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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called 177Lu-DOTA-EB-TATE, a type of targeted radiotherapy, for individuals with advanced neuroendocrine cancer. It specifically targets tumors positive for somatostatin receptors. The main goal is to assess the treatment's safety and behavior in the body. Participants will receive the treatment through an IV in two cycles, each six weeks apart. The trial seeks individuals with inoperable or metastatic neuroendocrine tumors who haven't recently undergone certain treatments. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this new therapy.

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.

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

Research has shown that 177Lu-DOTA-EB-TATE is under investigation for its safety in treating neuroendocrine tumors. An earlier study found that this treatment remained in the tumors effectively, indicating potential effectiveness. However, it also accumulated in the kidneys and bone marrow, which could cause side effects.

Another study tested various doses of 177Lu-DOTA-EB-TATE. It found that doses of 1.89 and 3.97 GBq per cycle controlled tumors more effectively than a lower dose of 1.17 GBq per cycle. This suggests that higher doses might be more effective, but additional safety information is necessary for these doses.

Overall, early research appears promising. However, as this is a Phase 1 trial, the primary goal is to assess the treatment's safety and tolerability for patients. Ongoing testing will provide more detailed safety information. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for neuroendocrine cancer, which often include surgical removal, chemotherapy, or targeted therapies like somatostatin analogs, 177Lu-DOTA-EB-TATE offers a novel approach through Peptide Receptor Radionucleotide Therapy (PRRT). This treatment uses a radioactive compound, 177Lu, linked to a peptide that specifically targets cancer cells, delivering radiation directly to the tumor while minimizing damage to healthy tissue. Researchers are excited because this method allows for precise targeting of cancer cells, potentially leading to better outcomes and fewer side effects compared to conventional therapies. Additionally, the treatment's ability to escalate doses safely could enhance its effectiveness against tumors that are resistant to lower-dose therapies.

What evidence suggests that 177Lu-DOTA-EB-TATE might be an effective treatment for neuroendocrine cancer?

Studies have shown that 177Lu-DOTA-EB-TATE, the treatment tested in this trial, effectively controls tumors in patients with neuroendocrine tumors (NETs). Research indicates that doses between 1.89 and 3.97 GBq per cycle manage tumor growth better than lower doses. In this trial, participants will receive a single-dose intravenous administration of 177Lu-DOTA-EB-TATE per 6-week cycle, with doses escalated in three levels from 50 mCi to 150 mCi (1.85 - 5.55 GBq). Initial findings suggest that even a single low-dose treatment can positively affect advanced NETs. This treatment targets specific proteins called somatostatin receptors, often found in NETs, delivering radiation directly to the tumor cells to stop their growth. Early studies are promising, showing potential for this treatment to help those with difficult-to-treat NETs. ^{1 2 4 5 6}

Who Is on the Research Team?

Lisa Bodei

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9516233/

Safety and efficacy of peptide receptor radionuclide ... Rationale: This study aimed to assess the safety, efficacy, and survival of 177Lu-DOTA-EB-TATE in patients with metastatic neuroendocrine tumors (NETs).

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05475210

Study Details | NCT05475210 | 177Lu-DOTA-EB-TATE in ... 177Lu-DOTA-EB-TATE in Adult Patients With Advanced, Well- Differentiated Neuroendocrine Tumors. ClinicalTrials.gov ID NCT05475210. Sponsor Molecular Targeting ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6010978/

Response to Single Low-dose 177Lu-DOTA-EB-TATE ... This pilot study aims to evaluate the efficacy of a single low-dose treatment using 177Lu-DOTA-EB-TATE in patients with advanced neuroendocrine neoplasm (NEN).

4. jnm.snmjournals.org jnm.snmjournals.org/content/62/3/386

Peptide Receptor Radionuclide Therapy of Late-Stage ... 177 Lu-DOTA-EB-TATE doses of 1.89 and 3.97 GBq/cycle were effective in tumor control and more effective than 1.17 GBq/cycle.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03478358

NCT03478358 | Treatment Using 177Lu-DOTA-EB-TATE ... This study was designed to compare the efficacy of a long-lasting radiolabeled somatostatin analogue 177Lu-DOTA-EB-TATE with 177Lu-DOTA-TATE in patients with ...

6. jnm.snmjournals.org jnm.snmjournals.org/content/59/11/1699

Safety, Pharmacokinetics, and Dosimetry of a Long-Acting ... 177 Lu-DOTA-EB-TATE showed remarkably higher uptake and retention in NETs as well as significantly increased accumulation in the kidneys and red marrow.