Liposomal Doxorubicin + Carboplatin for Triple-negative Breast Cancer

Recruiting at 7 trial locations

Overseen By Mridula A George, MD

Age: Any Age

Sex: Female

Trial Phase: Phase 2

Sponsor: Rutgers, The State University of New Jersey

Disqualifiers: Stage III-IV cancer, Hypertension, Cardiac disease, others

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: 11

Duration: 16 weeks

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This clinical trial aims to evaluate the efficacy, safety, and exploratory measures of liposomal doxorubicin and carboplatin combination therapy in the adjuvant setting for early stage triple negative breast cancer (TNBC) patients. The primary objective is to determine the effectiveness of liposomal doxorubicin and carboplatin in reducing the risk of recurrence for early stage TNBC patients. The secondary objectives involve characterizing the safety and toxicity profile of the combination therapy. Adverse events rates will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The exploratory objectives of the study focus on evaluating changes in circulating tumor DNA (ctDNA). This measure will provide insights into the potential utility of ctDNA as a biomarker for treatment response and disease progression. By addressing these objectives, the study aims to contribute to the understanding of the benefits and risks associated with liposomal doxorubicin and carboplatin combination therapy in the adjuvant setting for early stage TNBC, potentially leading to improved treatment outcomes and patient care.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the drug Liposomal Doxorubicin + Carboplatin for Triple-negative Breast Cancer?

Research shows that pegylated liposomal doxorubicin (PLD) is effective for metastatic breast cancer and has less toxicity compared to traditional chemotherapy. Additionally, the combination of PLD and carboplatin is a standard treatment for ovarian cancer, indicating its potential effectiveness in treating other cancers like triple-negative breast cancer. ^{1 2 3 4 5}

Is the combination of Liposomal Doxorubicin and Carboplatin safe for humans?

Liposomal Doxorubicin (PLD) is generally safer than conventional doxorubicin, with less risk of heart damage and hair loss, but it can cause skin issues like hand-foot syndrome and rashes. Combining PLD with Carboplatin may reduce allergic reactions to Carboplatin, and this combination has been studied in various cancers, showing it is generally well-tolerated. ^{1 4 6 7 8}

How does the drug Liposomal Doxorubicin + Carboplatin differ from other treatments for triple-negative breast cancer?

This drug combination uses liposomal doxorubicin, which is a form of the drug doxorubicin enclosed in tiny fat-like particles, making it less toxic and potentially more effective than conventional chemotherapy. It is combined with carboplatin, which is often used in treating other cancers, and this combination is being explored for its safety and effectiveness in treating triple-negative breast cancer. ^{1 2 4 5 7}

Research Team

Mridula George, MD

Principal Investigator

Cancer Institute of New Jersey Rutgers

Eligibility Criteria

This trial is for early-stage triple-negative breast cancer patients who've had surgery, with tumors under 2.5cm and limited nodal disease. They must understand the study, have not used anthracycline chemo before, and their major organs need to function well. People with advanced cancer, uncontrolled high blood pressure or heart issues, significant medical conditions or infections like HIV/Hepatitis B/C can't join.

Inclusion Criteria

My breast cancer is early stage, triple negative, with a tumor under 2.5cm and minimal to no spread to lymph nodes.

My kidney function is within the required range.

My liver is functioning within the required limits.

Exclusion Criteria

I don't have any health issues that would stop me from joining the study.

I have a serious wound, ulcer, or bone fracture that is not healing.

I have mild to severe numbness or tingling in my hands or feet.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive liposomal doxorubicin and carboplatin every four weeks for four cycles

16 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety, effectiveness, and changes in ctDNA levels after treatment

5 years

Multiple visits at 6, 12, 18, 24 months and annually up to 5 years

Treatment Details

Interventions

• Carboplatin
• Liposomal Doxorubicin

Trial Overview The OCTANE trial tests a combination of liposomal doxorubicin and carboplatin in patients who've completed primary surgery for early-stage triple-negative breast cancer. It aims to see if this therapy reduces recurrence risk and will also explore changes in circulating tumor DNA as a potential treatment response biomarker.

