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

31 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug combination of Pegylated Liposomal Doxorubicin and Tamoxifen 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, often with less heart-related side effects compared to other similar drugs. PLD has been shown to improve the time before the disease progresses when combined with other drugs, which suggests it could be beneficial in combination therapies like with Tamoxifen. ^{1 2 3 4 5}

Is the combination of Tamoxifen and Pegylated Liposomal Doxorubicin safe for treating breast cancer?

Pegylated Liposomal Doxorubicin (PLD) is generally considered safe for treating breast cancer, with a lower risk of heart-related side effects compared to conventional doxorubicin. However, it can still cause side effects like myelosuppression (reduced bone marrow activity), nausea, and palmar-plantar erythrodysesthesia (hand-foot syndrome), so careful monitoring is recommended. ^{1 6 7 8 9}

What makes the drug combination of Tamoxifen and Pegylated Liposomal Doxorubicin unique for breast cancer treatment?

This treatment combines Tamoxifen, a well-established drug for hormone-sensitive breast cancer, with Pegylated Liposomal Doxorubicin, a form of chemotherapy that is designed to be less toxic and more effective by staying in the bloodstream longer. This combination aims to enhance the effectiveness of treatment by targeting cancer cells in different ways. ^{10 11 12 13 14}

What is the purpose of this trial?

This phase II trial tests how well tamoxifen and pegylated liposomal doxorubicin works in treating patients with triple negative breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic) or that has spread to nearby tissue or lymph nodes (locally advanced) and is unable to be operated on (inoperable). Tamoxifen works by blocking the effects of estrogen in the breast. This may help stop the growth of tumor cells that need estrogen to grow. Doxorubicin is in a class of medications called anthracyclines. Doxorubicin damages the cell's DNA and may kill cancer cells. It also blocks a certain enzyme needed for cell division and DNA repair. Liposomal doxorubicin is a form of the anticancer drug doxorubicin that is contained inside very tiny, fat-like particles. Liposomal doxorubicin may have fewer side effects and work better than other forms of the drug. Giving tamoxifen and pegylated liposomal doxorubicin together may work better in treating patients with metastatic or inoperable, locally advanced triple negative breast cancer than giving either of these drugs alone.

Research Team

Sheheryar Kabraji

Principal Investigator

Roswell Park Cancer Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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 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]

References

1. Australia pubmed.ncbi.nlm.nih.gov

Efficacy and toxicity of pegylated liposomal doxorubicin-based chemotherapy in early-stage breast cancer: a multicenter retrospective case-control study. [2018]

2. England 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. [2020]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Pegylated liposomal doxorubicin (Duomeisu®) monotherapy in patients with HER2-negative metastatic breast cancer heavily pretreated with anthracycline and taxanes: a single-arm, phase II study. [2023]

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

Pegylated liposomal doxorubicin plus docetaxel significantly improves time to progression without additive cardiotoxicity compared with docetaxel monotherapy in patients with advanced breast cancer previously treated with neoadjuvant-adjuvant anthracycline therapy: results from a randomized phase III study. [2022]

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

Pegylated liposomal doxorubicin (Lipo-Dox®) combined with cyclophosphamide and 5-fluorouracil is effective and safe as salvage chemotherapy in taxane-treated metastatic breast cancer: an open-label, multi-center, non-comparative phase II study. [2018]

6. United States 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. [2022]

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

Role of liposomal anthracyclines in breast cancer. [2023]

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

Pegylated liposomal doxorubicin (Caelyx®) and oral vinorelbine in first-line metastatic breast cancer patients previously treated with anthracyclines. [2018]

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

Anticancer and cardio-protective effects of liposomal doxorubicin in the treatment of breast cancer. [2020]

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

Randomized trial of cyclophosphamide, methotrexate, and fluorouracil chemotherapy added to tamoxifen as adjuvant therapy in postmenopausal women with node-positive estrogen and/or progesterone receptor-positive breast cancer: a report of the National Cancer Institute of Canada Clinical Trials Group. Breast Cancer Site Group. [2017]

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

Clinical efficacy of tamoxifen. [2022]

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

Tamoxifen. Use in treatment of metastatic breast cancer refractory to combination chemotherapy. [2019]

13. Germany pubmed.ncbi.nlm.nih.gov

Tamoxifen's impact as a preventive agent in clinical practice and an update on the STAR trial. [2019]

14. England pubmed.ncbi.nlm.nih.gov

Is long-term adjuvant treatment of breast cancer with anastrozole indicated? [2019]