177Lu-DOTATATE for Advanced Breast Cancer

Overseen By Rodney F Pommier

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: OHSU Knight Cancer Institute

Must not be taking: Somatostatin analogs

Disqualifiers: Brain metastases, Uncontrolled diabetes, 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 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a new treatment called 177Lu-DOTATATE (Lutathera) for patients with advanced breast cancer that has either spread to other parts of the body (stage IV) or recurred after treatment. The treatment uses a radioactive agent to specifically target and kill cancer cells with a certain marker (SSTR2). This approach could help reduce tumor size and the number of cancer cells in the blood. Suitable candidates for this trial have experienced breast cancer spread or recurrence and have already tried at least two other treatments without success. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop taking short-acting somatostatin analogs 24 hours before and after the treatment, and long-acting somatostatin analogs at least 4 weeks before the treatment. Other chemotherapy or targeted therapy must be stopped 4 weeks prior to enrollment.

Is there any evidence suggesting that 177Lu-DOTATATE is likely to be safe for humans?

Research has shown that Lutetium Lu 177 Dotatate is generally safe for people. One study found that most patients tolerated the treatment well, and it worked as expected without causing serious problems. Another study found that 17% of patients with certain tumors showed improvement, indicating its effectiveness and safety.

Lutetium Lu 177 Dotatate is a targeted therapy, focusing directly on cancer cells, which may help protect healthy cells. This treatment has been used safely in other conditions, providing some confidence about its use in advanced breast cancer as well. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for advanced breast cancer, which typically include chemotherapy, hormone therapy, and targeted therapies, Lutetium Lu 177 Dotatate offers a novel approach by utilizing targeted radiotherapy. This treatment is unique because it delivers radiation directly to cancer cells through a process called peptide receptor radionuclide therapy (PRRT), which binds to specific receptors on the tumor. Researchers are excited about this treatment because it has the potential to minimize damage to healthy cells while effectively targeting and destroying cancerous ones, offering a promising alternative for patients with advanced stages of the disease.

What evidence suggests that 177Lu-DOTATATE might be an effective treatment for advanced breast cancer?

Research has shown that 177Lu-DOTATATE, which participants in this trial will receive, may help treat advanced cancers. In one study, patients who received this treatment had their cancer remain stable for an average of 17.43 months. This treatment targets cancer cells with a specific marker, SSTR2, and delivers radiation to destroy them. Another study found that 17% of patients experienced some tumor shrinkage. Overall, these findings suggest that 177Lu-DOTATATE could help reduce tumor size and slow the progression of advanced breast cancer. ^{3 4 6 7 8}

Who Is on the Research Team?

Rodney F Pommier

Principal Investigator

OHSU Knight Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults with stage IV or recurrent breast cancer that has progressed after at least two standard treatments. Participants must have tumors positive for SSTR2, adequate organ function, and agree to use effective contraception. Exclusions include other cancers within 5 years (except certain skin/cervical cancers), brain metastases, uncontrolled conditions like diabetes or heart failure, recent surgeries or therapies, and pregnancy.

Inclusion Criteria

Your kidney function needs to be good, which means the level of creatinine in your blood or the amount of creatinine cleared by your kidneys needs to be within a certain range.

Your platelet count is 75,000 or higher per microliter of blood.

Participant must consent to undergo a pre-treatment screening biopsy for enrollment

Exclusion Criteria

You have had cancer, but it has been completely treated and there has been no sign of it for at least 5 years, except for non-melanoma skin cancer or early stage cervical cancer that has been treated.

You have received radiation treatment to a large portion of your bone marrow in the past.

You have brain metastases that have not been treated and stabilized.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive 177Lu-DOTATATE IV over 30-40 minutes during weeks 1, 8, 16, and 24

24 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Lutetium Lu 177 Dotatate

Trial Overview

The trial tests the effectiveness of a targeted therapy called 177Lu-DOTATATE in patients with advanced breast cancer. This drug attaches to tumor cells expressing SSTR2 and delivers radiation directly to destroy them. The goal is to reduce tumor size and circulating cancer stem cells.

How Is the Trial Designed?

Group I: Treatment (177Lu-DOTATATE) Experimental Treatment 6 Interventions

Patients receive 177Lu-DOTATATE IV over 30-40 minutes during weeks 1, 8, 16, and 24 in the absence of disease progression or unacceptable toxicity. Patients also receive Ga 68-DOTATATE and undergo PET/CT during screening, biopsy as clinically-indicated as well as CT and/or MRI and collection of blood samples throughout the study.

Lutetium Lu 177 Dotatate is already approved in European Union, United States for the following indications:

Approved in European Union as Lutathera for:

• Gastroenteropancreatic neuroendocrine tumors

Approved in United States as Lutathera for:

• Gastroenteropancreatic neuroendocrine tumors

Who Is Running the Clinical Trial?

