Sacituzumab Govitecan for Brain Metastases from Breast Cancer

Not currently recruiting at 301 trial locations

Overseen By Dana Sparks

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: SWOG Cancer Research Network

Must not be taking: Antiretrovirals, Antiepileptics, Warfarin, others

Disqualifiers: Seizures, HIV, Hepatitis, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 24

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called sacituzumab govitecan for individuals with HER2-negative breast cancer that has spread to the brain. Sacituzumab govitecan combines a targeted therapy, which attaches to specific cancer cells, with a chemotherapy drug to potentially shrink brain tumors and slow their growth. The trial seeks participants whose breast cancer has progressed to the brain after previous treatments, such as radiation. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before joining. You must not have taken specific cancer treatments, enzyme-inducing anti-epileptic drugs, or warfarin shortly before starting the trial. If you're on HIV medications that interact with the trial drug, you may need to switch to different ones.

Is there any evidence suggesting that sacituzumab govitecan is likely to be safe for humans?

Research has shown that sacituzumab govitecan is generally well-tolerated by patients. This treatment combines a specific antibody with a chemotherapy drug and has proven effective for certain types of breast cancer. In past studies, patients with advanced breast cancer lived longer without disease progression when using sacituzumab govitecan compared to standard chemotherapy.

Earlier studies have examined the side effects of sacituzumab govitecan. While some patients experienced side effects, they were often manageable. Common side effects included nausea, diarrhea, and low blood cell counts, which are typical for many cancer treatments.

The FDA has already approved sacituzumab govitecan for other types of cancer, indicating that its safety is well-understood. Doctors know how to manage its side effects. Overall, while all medications can have risks, sacituzumab govitecan is considered to have a well-studied safety profile. ^{1 2 3 4 5}

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

Sacituzumab govitecan is unique because it combines an antibody with a chemotherapy drug, directly targeting cancer cells. This approach, known as an antibody-drug conjugate, allows for more precise delivery of treatment, potentially reducing the impact on healthy cells compared to traditional chemotherapies. Researchers are excited because it targets Trop-2, a protein often overexpressed in breast cancer, which may offer a new way to combat brain metastases from breast cancer. Unlike standard treatments such as surgery, radiation, or other chemotherapies, sacituzumab govitecan offers a targeted mechanism that could improve outcomes and reduce side effects.

What evidence suggests that sacituzumab govitecan might be an effective treatment for brain metastases from breast cancer?

Research has shown that sacituzumab govitecan can help treat certain types of advanced breast cancer. In studies, patients with metastatic breast cancer, where the cancer has spread, lived longer without their cancer worsening when taking this drug compared to traditional chemotherapy. Sacituzumab govitecan targets specific proteins on cancer cells, delivering chemotherapy directly to them. This targeted approach helps kill cancer cells more effectively. While research continues on its effects on breast cancer that has spread to the brain, the drug shows promise due to its success in treating other types of metastatic breast cancer. Participants in this trial will receive sacituzumab govitecan to evaluate its effectiveness specifically for brain metastases from breast cancer. ^{1 2 3 6 7}

Who Is on the Research Team?

Andrew J Brenner

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

This trial is for adults with HER2-negative breast cancer that has spread to the brain. They must have measurable brain metastasis, experienced CNS progression after treatment, and be in good physical condition (Zubrod status 0 or 1). Patients should not have had more than two seizures recently, no recent certain treatments or infections like HIV/hepatitis, and cannot be pregnant.

Inclusion Criteria

I have another cancer, but it won't affect this trial's treatment.

I am fully active or restricted in physically strenuous activity but can do light work.

My heart is functioning well.

Exclusion Criteria

I have had 2 or fewer seizures in the last 28 days.

Participants must not be pregnant or nursing

I haven't taken any cancer-targeting drugs in the last 21 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sacituzumab govitecan intravenously over 1-3 hours on days 1 and 8. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Up to 2 years

Visits every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-ups every 3 months for 1 year and then every 6 months for another year.

2 years

Every 3 months for 1 year, then every 6 months for 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Sacituzumab Govitecan

Trial Overview

The trial tests Sacituzumab Govitecan's effectiveness on patients with brain metastases from breast cancer. It's a targeted therapy combining an antibody with chemotherapy to attack cancer cells directly without harming normal cells.

