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

10 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Lutetium Lu 177 Dotatate (Lutathera) for treating advanced breast cancer?

Lutetium Lu 177 Dotatate (Lutathera) has been shown to significantly increase survival and response rates in patients with certain types of neuroendocrine tumors, suggesting its potential effectiveness in other cancers like advanced breast cancer. ^{1 2 3 4 5}

How is the drug 177Lu-DOTATATE unique for treating advanced breast cancer?

177Lu-DOTATATE is unique because it is a targeted radionuclide therapy that uses a radioactive substance to specifically target and bind to somatostatin receptors, which are often present in certain tumors. This approach is different from traditional chemotherapy as it delivers radiation directly to the cancer cells, potentially reducing damage to healthy tissues. ^{1 4 6 7 8}

What is the purpose of this trial?

This trial is testing a treatment called 177Lu-DOTATATE for patients with advanced or recurrent breast cancer that has a specific marker (SSTR2). The treatment works by using a molecule to find cancer cells and then delivering radiation to kill them. The goal is to see if this treatment can reduce the size and number of tumors and cancer stem cells in these patients. Lutetium Lu-177 dotatate (177Lu-DOTATATE) has shown significant benefits in treating somatostatin-receptor-positive neuroendocrine tumors.

Research Team

Rodney F Pommier

Principal Investigator

OHSU Knight Cancer Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

References

1. France 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. [2023]

2. India pubmed.ncbi.nlm.nih.gov

Lutetium DOTATATE whole body scans: A novel approach for evaluation of neuroendocrine tumors. [2021]

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

Effects of treatment with (177)Lu-DOTA-Tyr(3)-octreotate on uptake of subsequent injection in carcinoid-bearing nude mice. [2019]

4. England 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). [2020]

5. United States 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. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Case Report: Primary Hypothyroidism Associated With Lutetium 177-DOTATATE Therapy for Metastatic Paraganglioma. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Personalized dosimetry of177Lu-DOTATATE: a comparison of organ- and voxel-level approaches using open-access images. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Early efficacy of and toxicity from lutetium-177-DOTATATE treatment in patients with progressive metastatic NET. [2019]