Chemotherapy for Triple Negative Breast Cancer

Overseen By Clinical Trials Office

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Rutgers, The State University of New Jersey

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Pregnancy, Metastatic disease, Heart failure, 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: Unknown

62 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot receive other treatments for breast cancer while participating in this trial.

What data supports the effectiveness of the drug pegylated liposomal doxorubicin in treating triple-negative breast cancer?

Research shows that pegylated liposomal doxorubicin is effective in treating metastatic breast cancer and has a favorable safety profile compared to conventional chemotherapy. It is also used successfully in combination with carboplatin for ovarian cancer, suggesting potential benefits for similar combinations in triple-negative breast cancer. ^{1 2 3 4 5}

Is chemotherapy for triple-negative breast cancer generally safe?

Chemotherapy drugs like pegylated liposomal doxorubicin (PLD) and paclitaxel have been used in various cancer treatments and are generally considered safe, though they can cause side effects. PLD has less heart-related toxicity compared to other similar drugs, but it can cause skin issues like hand-foot syndrome. Paclitaxel combined with PLD has shown moderate toxicity, with some serious side effects in a small number of patients. ^{1 2 6 7 8}

What makes the drug combination of Carboplatin and Pegylated Liposomal Doxorubicin unique for treating triple-negative breast cancer?

This drug combination is unique because Pegylated Liposomal Doxorubicin (PLD) offers reduced heart-related side effects compared to traditional chemotherapy drugs, making it safer for patients who have previously received similar treatments. Additionally, there is no standard chemotherapy for triple-negative breast cancer, so this combination provides a promising option with a favorable safety profile. ^{1 2 5 6 9}

What is the purpose of this trial?

This phase II trial studies how well pegylated liposomal doxorubicin hydrochloride and carboplatin followed by surgery and paclitaxel work in treating patients with stage II-III breast cancer that does not have estrogen receptors, progesterone receptors, or large amounts of human epidermal growth factor receptor 2 (HER2)/neu protein (triple negative). Drugs used in chemotherapy, such as pegylated liposomal doxorubicin hydrochloride, carboplatin, and 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 pegylated liposomal doxorubicin hydrochloride and carboplatin before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving pegylated liposomal doxorubicin hydrochloride and carboplatin followed by surgery and paclitaxel may be an effective treatment for breast cancer.

Research Team

Kim M. Hirshfield

Principal Investigator

Rutgers Cancer Institute of New Jersey

Eligibility Criteria

This trial is for women with previously untreated stage II-III triple-negative breast cancer who are expected to live more than a year and can undergo surgery. They must have good performance status, satisfactory blood counts, normal heart function, and agree to use contraception. Excluded are those with certain cardiac conditions, serious disorders, inflammatory breast cancer, severe lung or nervous system issues, history of major organ transplant or need for immunosuppression.

Inclusion Criteria

I do not have any non-healing wounds or skin issues.

I have stage II-III breast cancer that is ER, PgR, and HER2 negative.

I am eligible for surgery to treat my breast cancer.

Exclusion Criteria

I have a heart condition.

My cancer has spread to other parts of my body.

I have been diagnosed with inflammatory breast cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Patients receive pegylated liposomal doxorubicin hydrochloride and carboplatin intravenously every 28 days for 4 courses

16 weeks

Surgery

Patients undergo definitive surgery at the discretion of the treating physician

Adjuvant Treatment

Patients receive paclitaxel intravenously once weekly for 12 weeks

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 20 years

Treatment Details

Interventions

• Carboplatin
• Paclitaxel
• Pegylated Liposomal Doxorubicin Hydrochloride
• Therapeutic Conventional Surgery

Trial Overview The study tests if pegylated liposomal doxorubicin hydrochloride and carboplatin chemotherapy before surgery followed by paclitaxel after surgery can effectively treat patients with triple-negative breast cancer. The treatment aims to shrink tumors pre-surgery and eliminate remaining cells post-surgery.

Participant Groups

Group I: Treatment (doxil, carboplatin, surgery, paclitaxel) Experimental Treatment 7 Interventions

NEOADJUVANT: Patients receive pegylated liposomal doxorubicin hydrochloride\* IV over 90 minutes and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. ADJUVANT: Patients undergo definitive surgery at the discretion of the treating physician. Patients then receive paclitaxel IV over 60 minutes once weekly for 12 weeks in the absence of disease progression or unacceptable toxicity. \*NOTE: If there is a shortage of pegylated liposomal doxorubicin hydrochloride, patients receive epirubicin hydrochloride IV over 15-20 minutes on day 1.

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?

Rutgers, The State University of New Jersey

Lead Sponsor

Trials

471

Recruited

81,700+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Rutgers Cancer Institute of New Jersey

Collaborator

Trials

72

Recruited

22,200+

Findings from Research

In a study of 162 patients with stages I-III Triple-negative breast cancer (TNBC), pegylated liposomal doxorubicin (PLD) showed similar overall survival (OS) and relapse-free survival (RFS) rates compared to conventional chemotherapy, indicating its efficacy as an alternative treatment.