How Is the Trial Designed?

Group I: Treatment (sacituzumab govitecan) Experimental Treatment 1 Intervention

Patients receive sacituzumab govitecan IV over 1-3 hours on days 1 and 8. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Sacituzumab Govitecan is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Trodelvy for:

• Metastatic triple-negative breast cancer
• Locally advanced or metastatic urothelial cancer (withdrawn)
• Metastatic HR+/HER2- breast cancer

Approved in European Union as Trodelvy for:

• Metastatic triple-negative breast cancer

Approved in Canada as Trodelvy for:

• Metastatic triple-negative breast cancer

Who Is Running the Clinical Trial?

SWOG Cancer Research Network

Lead Sponsor

Trials

403

Recruited

267,000+

Southwest Oncology Group

Lead Sponsor

Trials

389

Recruited

260,000+

Gilead Sciences

Industry Sponsor

Trials

1,150

Recruited

878,000+

Daniel O'Day

Gilead Sciences

Chief Executive Officer since 2019

MBA from Columbia University

Dietmar Berger

Gilead Sciences

Chief Medical Officer

MD and PhD from Albert-Ludwigs University School of Medicine

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

The combination of lapatinib and capecitabine (LC) showed an overall response rate of 33.3% in 21 patients with HER2-positive breast cancer brain metastases, indicating it is an effective treatment option.

The treatment was well-tolerated, with manageable side effects, and resulted in a median progression-free survival of 5.5 months and overall survival of 11 months, suggesting it is a viable option for patients who have progressed after other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

All-oral combination of lapatinib and capecitabine in patients with brain metastases from HER2-positive breast cancer--a phase II study. Shawky, H., Tawfik, H.[2022]

Younger age, negative hormone receptor status, and specific genetic mutations (like BRCA1) are linked to a higher risk of developing CNS metastases in breast cancer patients, influencing treatment decisions.

Surgery combined with whole brain radiation therapy (WBRT) is effective for patients with a single brain metastasis, while those with multiple metastases may benefit from stereotactic radiosurgery, highlighting the importance of individual prognostic factors in treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CNS complications of breast cancer: current and emerging treatment options. Kaal, EC., Vecht, CJ.[2021]

Trastuzumab deruxtecan (T-DXd) effectively inhibited tumor growth and improved survival in patient-derived xenograft models of HER2-positive and HER2-low breast cancer brain metastases, indicating its potential as a treatment option for these patients.

In a retrospective study of 17 patients with brain metastases, T-DXd showed a CNS objective response rate of 73%, suggesting significant clinical efficacy, especially in those with untreated or progressive brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical and Clinical Efficacy of Trastuzumab Deruxtecan in Breast Cancer Brain Metastases. Kabraji, S., Ni, J., Sammons, S., et al.[2023]

In the LANDSCAPE study, a combination of capecitabine and lapatinib showed a significant volumetric response in about two-thirds of HER2-positive breast cancer patients with untreated brain metastases, indicating promising efficacy despite the challenges posed by the blood-brain barrier.

These findings suggest that targeted therapies like capecitabine and lapatinib could change treatment strategies for selected patients with brain metastases, highlighting the need for innovative approaches to improve survival rates in this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Systemic treatment of brain metastases from breast cancer: cytotoxic chemotherapy and targeted therapies]. Bachelot, T., Le Rhun, E., Labidi-Gally, I., et al.[2018]

In a study of 80 patients with brain metastases from HER2-positive breast cancer, the addition of lapatinib to trastuzumab significantly improved overall survival, with a median survival not reached in the lapatinib group compared to 13 months for trastuzumab alone.

Lapatinib was identified as an independent positive predictor for survival, suggesting that patients with a Karnofsky Performance Score of 70 or higher may benefit from this combination therapy after local treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of anti-HER2 therapy on overall survival in HER2-overexpressing breast cancer patients with brain metastases. Bartsch, R., Berghoff, A., Pluschnig, U., et al.[2021]

In a study of breast cancer patients with HER-2/neu overexpression, targeted therapy using lapatinib and/or trastuzumab combined with chemotherapy (capecitabine) resulted in a 55.9% objective response rate in brain metastases.

