Durvalumab + Chemotherapy for Breast Cancer

Recruiting at 563 trial locations

Overseen By Sam Benjamin

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Live vaccines

Disqualifiers: Metastatic disease, Active autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 12

Duration: 20 weeks

3680 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding the immunotherapy drug durvalumab to standard chemotherapy can more effectively treat certain types of breast cancer. It focuses on patients with stage II-III hormone receptor-positive, HER2-negative breast cancer at high risk for recurrence. The study compares outcomes between patients receiving chemotherapy alone and those receiving chemotherapy with durvalumab. Individuals with this specific breast cancer type who have not yet started treatment might be suitable candidates for the trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients an opportunity to contribute to potentially groundbreaking treatment advancements.

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 any other cancer treatments like chemotherapy, immunotherapy, or hormonal therapy while participating in this study.

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

Research has shown that durvalumab, when combined with chemotherapy, is generally safe for patients with various solid cancers. Studies have found that most people tolerate this combination without serious issues. In one study, patients taking durvalumab with other treatments experienced manageable side effects and showed some improvement in their conditions.

Patients in previous trials with durvalumab and chemotherapy experienced side effects common to cancer treatments, such as fatigue and nausea. However, these side effects were often mild or moderate. These findings reassure those considering joining a trial with durvalumab and chemotherapy, suggesting a strong safety record. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for breast cancer?

Researchers are excited about the combination of durvalumab with chemotherapy for breast cancer because it introduces a new immunotherapy component, durvalumab, which is not typically part of standard chemotherapy regimens. Unlike traditional treatments that rely solely on drugs like cyclophosphamide, doxorubicin, and paclitaxel, durvalumab is a checkpoint inhibitor that works by enhancing the body’s immune response against cancer cells. This dual approach aims to boost the effectiveness of chemotherapy by allowing the immune system to better recognize and attack the tumor. By integrating immunotherapy with chemotherapy, there's potential for improved outcomes in patients who may not respond as well to conventional treatments alone.

What evidence suggests that this trial's treatments could be effective for breast cancer?

Research shows that adding durvalumab to chemotherapy can help the immune system fight cancer. In this trial, some participants will receive only chemotherapy, while others will receive chemotherapy combined with durvalumab. In other studies, when combined with other treatments, durvalumab led to a strong tumor reduction response in 79% of patients. This suggests that durvalumab might help the body defend against tumor growth and spread. For breast cancer patients with a high-risk score (MammaPrint High 2 Risk), using durvalumab with chemotherapy could potentially reduce the chance of cancer recurrence. ^{6 7 8 9 10}

Who Is on the Research Team?

Erin F Cobain

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

This trial is for adults with stage II-III hormone receptor positive, HER2 negative breast cancer who have not had prior treatment. They must be in good physical condition (Zubrod Performance Status of 0-2), have no metastatic disease, and cannot be pregnant or breastfeeding. Participants need to agree to use effective contraception and should not have a history of certain conditions like uncontrolled diabetes, active pneumonitis, or autoimmune diseases requiring recent systemic treatment.

Inclusion Criteria

As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

My breast cancer has not come back in the same area after treatment.

Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

MammaPrint Testing

Patients without a known MammaPrint Ultrahigh (MP2) score undergo MammaPrint testing on a previously-collected tissue sample

1-2 weeks

1 visit (in-person)

Treatment

Patients receive neoadjuvant chemotherapy with or without durvalumab. Paclitaxel is administered every 14 days for 6 cycles, followed by doxorubicin and cyclophosphamide every 14 days for 4 cycles.

20 weeks

10 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 10 years

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Doxorubicin
• Durvalumab
• Paclitaxel

Trial Overview

The study tests if adding Durvalumab (an immunotherapy drug) to standard chemotherapy (Paclitaxel, Cyclophosphamide, Doxorubicin) improves outcomes for patients with specific high-risk breast cancer as identified by MammaPrint testing. It's a phase III trial where participants are randomly assigned to receive either the new combination therapy or just the usual chemotherapy.

How Is the Trial Designed?

Group I: Step 2, Arm 2 (chemotherapy, durvalumab) Experimental Treatment 7 Interventions

Patients receive paclitaxel IV on days 1 and 8 of each cycle and durvalumab IV over 60 minutes on day 1 of cycles 1, 3, and 5. Treatment repeats every 14 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive doxorubicin IV and cyclophosphamide IV on day 1 of each cycle, and durvalumab IV over 60 minutes on day 1 of cycles 7 and 9. Treatment repeats every 14 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo mammography during screening (STEP 1). Patients have the option to also undergo collection of tumor tissue during initial biopsy (STEP 1) and at SOC surgery and undergo collection of blood samples throughout the study.

Group II: Step 1 (MammaPrint testing) Experimental Treatment 1 Intervention

Patients without a known MP2 score undergo MammaPrint testing on a previously-collected tissue sample. Patients with MP2 score proceed to STEP 2

Group III: Step 2, Arm 1 (chemotherapy) Active Control 6 Interventions

Patients receive paclitaxel IV on days 1 and 8 of each cycle. Treatment repeats every 14 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive doxorubicin IV and cyclophosphamide IV on day 1 of each cycle. Treatment repeats every 14 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo mammography during screening (STEP 1). Patients have the option to also undergo collection of tumor tissue during initial biopsy (STEP 1) and at SOC surgery and undergo collection of blood samples throughout the study.

