Lu-177 for Advanced Breast Cancer

(Heroine01 Trial)

Recruiting at 7 trial locations

Overseen By Rose Satz

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Advanced Imaging Projects, LLC

Must not be taking: Corticosteroids, Investigational agents

Disqualifiers: Renal issues, Bone metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

100 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you have used any other investigational therapeutic product within 30 days prior to dosing or if you require any other investigational agent before completing all scheduled study assessments.

What data supports the effectiveness of the drug Lutetium-177-DOTAGA-PEG-IAC for advanced breast cancer?

Research shows that similar treatments using Lutetium-177, like 177Lu-DOTAGA-PEG2-RM26, have effectively inhibited tumor growth in prostate cancer models and improved survival when combined with other therapies. Additionally, Lutetium-177-labeled compounds have shown promise in targeting specific cancer markers, suggesting potential effectiveness in treating advanced breast cancer. ^{1 2 3 4 5}

Is Lu-177 generally safe for use in humans?

Lu-177 therapies, like Lu-177-DOTATATE, have been used in treating certain cancers and are generally considered safe, but they can have side effects. Some reported side effects include potential toxicity to the kidneys, liver, and blood, as well as a risk of developing another cancer. However, no treatment-related toxicity was observed in a study involving Lu-177-DOTAGA-PEG2-RM26 in mice. ^{1 2 6 7 8}

What makes the drug Lu-177-DOTAGA-PEG-IAC unique for advanced breast cancer?

Lu-177-DOTAGA-PEG-IAC is unique because it uses a radioactive substance, Lutetium-177, to target and destroy cancer cells, which is different from traditional chemotherapy that uses chemicals to kill cancer cells. This approach is similar to treatments used for neuroendocrine tumors, where the radioactive component specifically targets tumor cells, potentially offering a new option for patients with advanced breast cancer. ^{5 9 10 11 12}

What is the purpose of this trial?

This trial is testing a new drug that uses radiation to target and kill cancer cells in patients with advanced breast cancer who have not responded to other treatments. The goal is to see if this drug can help shrink tumors and improve patients' quality of life.

Research Team

Stanley Satz, Ph.D.

Principal Investigator

Advanced Imaging Projects

Eligibility Criteria

This trial is for women with angiogenic breast cancer that's spread and hasn't been removed by surgery. They must have tried at least one treatment before, be over 18, not pregnant, able to follow the study plan, and have a certain level of physical fitness (ECOG score ≤3). Their organs need to function well enough to handle the trial.

Inclusion Criteria

I am capable of limited self-care.

My PET/CT scan showed positive results for a specific test.

The patient is able and willing to provide informed consent and to comply with the requirements of this trial protocol

Exclusion Criteria

Additional inclusion criterion for measure human dosimetry: Unable to comply with the requirements of the dosimetry imaging protocol

I cannot stay still for long periods due to a condition like severe arthritis.

I have had radiation therapy targeting one of my kidneys.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Assessment of safety and adequacy of a dose of HurlutinTM Lu-177 for up to three cycles, at 4-week intervals

12 weeks

3 visits (in-person)

Phase II Treatment

Demonstration of safety, dose adequacy, anti-tumor activity, and efficacy of tumor-targeted therapy using Lutetium-177-DOTAGA-IAC

6-12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Lutetium-177-DOTAGA-PEG-IAC

Trial Overview The trial tests a new drug called Lutetium-177-DOTAGA-PEG-IAC on patients with advanced breast cancer who've had previous treatments. It's an early-phase study looking at safety and effectiveness. Patients will get this drug and then be monitored using PET/CT scans.

Participant Groups

Group I: Arm 1 Experimental Treatment 1 Intervention

Single Arm study Lu-177-DOTAGA-IAC (intracutaneous) Dosage and Dose Escalation Frequency: Cohort 1: 75 mCi x 3 (maximum cumulative administered activity, 225mCi) + 100 μgr IAC Cohort 2: 150 mCi x 3 (maximum cumulative administered activity, 450mCi) + 100 μgr IAC Cohort 3: 200 mCi x 3 (maximum cumulative administered activity, 600mCi) + 100 μgr IAC Three cycles each 4 weeks apart.

Who Is Running the Clinical Trial?