The treatment led to complete regression in 14.7% of cases and partial regression in 41.2%, along with significant improvements in patients' quality of life due to symptom relief and good tolerability of the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Current possibilities of targeted therapy in the treatment of breast cancer with overexpression of HER-2/neu and metastatic lesions in the brain]. Naskhletashvili, DR., Gorbunova, VA., Moskvina, EA.[2018]

Lapatinib, a drug that can cross the blood-brain barrier, showed effectiveness in shrinking brain metastases in a patient with HER2-positive breast cancer after other treatments failed.

This case suggests that while trastuzumab may help control breast cancer micro-metastases, it may not prevent their progression to the brain, highlighting lapatinib as a potential treatment option for patients with brain metastasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effective Treatment of Solitary Pituitary Metastasis with Panhypopituitarism in HER2-Positive Breast Cancer by Lapatinib. Park, Y., Kim, H., Kim, EH., et al.[2018]

In a study of 87 advanced breast cancer patients treated with trastuzumab, 30% developed brain metastases within one year, highlighting the high incidence of this complication in HER2 positive cases.

Among patients who benefited from trastuzumab, 21% experienced disease progression first in the brain, suggesting that the brain may act as a 'sanctuary site' for cancer relapse despite treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence, pattern and timing of brain metastases among patients with advanced breast cancer treated with trastuzumab. Yau, T., Swanton, C., Chua, S., et al.[2015]

In a case study of a woman with HER2-positive metastatic breast cancer, the continuation of trastuzumab alongside systemic chemotherapy led to multiple treatment responses and prolonged survival despite the presence of brain metastases.

This suggests that trastuzumab may not only help control systemic disease but could also have a direct beneficial effect on brain metastases, which is a novel finding in the treatment of this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HER2-positive breast cancer brain metastases: multiple responses to systemic chemotherapy and trastuzumab--a case report. Church, DN., Bahl, A., Jones, A., et al.[2018]

Citations

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clinicaltrials.gov

clinicaltrials.gov/study/NCT06462079?term=AREA%5BConditionSearch%5D(Brain%20Metastases)%20AND%20AREA%5BOverallStatus%5D(NOT_YET_RECRUITING%20OR%20RECRUITING)&rank=2

Study Details | NCT06462079 | Sacituzumab Govitecan ...

This study is an open, uncontrolled phase II clinical study to observe the efficacy and safety of Sacituzumab Govitecan combined with intracranial radiotherapy ...

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askgileadmedical.com

askgileadmedical.com/docs/trodelvy/trodelvy-use-in-patients-with-brain-metastases-in-metastatic-breast-cancer-studies

Trodelvy® (sacituzumab govitecan-hziy) Use in Patients ...

An open-label, phase 2 study (NCT04647916) is evaluating the efficacy and safety of SG in HER2- breast cancer that has metastasized to the brain. Clinical Data ...

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nature.com

nature.com/articles/s41467-024-50558-9

Sacituzumab Govitecan in patients with breast cancer brain ...

Sacituzumab Govitecan (SG) is an antibody-drug conjugate that has demonstrated efficacy in patients with TROP-2 expressing epithelial cancers.

4.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa2028485

Sacituzumab Govitecan in Metastatic Triple-Negative ...

Progression-free and overall survival were significantly longer with sacituzumab govitecan than with single-agent chemotherapy among patients with metastatic ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12173046/

Effectiveness of sacituzumab govitecan and management ...

We describe the real-world effectiveness of SG as 2L+ mTNBC treatment and the proportion of patients with neutropenia and its management.

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clinicaltrials.gov

clinicaltrials.gov/study/NCT01631552

Study of Sacituzumab Govitecan-hziy (IMMU-132) in Adults ...

The primary objective in Phase I is to evaluate the safety and tolerability of sacituzumab govitecan-hziy (SG) as a single agent administered in 21-day ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11083716/

The Safety and Efficacy of the Combination of Sacituzumab ...

We conducted a multi-center retrospective cohort study to assess the efficacy and safety of Sacituzumab govitecan and palliative radiotherapy.