Chemotherapy for Triple Negative Breast Cancer

Overseen By Kent F. Hoskins

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: University of Illinois at Chicago

Stay on Your Current Meds You can continue your current medications while participating

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: 16

13 Participants Needed

Trial Summary

What is the purpose of this trial?

Nonrandomized, open label, single arm, Simon's two stage MinMax design trial of neoadjuvant weekly carboplatin plus paclitaxel, followed by doxorubicin and cyclophosphamide in patients with operable Triple Negative Breast Cancer (TNBC)

Do I have to stop taking my current medications for the trial?

The trial requires that you stop taking any ovarian hormonal replacement therapy or hormonal agents like raloxifene or tamoxifen before starting the study treatment. Other medications are not specifically mentioned, so it's best to discuss your current medications with the study team.

What data supports the effectiveness of the drug combination for treating triple-negative breast cancer?

Research shows that adding carboplatin to chemotherapy improves the complete response rate in triple-negative breast cancer, meaning more patients have no signs of cancer after treatment. Additionally, combining paclitaxel with carboplatin has shown better outcomes compared to other drug combinations. ^{1 2 3 4 5}

What safety data exists for chemotherapy drugs used in treating triple negative breast cancer?

The chemotherapy drugs carboplatin, doxorubicin, and paclitaxel have been studied for safety in other cancers like ovarian cancer. Common side effects include myelosuppression (reduced bone marrow activity), hypersensitivity reactions, and fatigue. Paclitaxel can also cause neurotoxicity (nerve damage) and requires careful administration to avoid leaching from plastic containers. ^{6 7 8 9 10}

What makes the chemotherapy drug combination of Carboplatin, Cyclophosphamide, Doxorubicin, and Paclitaxel unique for treating triple-negative breast cancer?

This chemotherapy combination is unique because it includes carboplatin, which has shown increased effectiveness when added to standard anthracycline and taxane-based treatments for triple-negative breast cancer, potentially improving response rates and reducing relapse in certain patients. ^{1 3 11 12 13}

Research Team

Kent F. Hoskins

Principal Investigator

University of Illinois at Chicago

Eligibility Criteria

This trial is for women over 18 with Triple Negative Breast Cancer (TNBC) that hasn't been treated before. They must not be pregnant or breastfeeding and willing to use two birth control methods. Participants should have a life expectancy of at least 6 months, an ECOG performance status of 0-2, and adequate organ function. The cancer must be operable, and they can't have had certain treatments or conditions that would affect the trial.

Inclusion Criteria

My breast cancer is triple-negative.

I am willing to use two effective birth control methods.

Women of childbearing potential (WOCP) must not be pregnant or breast-feeding. A negative serum or urine pregnancy test is required within 14 days of study registration

Exclusion Criteria

I have mild or no nerve damage.

I haven't had major surgery in the last 2 weeks or still have major side effects from it.

I don't have any other cancers that could affect this treatment's safety or results.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy Segment 1

Participants receive weekly carboplatin and paclitaxel for up to 12 weeks, with possible dose modifications extending to 16 weeks

12-16 weeks

12 visits (in-person)

Chemotherapy Segment 2

Participants receive doxorubicin and cyclophosphamide every 14 days for 4 cycles

8 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 months

Treatment Details

Interventions

• Carboplatin
• Cyclophosphamide
• Doxorubicin
• Paclitaxel

Trial Overview The study tests weekly Carboplatin plus Paclitaxel followed by Doxorubicin and Cyclophosphamide in patients with TNBC before surgery. It's a Phase 2 nonrandomized trial where all participants receive the same treatment sequence to see how effective it is in treating their breast cancer.

Participant Groups

Group I: Single arm Experimental Treatment 4 Interventions

Low dose weekly carboplatin in combination with standard neoadjuvant chemotherapy

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?

University of Illinois at Chicago

Lead Sponsor

Trials

653

Recruited

1,574,000+

Findings from Research

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]

The combination of doxorubicin, carboplatin, and weekly paclitaxel in treating advanced epithelial ovarian cancer (EOC) shows activity, with 4 out of 12 patients achieving partial remission and 3 having stable disease.

