Tamoxifen + Chemotherapy for Breast Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Roswell Park Cancer Institute

Must not be taking: Chemotherapy, Immunotherapy, Biologics, others

Disqualifiers: Cardiac disease, HIV/AIDS, Hypercoagulable syndrome, 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: 30

Duration: Up to 4 years

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of combining two medications, tamoxifen and a special form of doxorubicin (pegylated liposomal doxorubicin), to treat a specific type of breast cancer known as triple negative breast cancer. This cancer has either metastasized or is inoperable. The trial targets individuals who have unsuccessfully tried at least two treatments. Participants must have a specific mutation called TP53 and meet certain health criteria. The goal is to determine if the combination of these two drugs can control the cancer more effectively than using each drug alone. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot participate if you have had chemotherapy, hormonal therapy, or certain other treatments within 4-6 weeks before the study. It's best to discuss your current medications with the study team.

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

In a previous study, pegylated liposomal doxorubicin (PLD), a form of doxorubicin, showed fewer heart-related side effects compared to the traditional version, indicating it might be safer for the heart. Another study found PLD effective in treating breast cancer, with generally manageable side effects, suggesting PLD is usually well-tolerated.

Research has shown that tamoxifen can lower the risk of breast cancer by 32% to 66%. For most patients, the benefits of tamoxifen outweigh the risks, though about 20% may experience more risks than benefits. Common side effects include hot flashes and a slightly increased risk of blood clots.

These findings suggest that using PLD and tamoxifen together is likely safe for many patients. However, individual experiences may vary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining tamoxifen with pegylated liposomal doxorubicin for breast cancer because it brings a novel approach to the treatment. Tamoxifen is a well-known medication that blocks estrogen receptors, which can help slow or stop the growth of hormone-receptor-positive breast cancer cells. Pegylated liposomal doxorubicin, on the other hand, is a form of chemotherapy that is encased in a fat bubble called a liposome, enhancing its delivery to cancer cells while reducing side effects. This combination aims to offer a powerful one-two punch: hormone therapy to block cancer growth signals and an advanced chemotherapy delivery system to kill cancer cells more effectively and with fewer side effects than traditional methods.

What evidence suggests that tamoxifen and pegylated liposomal doxorubicin might be effective for metastatic or inoperable, locally advanced triple negative breast cancer?

Research has shown that pegylated liposomal doxorubicin (PLD), a type of chemotherapy, effectively treats various stages of breast cancer, including advanced cases. PLD targets cancer cells and aims to reduce side effects. Tamoxifen blocks estrogen, which some cancer cells need to grow. In this trial, participants will receive a combination of tamoxifen and PLD, which studies have shown to be safe and moderately effective, particularly for patients with recurring breast cancer. This combination could potentially improve outcomes for those with metastatic or inoperable, locally advanced triple-negative breast cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Sheheryar Kabraji

Principal Investigator

Roswell Park Cancer Institute

Are You a Good Fit for This Trial?

This trial is for patients with triple negative breast cancer that has spread and cannot be removed by surgery. Participants should not have received certain treatments before, must have measurable disease, and acceptable organ function.

Inclusion Criteria

My tumor is HER-2 negative according to tests.

Total bilirubin ≤ 1.5 x upper limit of normal (ULN)

Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately

Exclusion Criteria

Any condition which in the Investigator's opinion deems the participant an unsuitable candidate to receive study drug

I do not have heart conditions that would prevent me from taking certain cancer treatments.

I am HIV positive or have an AIDS-related illness.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tamoxifen orally once daily and pegylated liposomal doxorubicin intravenously on day 1 of each 28-day cycle

Up to 4 years

Monthly visits for treatment administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

2 years

Follow-up at 30 days post-treatment, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Pegylated Liposomal Doxorubicin
• Tamoxifen

Trial Overview The study tests tamoxifen combined with pegylated liposomal doxorubicin in treating advanced triple negative breast cancer. Tamoxifen blocks estrogen to stop tumor growth; doxorubicin damages DNA to kill cancer cells.

How Is the Trial Designed?

Group I: Treatment (tamoxifen, pegylated liposomal doxorubicin) Experimental Treatment 7 Interventions

Patients receive tamoxifen PO QD on days 1-28 of each cycle and pegylated liposomal doxorubicin IV on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography, CT scan or MRI, tumor biopsy, and blood sample collection throughout the study.

Who Is Running the Clinical Trial?

Roswell Park Cancer Institute

Lead Sponsor

Trials

427

Recruited

40,500+

Published Research Related to This Trial

Liposomal anthracyclines, including pegylated and non-pegylated formulations of doxorubicin, have been developed to enhance the safety of traditional anthracyclines while maintaining their effectiveness against breast cancer.

These liposomal formulations are currently approved in Europe and Canada for treating metastatic breast cancer, aiming to reduce toxic side effects like cardiotoxicity, myelosuppression, and nausea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of liposomal anthracyclines in breast cancer. Lorusso, V., Manzione, L., Silvestris, N.[2023]

In a study of 50 postmenopausal women with metastatic breast cancer who had not responded to previous treatments, tamoxifen citrate led to a complete remission in 8% and a partial remission in 28% of patients, with a median response duration of eight months.