Participant Groups

Group I: Liposomal doxorubicin and Carboplatin Experimental Treatment 1 Intervention

Combination of liposomal doxorubicin 30milligrams per square meter (mg/m2) and carboplatin area under the curve 5 (AUC 5), administered every four weeks for four cycles. Participants with triple-negative breast cancer (TNBC): 1. Completed breast surgery and sentinel lymph node biopsy 2. Tumor size less than2.5 and NO/ N1mi disease

Who Is Running the Clinical Trial?

Rutgers, The State University of New Jersey

Lead Sponsor

Trials

471

Recruited

81,700+

Mridula George, MD

Lead Sponsor

Trials

3

Recruited

60+

Findings from Research

In a study involving 140 women with various gynecologic cancers, the combination of pegylated liposomal doxorubicin (PLD) and carboplatin was found to be well tolerated, with manageable hematological and non-hematological toxicities.

The treatment showed promising efficacy, particularly in recurrent platinum-sensitive ovarian cancer (68% response rate) and endometrial cancer (44% response rate), while efficacy was lower in cervical/vaginal cancer (12%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination therapy with pegylated liposomal doxorubicin and carboplatin in gynecologic malignancies: a prospective phase II study of the Arbeitsgemeinschaft Gynäekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR) and Kommission Uterus (AGO-K-Ut). du Bois, A., Pfisterer, J., Burchardi, N., et al.[2018]

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]

Carboplatin combined with pegylated liposomal doxorubicin (C+PLD) offers better progression-free survival (PFS) compared to carboplatin with paclitaxel (C+P), while showing similar overall survival (OS), indicating it may be a more effective treatment option for ovarian cancer.

Pegylated liposomal doxorubicin (PLD) as a monotherapy is equally effective as other monotherapies in terms of PFS and OS, but it has a more favorable tolerability profile, with fewer severe side effects like neutropenia and gastrointestinal toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of pegylated liposomal doxorubicin in ovarian cancer: a meta-analysis of randomized clinical trials. Gibson, JM., Alzghari, S., Ahn, C., et al.[2021]

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]

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 study of 414 women with ovarian, fallopian tube, or peritoneal cancer, the combination of pegylated liposomal doxorubicin (PLD) with carboplatin significantly reduced the incidence of hypersensitivity reactions (HSR) to carboplatin, with only 2.1% of patients in the PLD-C group experiencing HSR compared to 9.0% in the non-PLD-C group.

The study demonstrated that the risk of carboplatin-induced HSR decreased dramatically with each cycle of treatment in the PLD-C group, showing rates of 2.2% at the 8th cycle compared to 39.1% in the non-PLD-C group by the 16th cycle, indicating a strong protective effect of PLD against HSR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suppressive effect upon carboplatin hypersensitivity reaction via pegylated liposomal doxorubicin combination therapy. Shimada, K., Nagao, S., Suzuki, K., et al.[2020]

In a study involving 509 women with metastatic breast cancer, pegylated liposomal doxorubicin (PLD) showed comparable progression-free survival (PFS) to standard doxorubicin, with PFS durations of 6.9 months for PLD and 7.8 months for doxorubicin.

PLD significantly reduced the risk of cardiotoxicity and other side effects such as myelosuppression, vomiting, and alopecia compared to doxorubicin, making it a safer first-line treatment option for patients with normal cardiac function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. O'Brien, ME., Wigler, N., Inbar, M., et al.[2023]

References

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

Combination therapy with pegylated liposomal doxorubicin and carboplatin in gynecologic malignancies: a prospective phase II study of the Arbeitsgemeinschaft Gynäekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR) and Kommission Uterus (AGO-K-Ut). [2018]

2. Greece pubmed.ncbi.nlm.nih.gov

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

3. England pubmed.ncbi.nlm.nih.gov

The role of pegylated liposomal doxorubicin in ovarian cancer: a meta-analysis of randomized clinical trials. [2021]

4. 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]

5. 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]

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

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

7. Japan pubmed.ncbi.nlm.nih.gov

Suppressive effect upon carboplatin hypersensitivity reaction via pegylated liposomal doxorubicin combination therapy. [2020]

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

Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. [2023]