The main toxicity observed was myelosuppression, particularly grade 4 neutropenia, but the weekly administration of paclitaxel allowed for maintaining an effective dose intensity (approximately 65 mg/m²/week) while managing side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of carboplatin, doxorubicin and weekly paclitaxel in patients with advanced ovarian carcinoma. Hess, V., Verrill, MW., Bomphray, CC., et al.[2020]

Paclitaxel is an effective treatment for treatment-refractory ovarian cancer, working by stabilizing microtubules to induce cytotoxicity, despite facing challenges like severe hypersensitivity reactions and formulation issues.

The drug is associated with significant side effects, including myelosuppression, mucositis, and neurotoxicity, which are dose-dependent, highlighting the need for careful management in clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel (taxol). Kohler, DR., Goldspiel, BR.[2019]

Paclitaxel, a novel antineoplastic drug, has shown significant effectiveness in treating advanced cancers such as ovarian, breast, non-small cell lung cancer, and head and neck cancer, with a potential to become a first-line treatment when combined with platinum for advanced ovarian cancer.

While initial hypersensitivity reactions posed challenges, current premedication strategies have reduced these side effects to less than 3%, although neutropenia remains a major dose-limiting adverse effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel (Taxol): a review of its antitumor activity in clinical studies Minireview. Hájek, R., Vorlicek, J., Slavik, M.[2015]

Paclitaxel (Taxol) is an effective chemotherapy agent for treating ovarian cancer and metastatic breast cancer, particularly in patients who have not responded to platinum-based treatments.

Nurses must be aware of the potential side effects of Paclitaxel, such as hypersensitivity reactions and peripheral neuropathy, and follow specific administration guidelines to avoid complications related to its interaction with PVC intravenous-giving sets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel (Taxol)--a guide to administration. Preston, NJ.[2019]

In a study using patient-derived xenografts from nine chemotherapy-naïve triple-negative breast cancer (TNBC) samples, docetaxel and carboplatin were found to be effective as single agents, while doxorubicin showed low activity.

The combination of docetaxel and carboplatin was more effective than either drug alone, particularly in models without hereditary mutations, highlighting the potential for optimized treatment strategies in TNBC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity of docetaxel, carboplatin, and doxorubicin in patient-derived triple-negative breast cancer xenografts. Martin, M., Ramos-Medina, R., Bernat, R., et al.[2021]

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]

References

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

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

2. Netherlands pubmed.ncbi.nlm.nih.gov

Evaluation of tolerability and efficacy of incorporating carboplatin in neoadjuvant anthracycline and taxane based therapy in a BRCA1 enriched triple-negative breast cancer cohort. [2022]

3. China pubmed.ncbi.nlm.nih.gov

Dose-dense paclitaxel plus carboplatin vs. epirubicin and cyclophosphamide with paclitaxel as adjuvant chemotherapy for high-risk triple-negative breast cancer. [2022]

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

Better pathologic complete response and relapse-free survival after carboplatin plus paclitaxel compared with epirubicin plus paclitaxel as neoadjuvant chemotherapy for locally advanced triple-negative breast cancer: a randomized phase 2 trial. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Psoralen-loaded polymeric lipid nanoparticles combined with paclitaxel for the treatment of triple-negative breast cancer. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Phase I study of carboplatin, doxorubicin and weekly paclitaxel in patients with advanced ovarian carcinoma. [2020]

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

Paclitaxel (taxol). [2019]

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

Taxane/platinum/anthracycline combination therapy in advanced epithelial ovarian cancer. [2015]

9. Slovakia pubmed.ncbi.nlm.nih.gov

Paclitaxel (Taxol): a review of its antitumor activity in clinical studies Minireview. [2015]

10. England pubmed.ncbi.nlm.nih.gov

Paclitaxel (Taxol)--a guide to administration. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Activity of docetaxel, carboplatin, and doxorubicin in patient-derived triple-negative breast cancer xenografts. [2021]

12. 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]

13. 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]