177Lu-DOTA-EB-TATE for Neuroendocrine Cancer

Overseen By Chris Pak

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Molecular Targeting Technologies, Inc.

Must not be taking: Somatostatin analogues

Disqualifiers: Pregnancy, Liver involvement, Bone marrow involvement, Infections, Diabetes, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

9 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new targeted radiation therapy for patients with advanced or hard-to-remove GEP-NETs. The therapy uses a radioactive substance that binds to cancer cells and delivers radiation directly to them.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot use somatostatin or its analogues within 4 months of the treatment, and short-acting octreotide must be stopped 24 hours before and after the treatment.

What data supports the effectiveness of the treatment 177Lu-DOTA-EB-TATE for neuroendocrine cancer?

Research shows that 177Lu-DOTA-EB-TATE is effective in treating neuroendocrine tumors, with a high rate of disease control and partial response in patients. It is well-tolerated with manageable side effects, and patients experienced significant symptom relief and improved survival outcomes. ^{1 2 3 4 5}

Is 177Lu-DOTA-EB-TATE safe for humans?

Research shows that 177Lu-DOTA-EB-TATE is generally safe for humans, with most patients tolerating the treatment well. Some patients experienced mild to moderate side effects, such as low blood cell counts and liver issues, but severe side effects were rare. ^{1 5 6 7 8}

What makes the drug 177Lu-DOTA-EB-TATE unique for treating neuroendocrine cancer?

177Lu-DOTA-EB-TATE is unique because it includes an Evans blue structure that binds to albumin, improving how the drug moves and works in the body, allowing for effective treatment with a lower dose compared to similar treatments like 177Lu-DOTA-TATE. ^{1 2 3 9 10}

Research Team

Lisa Bodei

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Adults over 18 with advanced, inoperable well-differentiated neuroendocrine tumors (GEP-NETs) that are positive for somatostatin receptors can join this trial. They must have measurable disease, agree to use contraception, and have not had certain recent treatments or other cancers. People with severe organ dysfunction, active infections like hepatitis or HIV, uncontrolled diabetes, or who are pregnant/breastfeeding cannot participate.

Inclusion Criteria

I had local therapy over 4 weeks ago.

My last surgery was more than 6 weeks ago.

Women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation, including follow-up (7 months after the last dose of study drug for women and 4 months for men)

Exclusion Criteria

I haven't used somatostatin or its analogues in the last 4 months.

I have tumors that cannot be treated with local therapies before starting the treatment.

I have no other cancers except for possibly non-melanoma skin cancer or treated cervical carcinoma in situ.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single-dose intravenous administration of 177Lu-DOTA-EB-TATE per 6-week cycle, for a total of 2 cycles, with dose escalation from 50 mCi to 150 mCi

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• 177Lu-DOTA-EB-TATE

Trial Overview The trial is testing the safety and dosage of a new treatment called 177Lu-DOTA-EB-TATE in patients with specific types of neuroendocrine tumors. It's an early-phase study focusing on how well patients tolerate the drug and how it distributes in their bodies.

Participant Groups

Group I: Peptide Receptor Radionucleotide Therapy (PRRT) Experimental Treatment 2 Interventions

The treatment regimen will consist of a single-dose intravenous administration of 177Lu-DOTA-EB-TATE per 6-week cycle, for a total of 2 cycles. The dose per cycle will be fixed for each patient and will be escalated in 3 different dose levels, from 50 mCi to 150 mCi (1.85 -5.55 GBq). Each dose of 177Lu-DOTA-EB-TATE will be administered in association with intravenous renal protective amino acid solutions.

Who Is Running the Clinical Trial?

Molecular Targeting Technologies, Inc.

Lead Sponsor

Trials

3

Recruited

80+

ClinSmart

Industry Sponsor

Trials

2

Recruited

30+

Findings from Research

In a study of 36 patients with gastroenteropancreatic neuroendocrine tumors treated with 177Lu-DOTA-TATE, 71.4% experienced symptomatic improvement, and the median overall survival was 121.7 months, indicating significant efficacy of the treatment.

The therapy was found to be safe, with only 8.9% of treatment cycles resulting in acute side effects and no significant renal or hematologic toxicity, while higher expression of somatostatin receptors correlated with better survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of Gastroenteropancreatic Neuroendocrine Tumors with 177Lu-DOTA-TATE: Experience of the Portuguese Institute of Oncology in Porto]. Sampaio, IL., Luiz, HV., Violante, LS., et al.[2019]

A ready-to-use formulation of 177Lu-DOTA-TATE was developed for treating neuroendocrine tumors, achieving over 90% radiolabeling yields and maintaining safety for human use for more than a week with high radiochemical purity.

The optimized production process allows for bulk scale preparation, ensuring consistent availability of this effective radiopharmaceutical for patient treatment across various nuclear medicine centers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bulk Scale Formulation of Therapeutic Doses of Clinical Grade Ready-to-Use 177Lu-DOTA-TATE: The Intricate Radiochemistry Aspects. Mathur, A., Prashant, V., Sakhare, N., et al.[2018]

The pilot study involving 4 patients with advanced neuroendocrine neoplasms (NEN) showed that a single low dose of 177Lu-DOTA-EB-TATE was well-tolerated without significant adverse effects, leading to symptomatic remission in all patients.

