Liposomal Doxorubicin + Carboplatin for Triple-negative Breast Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, liposomal doxorubicin and carboplatin, to determine if they can reduce the recurrence of early-stage triple-negative breast cancer, which does not respond to hormone therapy. Researchers aim to identify any side effects and assess how the treatment affects blood markers related to cancer. Suitable candidates for this trial include those who have completed surgery for early-stage triple-negative breast cancer, with a tumor size smaller than 2.5 cm, and no serious heart or liver issues. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of liposomal doxorubicin and carboplatin is generally well-tolerated. A study on patients with advanced triple-negative breast cancer (TNBC) found that many responded well to the treatment with few side effects. Another review noted that liposomal doxorubicin caused very few heart-related issues, a common concern with its regular form. This suggests that the treatment may be safer for the heart. Overall, evidence indicates that this combination treatment is relatively safe, with few serious side effects reported in previous studies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining liposomal doxorubicin with carboplatin for treating triple-negative breast cancer because it could offer a more targeted approach. Unlike traditional chemotherapy, which can affect both cancerous and healthy cells, liposomal doxorubicin is encapsulated in liposomes, allowing it to deliver the drug more directly to cancer cells while minimizing damage to normal cells. This can potentially reduce side effects and improve the tolerability of the treatment. Additionally, carboplatin is used to enhance the effectiveness of this combination by interfering with the DNA repair of cancer cells, making it a promising strategy for tackling this aggressive form of breast cancer.

What evidence suggests that liposomal doxorubicin and carboplatin could be effective for early stage triple-negative breast cancer?

Research shows that a combination of liposomal doxorubicin and carboplatin might effectively treat early-stage triple-negative breast cancer (TNBC). In this trial, participants will receive this combination treatment. Previous studies found that this combination works well and has few side effects in patients with advanced TNBC. Additionally, platinum-based treatments like carboplatin have improved long-term outcomes, such as disease-free survival and overall survival, in those with early TNBC. Liposomal doxorubicin targets the tumor directly, while carboplatin enhances the treatment's effectiveness. These findings suggest potential benefits for patients with early-stage TNBC. ^{1 2 4 6 7}

Who Is on the Research Team?

Mridula George, MD

Principal Investigator

Cancer Institute of New Jersey Rutgers

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05949021

OCTANE: Adjuvant Liposomal Doxorubicin and ... This clinical trial aims to evaluate the efficacy, safety, and exploratory measures of liposomal doxorubicin and carboplatin combination therapy in the ...

2. aacrjournals.org aacrjournals.org/cancerres/article/82/4_Supplement/P2-12-15/680854/Abstract-P2-12-15-Neoadjuvant-liposomal

Abstract P2-12-15: Neoadjuvant liposomal doxorubicin and ... Our prior trial combining carboplatin (CAR) with liposomal doxorubicin (DOX) for metastatic TNBC showed good response rates with minimal side effects.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10959715/

Platinum chemotherapy for early triple-negative breast cancer Platinum-based chemotherapy using carboplatin in the adjuvant or neoadjuvant setting improves long-term outcomes of DFS and OS in early TNBC.

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-06870

Liposomal Doxorubicin and Carboplatin for the Treatment ... Giving liposomal doxorubicin and carboplatin in combination may be effective at treating patients with early stage triple negative breast cancer.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02315196

Pegylated Liposomal Doxorubicin Hydrochloride and ... Giving pegylated liposomal doxorubicin hydrochloride and carboplatin followed by surgery and paclitaxel may be an effective treatment for breast cancer.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6138971/

Anticancer and cardio-protective effects of liposomal ... A review of available Phase II and III trials in BC patients has demonstrated that the use of L-DOX generally causes very little cardiotoxicity.

7. bmjoncology.bmj.com bmjoncology.bmj.com/content/4/1/e000573

Thirty years from FDA approval of pegylated liposomal ... 107 Patients with triple-negative breast cancer who were treated with doxorubicin showed an enhancement in T-cell cytotoxicity pathways and ...