Chemotherapy +/− Bevacizumab for Breast Cancer

Not currently recruiting at 960 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Anthracyclines, Anthracenediones, Taxanes

Disqualifiers: HER2+ cancer, Cardiovascular disease, 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: 5

Duration: 20-24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding bevacizumab (also known as Avastin) to a chemotherapy regimen can improve outcomes for people with certain types of breast cancer. It focuses on those whose cancer may have spread to the lymph nodes or is at high risk of returning. Bevacizumab may help stop cancer growth by cutting off its blood supply. This trial may suit those who have had breast cancer surgery and meet specific criteria, such as cancer that has spread to lymph nodes or certain tumor characteristics. As a Phase 3 trial, it represents the final step before FDA approval, offering patients a chance to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop taking your current medications. However, if you are taking tamoxifen or raloxifene, you must stop them before starting the trial.

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

Research has shown that the chemotherapy drugs doxorubicin hydrochloride, cyclophosphamide, and paclitaxel are commonly used and have a known safety record. These drugs attack cancer cells in different ways. They can cause side effects like nausea, hair loss, and tiredness, but these are usually manageable.

Regarding bevacizumab, studies have shown mixed results about its safety for breast cancer patients. One study found that 13.3% of patients stopped using bevacizumab due to side effects, compared to 7.2% in the group not taking it. Another study noted a small percentage (2.5%) of deaths related to treatment in patients taking bevacizumab. These risks require careful consideration.

While bevacizumab may help slow cancer growth by cutting off blood supply to tumors, it also carries some risks. Anyone considering joining a trial should consult with their healthcare provider to make an informed decision. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they explore the addition of bevacizumab, a targeted therapy, to standard chemotherapy for breast cancer. Unlike traditional treatments that mainly use chemotherapy drugs like cyclophosphamide, doxorubicin, and paclitaxel, bevacizumab works by inhibiting the growth of blood vessels that tumors need to grow. This unique mechanism may enhance the effectiveness of chemotherapy by starving the tumor of nutrients. Additionally, one arm of the study examines bevacizumab as a long-term therapy, which could provide ongoing tumor suppression beyond what's typically expected with standard care. These innovative approaches could potentially improve outcomes for patients by offering a more comprehensive attack on cancer cells.

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

This trial will compare the effects of chemotherapy alone versus chemotherapy combined with bevacizumab for breast cancer. Research has shown that adding bevacizumab to chemotherapy appears promising. One study found that bevacizumab, when used with different chemotherapy drugs, reduced the risk of cancer progression by 30%. Bevacizumab stops the growth of new blood vessels that tumors need, potentially slowing cancer spread and shrinking tumors. Participants in this trial may receive doxorubicin, cyclophosphamide, and paclitaxel, which effectively kill cancer cells and prevent their spread. Together, these treatments aim to improve outcomes for patients with high-risk breast cancer. ^{1 6 7 8 9}

Who Is on the Research Team?

Kathy D Miller

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

This trial is for adults with breast cancer that has spread to lymph nodes or is at high risk of returning. They must have had surgery between 28-84 days before starting treatment, be in good physical condition (ECOG 0-1), and have normal blood counts and organ function tests. People with HER2+ breast cancer, recent major surgeries, uncontrolled heart conditions, bleeding disorders, or who are pregnant can't join.

Inclusion Criteria

My breast cancer is not HER2 positive as determined by specific tests.

I have cancer in both breasts, but the more advanced one qualifies for the trial.

I have had a heart attack in the last 12 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive doxorubicin hydrochloride, cyclophosphamide, and paclitaxel with or without bevacizumab

20-24 weeks

Every 2 or 3 weeks for 4 courses, then every 3 weeks for 4 courses

Extended Treatment

Participants in Arm III receive additional bevacizumab monotherapy

30 weeks

Every 3 weeks for 10 courses

Follow-up

Participants are monitored for safety and effectiveness after treatment

15 years

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab
• Cyclophosphamide
• Doxorubicin Hydrochloride
• Paclitaxel

Trial Overview The study compares the effectiveness of chemotherapy drugs doxorubicin hydrochloride, cyclophosphamide, and paclitaxel with or without the antibody bevacizumab in patients after surgery. Bevacizumab may block tumor blood supply. The goal is to see which combination better prevents cancer from coming back.

