Sacituzumab Govitecan for Brain Metastases from Breast Cancer

Recruiting at 296 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

44 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies the effect of sacituzumab govitecan in treating patients with HER2-negative breast cancer that has spread to the brain (brain metastases). Sacituzumab govitecan is a monoclonal antibody, called sacituzumab, linked to a chemotherapy drug, called govitecan. Sacituzumab is a form of targeted therapy because it attaches to specific molecules on the surface of cancer cells, known as Trop-2 receptors, and delivers govitecan to kill them. Giving sacituzumab govitecan may shrink the cancer in the brain and/or extend the time until the cancer gets worse.

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.

What data supports the effectiveness of the drug Sacituzumab Govitecan for brain metastases from breast cancer?

While there is no direct data on Sacituzumab Govitecan for brain metastases from breast cancer, other treatments like lapatinib and capecitabine have shown effectiveness in similar cases, suggesting that targeted therapies can be beneficial. Additionally, systemic treatments have shown significant antitumor activity in the central nervous system, indicating potential for drugs like Sacituzumab Govitecan. ^{1 2 3 4 5}

What makes the drug Sacituzumab Govitecan unique for treating brain metastases from breast cancer?

Sacituzumab Govitecan is unique because it is an antibody-drug conjugate, which means it combines an antibody that targets cancer cells with a chemotherapy drug, potentially allowing for more direct delivery of the treatment to cancer cells. This approach may offer a novel way to treat brain metastases from breast cancer, where traditional treatments often struggle to penetrate the blood-brain barrier effectively. ^{3 6 7 8 9}

Research Team

Andrew J Brenner

Principal Investigator

SWOG Cancer Research Network

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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 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 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]

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]

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]

References

1. England 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. [2022]

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

CNS complications of breast cancer: current and emerging treatment options. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Incidence, pattern and timing of brain metastases among patients with advanced breast cancer treated with trastuzumab. [2015]

4. England pubmed.ncbi.nlm.nih.gov

Impact of anti-HER2 therapy on overall survival in HER2-overexpressing breast cancer patients with brain metastases. [2021]

5. France pubmed.ncbi.nlm.nih.gov

[Systemic treatment of brain metastases from breast cancer: cytotoxic chemotherapy and targeted therapies]. [2018]

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

HER2-positive breast cancer brain metastases: multiple responses to systemic chemotherapy and trastuzumab--a case report. [2018]

7. Russia (Federation) 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]. [2018]

8. Korea (South) pubmed.ncbi.nlm.nih.gov

Effective Treatment of Solitary Pituitary Metastasis with Panhypopituitarism in HER2-Positive Breast Cancer by Lapatinib. [2018]

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

Preclinical and Clinical Efficacy of Trastuzumab Deruxtecan in Breast Cancer Brain Metastases. [2023]