Cyclophosphamide is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Cytoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in European Union as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Doxorubicin has historically been the most effective treatment for metastatic breast cancer, especially when combined with other agents like 5-fluorouracil and cyclophosphamide, leading to improved patient outcomes.

New agents such as docetaxel have shown significantly higher response rates than doxorubicin in phase III trials, and importantly, docetaxel does not carry the same risk of cardiotoxicity, making it a promising option for combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining new agents with anthracyclines in metastatic breast cancer: an overview of recent findings. Aapro, MS.[2018]

The combination therapy of doxorubicin and paclitaxel (AT) showed a superior overall response rate (47%) and longer median time to treatment failure (8.0 months) compared to single-agent therapies, although the difference in survival rates was not significant.

Both doxorubicin and paclitaxel demonstrated equivalent efficacy, with median survivals of 18.9 months for doxorubicin and 22.2 months for paclitaxel, indicating that while combination therapy may enhance response rates, it does not necessarily lead to improved survival or quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III trial of doxorubicin, paclitaxel, and the combination of doxorubicin and paclitaxel as front-line chemotherapy for metastatic breast cancer: an intergroup trial (E1193). Sledge, GW., Neuberg, D., Bernardo, P., et al.[2022]

The combination of doxorubicin (Dox) and paclitaxel has been established as a superior treatment for metastatic breast cancer, showing better response rates and longer time to disease progression compared to either drug alone, based on a phase III study.

New agents like Herceptin (trastuzumab) and DPPE are being investigated to enhance the efficacy of Dox and paclitaxel, with early results indicating they may improve response rates and prolong disease progression time when used in combination with these chemotherapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New developments in chemotherapy of advanced breast cancer. Lebwohl, DE., Canetta, R.[2016]

In a study of 47 elderly women with high-risk breast cancer, the combination of Non-Pegylated Liposomal Doxorubicin (NPL-DOX) and Cyclophosphamide followed by weekly Paclitaxel showed a low rate of cardiac toxicity over a median follow-up of 76 months, with only one case of grade 3 congestive heart failure reported.

While there was a gradual decline in left ventricular ejection fraction (LVEF) over time, it remained above 50% and did not lead to any significant clinical symptoms, indicating that the treatment is relatively safe for cardiac health in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-pegylated liposomal doxorubicin in older adjuvant early breast cancer patients: cardiac safety analysis and final results of the COLTONE study. Coltelli, L., Finale, C., Musettini, G., et al.[2023]

The combination of paclitaxel and doxorubicin has significantly improved clinical outcomes for breast cancer patients, particularly in neoadjuvant settings for locally advanced cases.

However, this combination therapy is associated with cardiac toxicity, highlighting the need for careful monitoring and future research to mitigate these risks while maintaining treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cardiac tolerance of the combination paclitaxel-anthracyclines in the context of the management of cancer of the breast]. Ferrero, JM., Magné, N., Foa, C., et al.[2015]

The combination of intravenous paclitaxel and bolus doxorubicin is an effective primary chemotherapy for stage IV breast cancer, showing significant activity with manageable side effects.

Limiting the total dose of doxorubicin to 360 mg/m2 and using granulocyte colony-stimulating factor can reduce the risk of cardiotoxicity and neutropenia, while continuing treatment with paclitaxel can enhance the chances of a complete response in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experience at the Istituto Nazionale Tumori with paclitaxel in combination with doxorubicin in women with untreated breast cancer. Gianni, L., Capri, G.[2015]

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]

Combining paclitaxel with doxorubicin has shown impressive remission rates for metastatic breast cancer, with overall rates exceeding 90% and nearly 50% achieving complete remission, especially when administered in a specific sequence.

While other combinations of paclitaxel with drugs like cisplatin and vinorelbine have shown variable results, the doxorubicin/paclitaxel combination remains the most effective and tolerable treatment option currently available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel-containing combination chemotherapy for metastatic breast cancer. Hortobagyi, GN., Ibrahim, N.[2018]

The doxorubicin-docetaxel combination is an effective first-line chemotherapy for metastatic breast cancer, achieving an overall response rate of 67% among 40 assessable patients, with 16% achieving complete remission and 51% partial remission.

The treatment was well-tolerated, with no severe cardiac or neurological toxicity reported, although 58% of patients experienced significant neutropenia, which was managed with G-CSF or GM-CSF support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-survival in responding patients with metastatic breast cancer treated with doxorubicin-docetaxel combination. A multicentre phase II trial. Mattioli, R., Lippe, P., Massacesi, C., et al.[2018]

The combination of Doxil (40 mg/m2) and vinorelbine (30 mg/m2) was found to be effective in treating metastatic breast cancer in a phase I study involving 30 women, with a recommended schedule for further testing.

This combination therapy demonstrated a favorable toxicity profile, with minimal severe side effects like neutropenia and a low incidence of significant nausea, vomiting, or hair loss, making it a promising option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of Doxil and vinorelbine in metastatic breast cancer. Burstein, HJ., Ramirez, MJ., Petros, WP., et al.[2020]

In a study involving male rats treated with doxorubicin (DOX) and paclitaxel (PTX), the addition of dexrazoxane (DZR) significantly reduced the cardiotoxic effects of DOX, demonstrating its cardioprotective properties.

The combination of DOX and PTX did not worsen the heart damage caused by DOX alone, and DZR maintained its protective effects without increasing noncardiac toxicity, suggesting a safer treatment regimen for solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardioprotection by dexrazoxane in rats treated with doxorubicin and paclitaxel. Della Torre, P., Imondi, AR., Bernardi, C., et al.[2015]

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