breast and lung cancer. Common side effects include neutropenia (low white blood cell count) and neuropathy (nerve damage), which can lead to treatment suspension or dose reduction. However, in trials for triple-negative breast cancer, the regimen showed low rates of severe side effects and no treatment delays. ^{1 6 7 8 9}

What makes the drug combination of Carboplatin and Paclitaxel Albumin-Stabilized Nanoparticle Formulation unique for treating triple-negative breast cancer?

This drug combination is unique because it uses nanoparticle albumin-bound paclitaxel, which may enhance the delivery and effectiveness of the treatment, and carboplatin, which is increasingly accepted for its efficacy in triple-negative breast cancer. This combination has shown promising results in clinical trials, with reduced toxicities and potential indicators of treatment response. ^{1 2 6 8 10}

Research Team

Joanne Mortimer, MD, PhD

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

This trial is for women with a specific breast cancer type called triple negative, which has spread locally or is inflammatory. They must have good heart function and normal liver tests, no prior treatments for this cancer, and agree to use contraception. It's not open to those with recent other cancers, certain infections like HIV or hepatitis B/C, neuropathy above grade 1, or if they can't follow the study rules.

Inclusion Criteria

Your creatinine levels should be less than or equal to 1.5 mg/dL, but your hospital's normal range may also be accepted.

My breast cancer is advanced but not spread to distant parts, and it's triple negative.

Women who can become pregnant must have a negative pregnancy test.

Exclusion Criteria

Pregnancy

Subjects will be excluded who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study

Any other intercurrent medical/psychological problem deemed exclusionary by the treating physician or investigators/primary investigator (PI)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Participants receive carboplatin and nab-paclitaxel intravenously. Treatment repeats every 28 days for 4 courses.

16 weeks

Weekly visits for chemotherapy administration

Surgery

Participants undergo surgery after completion of neoadjuvant chemotherapy.

Up to 6 months from initial treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

Up to 5 years

Every 3 months for 4 years, then every 6 months for 1 year

Treatment Details

Interventions

• Carboplatin
• Paclitaxel Albumin-Stabilized Nanoparticle Formulation

Trial Overview The trial tests how well carboplatin and nab-paclitaxel chemotherapy work when given before surgery in shrinking tumors of patients with advanced triple negative breast cancer. The goal is to see if these drugs can reduce tumor size enough so less normal tissue needs removal during surgery.

Participant Groups

Group I: Treatment (carboplatin and nab-paclitaxel) Experimental Treatment 3 Interventions

Patients receive carboplatin IV over 30 minutes on day 1 and paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes once weekly. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.

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?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a clinical trial involving 90 patients with triple negative breast cancer (TNBC), the optimal chemotherapy regimen combined carboplatin with standard dose-dense ACT, resulting in the lowest grade 3 or 4 toxicities and no delays or dose reductions for carboplatin.

The study identified reduced protein levels of androgen receptor and PD-L1 as potential indicators of treatment response, with Stage I patients showing a zero relapse rate, suggesting the effectiveness of the carboplatin-based regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective phase II clinical trial identifying the optimal regimen for carboplatin plus standard backbone of anthracycline and taxane-based chemotherapy in triple negative breast cancer. Hamm, C., Fifield, BA., Kay, A., et al.[2022]

In a study of 190 patients with stage I-III triple-negative breast cancer (TNBC), the neoadjuvant regimen of carboplatin and docetaxel (CbD) achieved a high pathologic complete response (pCR) rate of 55%, indicating effective tumor reduction before surgery.

The CbD regimen was well tolerated, with only 21% of patients experiencing grade 3 or 4 adverse events, suggesting it is a safe treatment option comparable to traditional chemotherapy combinations that include anthracyclines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Neoadjuvant Carboplatin plus Docetaxel in Triple-Negative Breast Cancer: Combined Analysis of Two Cohorts. Sharma, P., López-Tarruella, S., García-Saenz, JA., et al.[2022]

In a study of 40 patients with stage III/IV squamous non-small-cell lung cancer, the combination of nab-paclitaxel and a platinum agent (cisplatin or carboplatin) resulted in a high overall response rate of 62.5% and a disease control rate of 92.5%, indicating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with most adverse effects being mild to moderate (grade 1 to 2), including myelosuppression and gastrointestinal issues, suggesting that nab-paclitaxel combined with platinum agents is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical investigation of efficacy of albumin bound paclitaxel plus platinum compounds as first-line chemotherapy for stage III/IV squamous non-small cell lung cancer. Fang, Y., Wang, L., Xia, GH., et al.[2022]

In a study of patients with advanced non-small cell lung cancer receiving carboplatin and nanoparticle albumin-bound paclitaxel, 55% experienced treatment suspension, primarily due to neutropenia (65.2%) and infections (24.2%).

Baseline liver dysfunction, age 65 or older, and a performance status of 2 were identified as significant risk factors for treatment suspension, highlighting the need for careful monitoring in these patient groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of risk factors associated with carboplatin and nab-paclitaxel treatment suspension in patients with non-small cell lung cancer. Saito, Y., Takekuma, Y., Shinagawa, N., et al.[2022]

In a phase 3 trial involving 902 patients with untreated metastatic triple-negative breast cancer, the combination of atezolizumab and nab-paclitaxel significantly improved progression-free survival compared to nab-paclitaxel alone, with median survival times of 7.2 months versus 5.5 months, respectively.

The combination therapy also showed promising overall survival results, particularly in patients with PD-L1-positive tumors, where median overall survival was 25.0 months for the combination versus 15.5 months for the placebo group, indicating enhanced efficacy without new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. Schmid, P., Adams, S., Rugo, HS., et al.[2021]

References

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

A prospective phase II clinical trial identifying the optimal regimen for carboplatin plus standard backbone of anthracycline and taxane-based chemotherapy in triple negative breast cancer. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Phase II Trial of Neoadjuvant Carboplatin and Nab-Paclitaxel in Patients with Triple-Negative Breast Cancer. [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

The potential use of lapatinib-loaded human serum albumin nanoparticles in the treatment of triple-negative breast cancer. [2018]

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

Lapatinib-loaded human serum albumin nanoparticles for the prevention and treatment of triple-negative breast cancer metastasis to the brain. [2018]

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

Efficacy of Neoadjuvant Carboplatin plus Docetaxel in Triple-Negative Breast Cancer: Combined Analysis of Two Cohorts. [2022]

6. Thailand pubmed.ncbi.nlm.nih.gov

Clinical investigation of efficacy of albumin bound paclitaxel plus platinum compounds as first-line chemotherapy for stage III/IV squamous non-small cell lung cancer. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Evaluation of risk factors associated with carboplatin and nab-paclitaxel treatment suspension in patients with non-small cell lung cancer. [2022]

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

Phase II/III weekly nab-paclitaxel plus gemcitabine or carboplatin versus gemcitabine/carboplatin as first-line treatment of patients with metastatic triple-negative breast cancer (the tnAcity study): study protocol for a randomized controlled trial. [2022]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Phase II trial of weekly nab-paclitaxel and carboplatin treatment with or without trastuzumab as nonanthracycline neoadjuvant chemotherapy for locally advanced breast cancer. [2018]

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

Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. [2021]