Advanced Imaging Projects, LLC

Lead Sponsor

Trials

2

Recruited

130+

University of Witwatersrand, South Africa

Collaborator

Trials

107

Recruited

10,090,000+

US Department of Veterans Affairs

Collaborator

Trials

881

Recruited

502,000+

Postgraduate Institute of Medical and Research

Collaborator

Trials

1

Recruited

100+

All India Institute of Medical Sciences, New Delhi

Collaborator

Trials

196

Recruited

200,000+

Findings from Research

177Lu-DOTA-Peptide 2, a new radioantagonist, showed high stability and selective binding to somatostatin receptors in HT-29 colorectal cancer cells, indicating its potential for targeted therapy.

The study demonstrated that 177Lu-DOTA-Peptide 2 has a low internalization rate and a high tumor uptake, making it a promising candidate for radionuclide therapy in treating somatostatin receptor-positive tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical study of a new 177Lu-labeled somatostatin receptor antagonist in HT-29 human colorectal cancer cells. Behnammanesh, H., Erfani, M., Hajiramezanali, 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]

Lutetium Lu-177 dotatate is an effective treatment for gastroenteropancreatic neuroendocrine tumors, significantly improving progression-free survival, as shown in European studies.

In a study of 12 patients, tumor flare reactions were observed in 5 patients, but these reactions can be effectively managed with corticosteroids or other strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lutetium Lu-177 Dotatate Flare Reaction. Salner, AL., Blankenship, B., Dunnack, H., et al.[2022]

In a study of 47 patients with progressive well-differentiated neuroendocrine tumors (NETs) treated with 177Lu-Dotatate, the median progression-free survival was 34.1 months, indicating the treatment's efficacy in managing these tumors over time.

Factors such as having 5 or more bone metastases, non-gastroenteropancreatic NETs, high levels of chromogranin A, and pre-existing ascites were identified as significant predictors of poorer overall survival, helping to identify patients who may benefit less from this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival predictors of 177Lu-Dotatate peptide receptor radionuclide therapy (PRRT) in patients with progressive well-differentiated neuroendocrine tumors (NETS). Swiha, MM., Sutherland, DEK., Sistani, G., et al.[2022]

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]

Lutetium-177 (Lu-177) DOTATATE is an effective treatment for inoperable gastroenteropancreatic neuroendocrine tumors (GEP-NETs) that have not responded to standard therapies, as it can reduce tumor size, improve symptoms, and increase progression-free survival.

The practice parameter document ensures safe handling and administration of Lu-177 DOTATATE, providing essential guidelines for authorized users to maintain consistent and safe treatment practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ACR-ACNM-ASTRO-SNMMI Practice Parameter for Lutetium-177 (Lu-177) DOTATATE Therapy. Love, C., Desai, NB., Abraham, T., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Synthesis and comparative evaluation of 177Lu-labeled PEG and non-PEG variant peptides as HER2-targeting probes. [2022]

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

Trastuzumab cotreatment improves survival of mice with PC-3 prostate cancer xenografts treated with the GRPR antagonist 177 Lu-DOTAGA-PEG2 -RM26. [2021]

3. Iran pubmed.ncbi.nlm.nih.gov

Preclinical study of a new 177Lu-labeled somatostatin receptor antagonist in HT-29 human colorectal cancer cells. [2023]

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

A clinical score for neuroendocrine tumor patients under consideration for Lu-177-DOTATATE therapy. [2022]

5. 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]

6. 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]

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

Lutetium-177 Radiopharmeceutical Therapy Extravasation Lessons Learned. [2022]

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

Lutetium Lu-177 Dotatate Flare Reaction. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

Survival predictors of 177Lu-Dotatate peptide receptor radionuclide therapy (PRRT) in patients with progressive well-differentiated neuroendocrine tumors (NETS). [2022]

10. Germany pubmed.ncbi.nlm.nih.gov

(177)Lu-DOTATATE therapy in patients with neuroendocrine tumours: 5 years' experience from a tertiary cancer care centre in India. [2021]

11. England pubmed.ncbi.nlm.nih.gov

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

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

ACR-ACNM-ASTRO-SNMMI Practice Parameter for Lutetium-177 (Lu-177) DOTATATE Therapy. [2023]