Tamoxifen was found to significantly prolong survival in responders compared to nonresponders, and the side effects of the treatment were mild, making it a favorable option for patients after other therapies have failed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tamoxifen. Use in treatment of metastatic breast cancer refractory to combination chemotherapy. Legha, SS., Buzdar, AU., Hortobagyi, GN., et al.[2019]

Doxorubicin (DOX) is an effective chemotherapy drug for breast cancer that works by damaging DNA and inducing apoptosis, but it has a risk of cardiotoxicity, limiting the total dose patients can receive.

The PEGylated liposomal formulation of DOX (L-DOX), known as Doxil® or Caelyx®, has been developed to improve cardiovascular safety and increase circulation time, although it is not yet FDA approved for metastatic breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anticancer and cardio-protective effects of liposomal doxorubicin in the treatment of breast cancer. Franco, YL., Vaidya, TR., Ait-Oudhia, S.[2020]

In a phase II study involving 35 patients with locally advanced breast cancer, the combination of paclitaxel and pegylated liposomal doxorubicin showed significant efficacy, with 71% of patients responding to treatment, including a 17% complete response rate.

The primary side effect observed was skin toxicity, particularly palmar-plantar erythrodysesthesia, but these effects were manageable, and there were no treatment-related deaths, indicating a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant chemotherapy with a combination of pegylated liposomal doxorubicin (Caelyx) and paclitaxel in locally advanced breast cancer: a phase II study by the Hellenic Cooperative Oncology Group. Gogas, H., Papadimitriou, C., Kalofonos, HP., et al.[2020]

This study analyzed over 7.5 million reports from the FDA Adverse Event Reporting System and found that conventional doxorubicin (DOX) has a higher incidence of adverse events compared to liposomal formulations, particularly in terms of myelosuppression and cardiotoxicity.

Liposomal DOX, especially the PEGylated version, showed lower reporting odds ratios for serious side effects like myelosuppression and cardiotoxicity, but a higher risk for palmar-plantar erythrodysesthesia (PPE), indicating the need for careful monitoring when using these formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the adverse event profiles of conventional and liposomal formulations of doxorubicin using the FDA adverse event reporting system. Fukuda, A., Tahara, K., Hane, Y., et al.[2022]

In a study of 27 metastatic breast cancer patients treated with pegylated liposomal doxorubicin (PLD) and vinorelbine, there were no treatment interruptions or cardiac toxicity, highlighting the cardiac safety of PLD compared to traditional doxorubicin.

The combination treatment showed a median progression-free survival of 5.3 months and an overall clinical benefit rate of 55.5%, indicating its efficacy in patients previously treated with anthracycline-based chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegylated liposomal doxorubicin (Caelyx®) and oral vinorelbine in first-line metastatic breast cancer patients previously treated with anthracyclines. Livi, L., Meattini, I., Scotti, V., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06434064

Tamoxifen and Pegylated Liposomal Doxorubicin for the ... This phase II trial tests how well tamoxifen and pegylated liposomal doxorubicin works in treating patients with triple negative breast cancer that has ...

2. withpower.com withpower.com/trial/phase-2-anatomic-stage-iv-breast-cancer-ajcc-v8-5-2024-9285f

Tamoxifen + Chemotherapy for Breast Cancer Research shows that Pegylated Liposomal Doxorubicin (PLD) is effective in treating various stages of breast cancer, including early-stage and advanced cases, ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/15022287/

Pegylated liposomal doxorubicin-efficacy in patients with ... Conclusions: Pegylated liposomal doxorubicin administered alone or in combination with tamoxifen is safe and moderately effective in patients with recurrent ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7179425/

Novel Tamoxifen Nanoformulations for Improving Breast ... This review begins with an outline of breast cancer, the current treatment options and a history of how TAM has been used as a combatant of BC.

5. tandfonline.com tandfonline.com/doi/full/10.4161/cbt.19593

Activity of pegylated liposomal doxorubicin in combination ... Activity of pegylated liposomal doxorubicin in combination with gemcitabine in triple negative breast cancer ... breast cancer: a proof-of-concept trial. Lancet ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37809186/

Cardiac Safety of Pegylated Liposomal Doxorubicin After ... PLD administration in patients with prior exposure to conventional doxorubicin appears to be safe, with limited cardiotoxicity in patients ...

7. frontiersin.org frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2024.1448037/full

Efficacy and safety of pegylated liposomal doxorubicin and ... A Phase II study reported in 2002 indicated that PLD was effective in NAC for breast cancer and its toxicity was manageable (Golshan et al., ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34307126/

Long-Term Cardiac Safety and Survival Outcomes of ... Conclusion: At 5-year follow-up, this PLD-based NAC regimen continued to be cardiac-safe and effective in a population of very high-risk breast cancer patients.

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.550

Cardiac safety and efficacy for patients with early-stage ... PLD usage may present lower incidence of cardiotoxicity than doxorubicin in the adjuvant treatment of patients with early-stage breast cancer.

10. karger.com karger.com/ort/article/47/10/484/910532/Comparison-of-the-Efficacy-Safety-and-Quality-of

Comparison of the Efficacy, Safety, and Quality of Life of ... Few retrospective studies have compared the effectiveness and safety of PLD with epirubicin as an adjuvant treatment for early breast cancer ...