What is the mechanism of action of this treatment?

Adjuvant chemotherapy (ACT) for breast cancer typically involves cytotoxic agents that target rapidly dividing cancer cells. These agents, such as anthracyclines (e.g., doxorubicin) and taxanes (e.g., paclitaxel), work by interfering with DNA replication and cell division, leading to cancer cell death. This is crucial for breast cancer patients as it helps to reduce the risk of recurrence and improve survival rates by eliminating residual cancer cells that may remain after surgery. Understanding these mechanisms allows for better treatment planning and management of potential side effects, ultimately improving patient outcomes.

What side effects are associated with this type of intervention?

Common treatments for breast cancer, particularly adjuvant chemotherapy (ACT) involving cytotoxic agents like paclitaxel, carboplatin, and doxorubicin, are associated with several side effects. These include hematologic toxicities such as neutropenia, anemia, and thrombocytopenia, which increase the risk of infections and bleeding. Gastrointestinal issues like nausea, vomiting, and diarrhea are also common. Neuropathy, characterized by numbness and tingling in the extremities, is frequently observed, especially with paclitaxel. Endocrine therapies, such as tamoxifen and aromatase inhibitors, can lead to hot flashes, bone density loss, and an increased risk of cardiovascular events. Fatigue, alopecia (hair loss), and mucositis (inflammation of the mucous membranes) are additional side effects that patients may experience.

What prior FDA approvals exist?

The FDA has approved several cytotoxic agents for the treatment of breast cancer, particularly in the adjuvant setting. Notable approvals include combinations like doxorubicin and cyclophosphamide, often followed by paclitaxel or docetaxel. These agents target rapidly dividing cancer cells and have been foundational in breast cancer chemotherapy. Additionally, drugs like capecitabine and lapatinib have been approved for use in combination therapies for advanced or metastatic breast cancer, providing options for patients who have progressed on initial treatments.

What other types of research exist?

Promising novel alternatives to Adjuvant Chemotherapy (ACT) for breast cancer patients include: 1) Targeted therapies such as trastuzumab deruxtecan and pertuzumab, particularly for HER2-positive breast cancer. 2) Immunotherapies, including checkpoint inhibitors like pembrolizumab, which have shown efficacy in triple-negative breast cancer. 3) PARP inhibitors like olaparib for patients with BRCA mutations. These alternatives offer targeted mechanisms of action with potentially fewer side effects compared to traditional cytotoxic chemotherapy.

← Back to Search

Hormone Therapy

Chemotherapy + Hormone Therapy for Breast Cancer (OFSET Trial)

Phase 3

Recruiting

Research Sponsored by NRG Oncology

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patient must have undergone axillary staging with sentinel node biopsy (SNB), targeted axillary dissection (TAD), or axillary lymph node dissection (ALND).

The tumor must be ER and/or PgR-positive (progesterone receptor) by current ASCO/CAP guidelines based on local testing results.

Must not have

Non-epithelial breast malignancies such as sarcoma or lymphoma.

Patients with evidence of chronic hepatitis B virus (HBV) infection are ineligible unless the HBV viral load is undetectable on suppressive therapy.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up measured at one year after randomization

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial is testing if adding additional cancer-fighting drugs to treatments that stop certain body functions is better than just using the treatments that stop those functions alone. It targets younger women with early-stage breast cancer who have a higher risk of dying from the disease. The treatment works by stopping certain body functions and using drugs to kill cancer cells.

Who is the study for?

This trial is for premenopausal women at least 18 years old with early-stage, ER-positive/HER2-negative breast cancer and a low to intermediate recurrence score. They must have had surgery for breast cancer within the last 16 weeks and be eligible for radiation therapy. Women can't join if they are pregnant, breastfeeding, have severe heart issues, other non-breast cancers that could affect the study's safety or results, or any metastatic disease.

What is being tested?

The trial is testing if adding adjuvant chemotherapy to ovarian function suppression plus endocrine therapy improves survival without invasive breast cancer returning in patients with certain types of early-stage breast cancer compared to just ovarian function suppression plus endocrine therapy.

What are the potential side effects?

Potential side effects include those common to chemotherapy such as nausea, hair loss, fatigue and increased risk of infection; and from hormonal therapies like hot flashes, joint pain and bone thinning. The exact side effects will depend on the specific drugs used.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I have had a procedure to check for cancer in my underarm lymph nodes.

Select...

My tumor is positive for estrogen or progesterone receptors.

Select...

I am premenopausal with functioning ovaries.

Select...

My tumor is not HER2 positive according to specific guidelines.

Select...

I am a woman aged 18 or older.

Select...

My surgery removed all visible cancer from the breast.

Select...

My lumpectomy margins were clear of cancer and DCIS.

Select...

I can take care of myself but might not be able to do heavy physical work.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

My breast cancer is not the common type; it's a rare form like sarcoma or lymphoma.

Select...

I have chronic hepatitis B but it's undetectable with my current treatment.

Select...

My cancer has spread to other parts of my body, confirmed by tests.

Select...

My breast cancer is at an advanced stage or is inflammatory.

Select...

I have not received any treatment for my current breast cancer diagnosis before joining.

Select...

I have had breast cancer in either the same or the opposite breast before.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ time from randomization for duration of trial, 11 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~time from randomization for duration of trial, 11 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and time from randomization for duration of trial, 11 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Invasive breast cancer-free survival (IBCFS)

Secondary study objectives

Breast cancer-free interval (BCFI)

Distant recurrence-free interval (DRFI)

Invasive disease-free survival (IDFS)

+3 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Active Control

Group I: Arm 2 Adjuvant Chemotherapy + Ovarian Function Suppression + Aromatase InhibitorActive Control2 Interventions

Adjuvant chemotherapy of investigator's choice followed by an aromatase inhibitor (AI) co-administered with an GnRH agonist for 5 years. The choice of AI is per investigator discretion. The choice of GnRH agonist and dosing schedule is per investigator's discretion. Options commonly include goserelin, leuprolide, or triptorelin given monthly or every-three-months. The dose and schedule of AI should be consistent with the drug package insert. Endocrine treatment beyond 5 years is at the investigator's discretion. Bilateral oophorectomy may substitute for ovarian suppression if desired.

Group II: Arm 1: Ovarian Function Suppression + Aromatase InhibitorActive Control1 Intervention

Aromatase inhibitor co-administered with a GnRH agonist (gonadotropin releasing hormone) for 5 years. The choice of AI is per investigator discretion. The choice of GnRH agonist and dosing schedule is per investigator's discretion. Options commonly include goserelin, leuprolide, or triptorelin given monthly or every-three-months. The dose and schedule of AI should be consistent with the drug package insert. Endocrine treatment beyond 5 years is at the investigator's discretion. Bilateral oophorectomy may substitute for ovarian suppression if desired.

0 / 14Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Adjuvant chemotherapy (ACT) for breast cancer typically involves cytotoxic agents that target rapidly dividing cancer cells. These agents, such as anthracyclines (e.g., doxorubicin) and taxanes (e.g., paclitaxel), work by interfering with DNA replication and cell division, leading to cancer cell death. This is crucial for breast cancer patients as it helps to reduce the risk of recurrence and improve survival rates by eliminating residual cancer cells that may remain after surgery. Understanding these mechanisms allows for better treatment planning and management of potential side effects, ultimately improving patient outcomes.

Factors influencing the interim interpretation of a breast cancer trial: danger of achieving the "expected" result.Breast Cancer Resistance to Cyclin-Dependent Kinases 4/6 Inhibitors: Intricacy of the Molecular Mechanisms.Safety profile of new anticancer drugs.