PLD-based chemotherapy resulted in a lower incidence of severe neutropenia (25% vs. 41.6%) but a higher incidence of hand-foot syndrome (16.3% vs. 4.4%), suggesting a different safety profile compared to traditional anthracycline treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of pegylated liposomal doxorubicin-based adjuvant chemotherapy in patients with stage I-III triple-negative breast cancer. Lien, MY., Liu, LC., Wang, HC., et al.[2018]

The combination of non-pegylated liposomal doxorubicin and carboplatin showed a disease control rate of 30% at 12 months in 87 patients with platinum-sensitive recurrent ovarian cancer, indicating its potential efficacy as a treatment option.

The treatment had an acceptable safety profile, with significant side effects like grade 3-4 neutropenia occurring in 17% of patients, and the use of G-CSF support was associated with better outcomes, highlighting the importance of managing side effects in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-pegylated liposomal doxorubicin (NPLD, Myocet®) + carboplatin in patients with platinum sensitive ovarian cancers: A ARCAGY-GINECO phase IB-II trial. Romeo, C., Joly, F., Ray-Coquard, I., et al.[2019]

In a study of 81 late-relapsing advanced ovarian cancer patients, the combination of pegylated liposomal doxorubicin (PLD) and carboplatin resulted in a high objective response rate of 65.4%, indicating effective treatment.

The treatment was well-tolerated, with manageable side effects; most adverse reactions were hematological, and no cases of cardiotoxicity or treatment-related deaths were reported, supporting its safety as a second-line therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegylated liposomal doxorubicin and carboplatin in late-relapsing ovarian cancer: a GINECO group phase II trial. Weber, B., Lortholary, A., Mayer, F., et al.[2018]

Pegylated liposomal doxorubicin (Caelyx®/Doxil®) is an improved formulation of conventional doxorubicin that significantly reduces cardiotoxicity and enhances pharmacokinetics.

Clinical trials demonstrate that pegylated liposomal doxorubicin is effective in treating several cancers, including metastatic breast cancer and ovarian cancer, while maintaining a favorable safety profile compared to traditional chemotherapy agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegylated liposomal doxorubicin: a guide to its use in various malignancies. Lyseng-Williamson, KA., Duggan, ST., Keating, GM.[2018]

Pegylated liposomal doxorubicin (PLD) is an effective treatment for ovarian cancer that significantly reduces the risk of cardiotoxicity and other common side effects like nausea and hair loss, thanks to its unique formulation.

However, PLD is associated with dose-limiting cutaneous toxicities, including hand-foot syndrome, follicular rash, intertrigo-like eruptions, and hyperpigmentation, which are important considerations for patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegylated liposomal doxorubicin (PLD): enhanced skin toxicity in areas of vitiligo. Yuan, Y., Orlow, SJ., Curtin, J., et al.[2022]

In a phase II study involving 34 patients with metastatic breast cancer, the combination of paclitaxel and liposomal doxorubicin was effective in 73% of patients, showing a high response rate with 7 complete and 18 partial responses.

The treatment had a moderate toxicity profile, with only a small number of severe side effects reported, including 2 toxic deaths (6%), indicating that while effective, careful monitoring for serious adverse effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First line therapy with paclitaxel (Taxol) and pegylated liposomal doxorubicin (Caelyx) in patients with metastatic breast cancer: a multicentre phase II study. Vorobiof, DA., Rapoport, BL., Chasen, MR., et al.[2015]

References

1. Greece pubmed.ncbi.nlm.nih.gov

Safety and efficacy of pegylated liposomal doxorubicin-based adjuvant chemotherapy in patients with stage I-III triple-negative breast cancer. [2018]

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

Non-pegylated liposomal doxorubicin (NPLD, Myocet®) + carboplatin in patients with platinum sensitive ovarian cancers: A ARCAGY-GINECO phase IB-II trial. [2019]

3. Greece pubmed.ncbi.nlm.nih.gov

Pegylated liposomal doxorubicin and carboplatin in late-relapsing ovarian cancer: a GINECO group phase II trial. [2018]

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

Pegylated liposomal doxorubicin: a review of its use in metastatic breast cancer, ovarian cancer, multiple myeloma and AIDS-related Kaposi's sarcoma. [2022]

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

Pegylated liposomal doxorubicin: a guide to its use in various malignancies. [2018]

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

Efficacy and toxicity profile of pegylated liposomal doxorubicin (Caelyx) in patients with advanced breast cancer. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Pegylated liposomal doxorubicin (PLD): enhanced skin toxicity in areas of vitiligo. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

First line therapy with paclitaxel (Taxol) and pegylated liposomal doxorubicin (Caelyx) in patients with metastatic breast cancer: a multicentre phase II study. [2015]

9. 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]