177Lu-DOTA-EB-TATE demonstrated a significant reduction in tumor uptake (SUVmax) in 72.5% of tumors, indicating its efficacy, and it achieved similar results to the higher dose of 177Lu-DOTA-TATE therapy, suggesting potential advantages for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response to Single Low-dose 177Lu-DOTA-EB-TATE Treatment in Patients with Advanced Neuroendocrine Neoplasm: A Prospective Pilot Study. Wang, H., Cheng, Y., Zhang, J., et al.[2019]

177Lu-DOTA-TATE therapy is highly effective for treating metastatic, well-differentiated, somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (NETs), with mostly tolerable side effects.

This therapy is typically used as a second-line treatment after somatostatin analogs (SSA) for gastroenteric NETs and as a second or third-line option for pancreatic NETs, potentially improving survival rates and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastro-Enteric-Pancreatic Neuroendocrine Tumor Treatment: 177Lu-DOTATATE. Sanli, Y., Denizmen, D., Subramaniam, RM.[2023]

177Lu-DOTA-EB-TATE treatment for metastatic neuroendocrine tumors (NETs) showed a good safety profile, with no grade 4 toxicities and only mild to moderate adverse effects in a study of 30 patients over a median follow-up of 46 months.

The treatment demonstrated significant efficacy, achieving a disease control rate of 85.2% and a median progression-free survival of 36 months, indicating it is an effective option for managing metastatic NETs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of peptide receptor radionuclide therapy with 177Lu-DOTA-EB-TATE in patients with metastatic neuroendocrine tumors. Jiang, Y., Liu, Q., Wang, G., et al.[2022]

The guideline for treating neuroendocrine tumors with Lu-177-DOTA-TATE emphasizes radiation safety and has been approved by the Japanese Society of Nuclear Medicine, ensuring a standardized approach in Japan.

While specific to Japan, the radiation protection issues addressed in this guideline are relevant and beneficial for international practices in the treatment of neuroendocrine tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Manual on the proper use of lutetium-177-labeled somatostatin analogue (Lu-177-DOTA-TATE) injectable in radionuclide therapy (2nd ed.). Hosono, M., Ikebuchi, H., Nakamura, Y., et al.[2018]

A study of 32 administrations of [177Lu]Lu-DOTA-TATE showed that using lead aprons significantly reduced radiation exposure for medical staff, with reductions of up to 71% for physicians and 68% for nurses.

The average radiation dose measured was consistent across different monitoring methods, indicating that with proper safety measures, administering [177Lu]Lu-DOTA-TATE can be done safely, although regular monitoring is essential to stay within annual dose limits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation exposure assessment of nuclear medicine staff administering [177Lu]Lu-DOTA-TATE with active and passive dosimetry. Riveira-Martin, M., Struelens, L., Muñoz Iglesias, J., 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]

The study demonstrated that both 68Ga-DOTA-TATE and 177Lu-DOTA-TATE effectively accumulate in neuroendocrine tumors in animal models, indicating their potential for targeted imaging and therapy.

Clinical imaging with 68Ga-DOTA-TATE in neuroendocrine tumor patients successfully identified primary and metastatic lesions, suggesting its utility in improving diagnosis and treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

68Ga/177Lu-labeled DOTA-TATE shows similar imaging and biodistribution in neuroendocrine tumor model. Liu, F., Zhu, H., Yu, J., et al.[2017]

177Lu-DOTA-EB-TATE is well tolerated in patients with progressive metastatic neuroendocrine tumors, with no severe hematotoxicity, nephrotoxicity, or hepatotoxicity observed in most treatment groups.

The treatment showed greater efficacy compared to the standard 177Lu-DOTATATE, particularly at higher doses (1.85 GBq and 3.7 GBq), leading to significant decreases in tumor uptake as measured by SUVmax.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose escalation of an Evans blue-modified radiolabeled somatostatin analog 177Lu-DOTA-EB-TATE in the treatment of metastatic neuroendocrine tumors. Liu, Q., Cheng, Y., Zang, J., et al.[2022]

References

1. Portugal pubmed.ncbi.nlm.nih.gov

[Treatment of Gastroenteropancreatic Neuroendocrine Tumors with 177Lu-DOTA-TATE: Experience of the Portuguese Institute of Oncology in Porto]. [2019]

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

Bulk Scale Formulation of Therapeutic Doses of Clinical Grade Ready-to-Use 177Lu-DOTA-TATE: The Intricate Radiochemistry Aspects. [2018]

3. Australia pubmed.ncbi.nlm.nih.gov

Response to Single Low-dose 177Lu-DOTA-EB-TATE Treatment in Patients with Advanced Neuroendocrine Neoplasm: A Prospective Pilot Study. [2019]

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

Gastro-Enteric-Pancreatic Neuroendocrine Tumor Treatment: 177Lu-DOTATATE. [2023]

5. Australia pubmed.ncbi.nlm.nih.gov

Safety and efficacy of peptide receptor radionuclide therapy with 177Lu-DOTA-EB-TATE in patients with metastatic neuroendocrine tumors. [2022]

6. Japan pubmed.ncbi.nlm.nih.gov

Manual on the proper use of lutetium-177-labeled somatostatin analogue (Lu-177-DOTA-TATE) injectable in radionuclide therapy (2nd ed.). [2018]

7. Germany pubmed.ncbi.nlm.nih.gov

Radiation exposure assessment of nuclear medicine staff administering [177Lu]Lu-DOTA-TATE with active and passive dosimetry. [2023]

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

Lutetium Lu-177 Dotatate Flare Reaction. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

68Ga/177Lu-labeled DOTA-TATE shows similar imaging and biodistribution in neuroendocrine tumor model. [2017]

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

Dose escalation of an Evans blue-modified radiolabeled somatostatin analog 177Lu-DOTA-EB-TATE in the treatment of metastatic neuroendocrine tumors. [2022]