OHSU Knight Cancer Institute

Lead Sponsor

Trials

239

Recruited

2,089,000+

Advanced Accelerator Applications USA Inc

Collaborator

Trials

1

Recruited

10+

Novartis Pharmaceuticals

Industry Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Advanced Accelerator Applications

Industry Sponsor

Trials

37

Recruited

3,000+

Novartis

Industry Sponsor

Trials

1,646

Recruited

2,778,000+

Vasant Narasimhan

Novartis

Chief Executive Officer since 2018

MD from Harvard Medical School, Bachelor's in Biological Sciences from University of Chicago, Master's in Public Policy from John F. Kennedy School of Government

Shreeram Aradhye

Novartis

Chief Medical Officer since 2022

MD from Yale University, MSc in Clinical Epidemiology from University of Pennsylvania

Oregon Health and Science University

Collaborator

Trials

1,024

Recruited

7,420,000+

Published Research Related to This Trial

The study successfully demonstrated that pharmacokinetic parameters of Lu-177 DOTATATE can be derived from SPECT/CT imaging, allowing for non-invasive monitoring of drug distribution in patients with neuroendocrine tumors.

The findings revealed significant differences in drug clearance and distribution between blood and bone marrow, suggesting that individual patient characteristics, such as weight, can be used to optimize personalized dosing strategies for improved treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Pharmacokinetics of Radiopharmaceuticals from SPECT/CT Image Acquisition by Contouring in Patients with Gastroenteropancreatic Neuroendocrine Tumors: Lu-177 DOTATATE (Lutathera®) Case. Barakat, A., Santoro, L., Vivien, M., et al.[2023]

The LUTIA study is a multicenter randomized controlled trial involving 26 patients with unresectable grade I or II neuroendocrine tumors, aiming to compare intra-arterial (IA) administration of 177Lu-DOTATATE to conventional intravenous (IV) administration to enhance tumor-absorbed doses in liver metastases.

The primary goal is to determine if IA treatment leads to a higher tumor-to-non-tumor uptake ratio of 177Lu-DOTATATE in liver metastases, which could potentially improve treatment response and survival rates for patients with bulky liver metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intra-arterial versus standard intravenous administration of lutetium-177-DOTA-octreotate in patients with NET liver metastases: study protocol for a multicenter, randomized controlled trial (LUTIA trial). Ebbers, SC., Braat, AJAT., Moelker, A., et al.[2020]

In a study of 79 patients with progressive neuroendocrine tumors treated with Lu-DOTATATE, 13% showed a partial response and 64% had stable disease, with a median time to progression of 28 months overall.

The treatment was found to be safe, with only a few patients experiencing mild toxicity, including grade 1 haematotoxicity and nephrotoxicity, supporting its use as an effective option for managing these tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early efficacy of and toxicity from lutetium-177-DOTATATE treatment in patients with progressive metastatic NET. Pencharz, D., Walker, M., Yalchin, M., et al.[2019]

In a study of 38 patients with stage IV neuroendocrine tumors, lutetium-177 (177Lu)-DOTATATE therapy significantly improved global health-related quality of life from the start of treatment to three months after completion.

Patients reported notable reductions in nausea, vomiting, and gastrointestinal symptoms, indicating that 177Lu-DOTATATE therapy not only enhances overall well-being but also alleviates specific disease-related symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective Cohort Real-World Study on Neuroendocrine Tumor Patient's Quality of Life During Peptide Receptor Radionuclide Therapy With 177Lu-DOTATATE. Ramim, JE., Matheos de Lima, BA., Bulzico, DA., et al.[2023]

Citations

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clinicaltrials.gov

clinicaltrials.gov/study/NCT04529044

Study Details | NCT04529044 | 177Lu-DOTATATE for the ...

This phase II trial investigates how well 177Lu-DOTATATE works in treating patients with breast cancer that is stage IV or has come back (recurrent).

2.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.6108

Outcomes with 177 lutetium-dotatate (177Lu- ...

At a median follow-up of 19.8 months from starting 177Lu-dotatate, the median progression-free survival (PFS) was 17.43 mo. (95%CI 8.29-NE). For ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10142322/

Lutathera® Orphans: State of the Art and Future Application of ...

[177Lu]Lu-DOTATATE monotherapy protocol resulted in the highest 5-year OS (61.4%), despite tandem protocol ([90Y]Y-DOTATOC + [177Lu]Lu-DOTATATE) ...

4.

frontiersin.org

frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1393317/full

Long-term clinical outcomes of [ 177 Lu]Lu-DOTATATE in ...

The ORR in patients who received [177Lu]Lu-DOTATATE in the 2nd line was 37.5%, 40% in the 3rd line, and 25% in the 4th line. The most frequently ...

5.

onclive.com

onclive.com/view/lutetium-lu-177-dotatate-yields-partial-responses-in-metastatic-bronchopulmonary-neuroendocrine-tumors

Lutetium Lu 177 Dotatate Yields Partial Responses in ...

Lutetium Lu 177 dotatate demonstrated antitumor activity in metastatic BP-NETs, with partial responses in 17% of patients and stable disease in ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04529044

Study Details | NCT04529044 | 177Lu-DOTATATE for the ...

This phase II trial investigates how well 177Lu-DOTATATE works in treating patients with breast cancer that is stage IV or has come back (recurrent).

7.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.4131

Safety and time to response of [ 177 Lu]Lu-DOTATATE in ...

With a median TTR of 5.7 months, most responses to 177 Lu-DOTATATE occurred during scheduled treatment. Overall, the study confirmed the safety profile of 177 ...

8.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04665739

NCT04665739 | Testing Lutetium Lu 177 Dotatate in ...

Lutetium Lu 177-dotatate builds up in these cells and gives off radiation that may kill them. It is a type of radioconjugate and a type of somatostatin analog.