How Is the Trial Designed?

Group I: Arm III (chemotherapy, bevacizumab monotherapy) Experimental Treatment 6 Interventions

Patients receive doxorubicin hydrochloride and cyclophosphamide as in arm I and bevacizumab as in arm II. Treatment repeats every 2 or 3 weeks for 4 courses. Beginning 3 weeks later, patients then receive paclitaxel as in arm I and bevacizumab as in arm II. Treatment with paclitaxel and bevacizumab repeats every 3 weeks for 4 courses. Beginning 2 months later, patients then receive bevacizumab IV over 30-90 minutes on day 1. Treatment with bevacizumab alone repeats every 3 weeks for 10 courses.

Group II: Arm II (chemotherapy, bevacizumab) Experimental Treatment 6 Interventions

Patients receive doxorubicin hydrochloride and cyclophosphamide as in arm I and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 2 or 3 weeks for 4 courses. Beginning 3 weeks later, patients then receive paclitaxel as in arm I and bevacizumab IV over 30-90 minutes on day 1. Treatment with paclitaxel and bevacizumab repeats every 3 weeks for 4 courses.

Group III: Arm I (chemotherapy, placebo) Active Control 6 Interventions

Patients receive doxorubicin hydrochloride IV, cyclophosphamide IV over 20-30 minutes, and placebo IV over 30-90 minutes on day 1. Treatment repeats every 2 or 3 weeks for 4 courses. Beginning 3 weeks later, patients then receive paclitaxel IV over 1 hour on days 1, 8, and 15 and placebo IV over 30-90 minutes on day 1. Treatment with paclitaxel and placebo repeats every 3 weeks for 4 courses.

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+

Cancer and Leukemia Group B

Collaborator

Trials

81

Recruited

118,000+

Eastern Cooperative Oncology Group

Collaborator

Trials

272

Recruited

153,000+

North Central Cancer Treatment Group

Collaborator

Trials

49

Recruited

81,100+

Published Research Related to This Trial

In a case series of 15 patients with metastatic non-squamous cell lung carcinoma, the combination of paclitaxel and bevacizumab showed a partial response rate of 44% based on CT scans and 65% based on PET scans, indicating potential efficacy in this patient population.

No major toxicity was observed in the treatment, and the median progression-free survival was 4.6 months, suggesting that this regimen is safe and may improve patient outcomes, warranting further investigation in a randomized clinical trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of paclitaxel and bevacizumab in heavily pre-treated non-small-cell lung cancer (NSCLC) patients: a case series study on 15 patients. Le Moulec, S., Hadoux, J., Gontier, E., et al.[2015]

Paclitaxel (Taxol) is an effective chemotherapy agent for treating ovarian cancer and metastatic breast cancer, particularly in patients who have not responded to platinum-based treatments.

Nurses must be aware of the potential side effects of Paclitaxel, such as hypersensitivity reactions and peripheral neuropathy, and follow specific administration guidelines to avoid complications related to its interaction with PVC intravenous-giving sets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel (Taxol)--a guide to administration. Preston, NJ.[2019]

Paeonol (Pae) has been shown to protect against doxorubicin (Dox)-induced cardiotoxicity in both rat models and primary cardiomyocytes by enhancing mitochondrial fusion and restoring cardiac function.

The protective mechanism involves the PKCε-Stat3-Mfn2 signaling pathway, where Pae activates Stat3 to promote Mfn2-mediated mitochondrial fusion, without compromising the anticancer efficacy of Dox.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paeonol protects against doxorubicin-induced cardiotoxicity by promoting Mfn2-mediated mitochondrial fusion through activating the PKCε-Stat3 pathway. Ding, M., Shi, R., Fu, F., et al.[2023]

Paclitaxel, when combined with doxorubicin, has shown a remarkable 95% objective response rate in chemotherapy-naive patients with metastatic breast cancer, indicating its high efficacy in treating this condition.

The treatment regimen demonstrated no signs of cardiac toxicity, allowing for further testing in patients with smaller tumors to potentially increase the rate of complete remission before surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future developments for paclitaxel in the treatment of breast cancer. Bonadonna, G.[2015]

In two large randomized trials, adding intravenous paclitaxel to standard doxorubicin-cyclophosphamide (AC) therapy significantly improved disease-free survival at 5 years for women with early breast cancer, with one trial also showing improved overall survival.

While paclitaxel demonstrated efficacy in neoadjuvant therapy by increasing response rates and eligibility for breast-conserving surgery, it was associated with notable grade 3-4 adverse events, primarily hematological issues like neutropenia and nausea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel: as adjuvant or neoadjuvant therapy in early breast cancer. Simpson, D., Plosker, GL.[2018]

Paclitaxel (Taxol) is a significant new chemotherapy drug for breast cancer, showing promise in both single-agent and combination treatments.

Ongoing research at Memorial Sloan-Kettering Cancer Center aims to optimize the use of paclitaxel in various treatment settings, including metastatic and adjuvant therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memorial Sloan-Kettering Cancer Center experience with paclitaxel in the treatment of breast cancer. Seidman, AD., Hudis, CA., Fennelly, D., et al.[2015]

A case study of a 39-year-old woman with recurrent breast cancer treated with bevacizumab and paclitaxel revealed a serious side effect: diverticular bleeding after the third treatment cycle.

The report suggests that bevacizumab may contribute to diverticular bleeding, highlighting the importance of assessing patient history for risk factors like diverticulitis and prior abdominal surgeries before starting this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diverticular Bleeding of the Colon during Combination Chemotherapy with Bevacizumab and Paclitaxel for Recurrent Breast Cancer. Nakayama, Y., Ito, Y., Tanabe, M., et al.[2021]

Standard treatments for breast cancer after initial chemotherapy include capecitabine, S-1, vinorelbine, irinotecan, or gemcitabine, which are effective options for managing the disease.

Newer therapies like lapatinib for trastuzumab-resistant cases and combinations like bevacizumab with taxanes show promise, highlighting the need for further research on optimal drug sequences and combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chemotherapy for breast cancer refractory to anthracycline, taxane or trastuzumab]. Ito, Y., Kobayashi, K.[2016]

Citations

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Bevacizumab and Breast Cancer: A Meta-Analysis of First- ... Results. A total of 2,695 patients were evaluated. Combining bevacizumab with different chemotherapy backbones resulted in a 30% risk reduction of PFS events ( ...

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Efficacy and Safety of Bevacizumab in Pretreated ... Efficacy and safety of bevacizumab in pretreated metastatic breast cancer: a systematic review and meta-analysis.

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Bevacizumab (Avastin®) in cancer treatment: A review of ... Development of bevacizumab, the first therapy targeting VEGF​​ In vivo studies demonstrated that bevacizumab inhibits vessel growth, induces regression of newly ...

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NCT00333775 | A Study of Bevacizumab (Avastin) in ... This study will evaluate the efficacy and safety of 2 doses of Avastin in combination with docetaxel, versus docetaxel plus placebo, in patients with ...

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the ATRACTIB phase 2 trial However, early survival estimates, before most censures, indicates a 12-month OS rate of 81.3%, which compares favorably with the observed 12- ...

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Efficacy and Safety of Bevacizumab in Pretreated ... An increased number of AEs led to study discontinuation in the bevacizumab-containing arm compared with the control arm (13.3% vs. 7.2%). TANIA was designed to ...

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Final efficacy and updated safety results of the randomized ... Five-year IDFS rates were 77% (95% CI 75–79%) with chemotherapy alone versus 80% (95% CI 77–82%) with bevacizumab. From 18 months after first study dose to ...

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FDA Says Avastin Not Safe or Effective for Patients With ... Overall, treatment-related death occurred in 2.5% of the Avastin population. In patients with breast cancer, studies failed to show statistically significant ...

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Effect of Bevacizumab in Metastatic Triple Negative Breast ... The humanized, anti-VEGF monoclonal antibody bevacizumab has been shown to increase progression-free survival (PFS) and/ or overall survival (OS) in metastatic ...