Lu-DOTA-TATE for Neuroendocrine Cancer

Overseen By David Laidely, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Must not be taking: Cytotoxic chemotherapy, mTOR inhibitors

Disqualifiers: Uncontrolled diabetes, Brain metastases, Pregnancy, Breastfeeding, 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

Compensation: Varies

Number of Visits: Unknown

Duration: Varies per patient

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Lu-DOTA-TATE, a type of targeted radiotherapy, for individuals with neuroendocrine tumors, a cancer affecting hormone-producing cells. The trial aims to assess how well this treatment controls symptoms, prevents disease progression, and improves patients' quality of life. Ensuring the treatment's safety is also crucial. Suitable candidates for this trial include those with a somatostatin receptor-positive tumor, identifiable on a specific scan, who have been living with neuroendocrine cancer. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

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, it mentions that certain treatments like surgery, radiation, or chemotherapy should not have been changed within 12 weeks before joining the trial.

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

Research has shown that Lu-DOTA-TATE is generally safe for treating neuroendocrine tumors. Studies have found that although some kidney issues may occur related to the dose, the treatment remains safe and effective. Patients receiving Lu-DOTA-TATE have experienced longer periods without disease progression compared to those on other treatments. Reports suggest that it is well-tolerated and provides good disease control, even when used again after the initial treatment. These findings indicate that Lu-DOTA-TATE is a promising option with manageable side effects for many patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Lu-DOTA-TATE is unique because it uses Lutetium-177 Octreotate, a radiopharmaceutical that specifically targets neuroendocrine cancer cells. Unlike traditional chemotherapy, which can affect both healthy and cancerous cells, Lu-DOTA-TATE delivers targeted radiation directly to the tumor, potentially reducing side effects and improving effectiveness. Researchers are excited about this treatment because it offers a more focused approach, which could lead to better outcomes for patients with neuroendocrine cancer, especially those who have not responded well to other therapies.

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

Studies have shown that Lu-DOTA-TATE effectively treats neuroendocrine tumors. It extends the period during which the cancer does not worsen by 14 months in patients with advanced conditions. Research also indicates that it helps patients live longer. In this trial, participants will receive Lu-DOTA-TATE either as a primary therapy or as a secondary therapy if they previously received the treatment under a special access program. Patients treated with this drug report better outcomes compared to those receiving standard treatment. This suggests that Lu-DOTA-TATE helps control the disease and improve patients' quality of life. ^{2 3 4 5 6}

Who Is on the Research Team?

David Laidley, MD

Principal Investigator

London Health Sciences Centre & Lawson Health Research Institute

Are You a Good Fit for This Trial?

This trial is for individuals aged 14-90 with somatostatin receptor positive tumors, who have a life expectancy of more than 26 weeks and good organ function. They must not be pregnant or breastfeeding, have uncontrolled diabetes, brain metastases unless stable for 6+ months, or had certain treatments within the last 12 weeks.

Inclusion Criteria

Provide written informed consent prior to enrollment.

My kidney function tests are within the required range.

I meet all the required criteria for secondary therapy in the study.

Exclusion Criteria

My blood sugar levels are not under control and are much higher than normal.

I haven't had major cancer treatments or changed my Sandostatin LAR dose in the last 12 weeks.

I am not eligible for Group B if I meet certain criteria.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Lu-DOTA-TATE (Lutetium-177 Octreotate) by intravenous infusion

Varies per patient

Multiple visits for infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment

7 years

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Lu-DOTA-TATE

Trial Overview The study tests Lu-DOTA-TATE's effectiveness in patients with neuroendocrine carcinoma by observing how long they live without disease progression and overall survival. It also evaluates safety and quality of life impacts.

How Is the Trial Designed?

Group I: Secondary Therapy with Lu-DOTA-TATE Experimental Treatment 1 Intervention

Patients who have received previous treatment with Lu-DOTA-TATE (Lutetium-177 Octreotate) under the special access program are eligible to be treated in this study. Patients will receive Lu-DOTA-TATE by intravenous infusion.

Group II: Primary Therapy with Lu-DOTA-TATE Experimental Treatment 1 Intervention

Lu-DOTA-TATE (Lutetium-177 Octreotate) will be administered by intravenous infusion to participants who have not been previously treated with Lu-DOTA-TATE

Who Is Running the Clinical Trial?

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

678

Recruited

421,000+

London Health Sciences Centre OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

668

Recruited

424,000+

London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

686

Recruited

427,000+

Lawson Health Research Institute

Lead Sponsor

Trials

684

Recruited

432,000+

Published Research Related to This Trial

[177Lu]Lu-DOTA-TATE is an effective treatment for adult patients with somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (NETs) who have not responded to first-line somatostatin analogs, addressing a critical need in advanced cases.

The treatment process for PRRT is complex but manageable, with care coordinators ensuring smooth communication and scheduling between primary oncologists and specialists, which is essential for patient care continuity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Best Practices for the Coordinated Care of Patients With Neuroendocrine Tumors Undergoing Peptide Receptor Radionuclide Therapy. Hendifar, AE., Mehr, SH., McHaffie, DR.[2023]

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-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]

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]

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]

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]

The optimized protocol for preparing (177)Lu-DOTA-TATE allows for high specific activity and radiochemical purity, achieving a purity of 98.25% and specific activity ranging from 32.74 to 65.49 GBq/μmol across 100 batches prepared in India.

This method has successfully facilitated the administration of 250 patient doses to 150 individuals with inoperable neuroendocrine tumors, highlighting its potential efficacy as a treatment option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preparation of patient doses of (177)Lu-DOTA-TATE using indigenously produced (177)Lu: the Indian experience. Das, T., Chakraborty, S., Kallur, KG., et al.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38851203/

[ 177 Lu]Lu-DOTA-TATE plus long-acting octreotide versus ... First-line 177 Lu-Dotatate plus octreotide LAR significantly extended median progression-free survival (by 14 months) in patients with grade 2 or 3 advanced ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1607427

Phase 3 Trial of 177 Lu-Dotatate for Midgut ... Treatment with 177 Lu-Dotatate resulted in markedly longer progression-free survival and a significantly higher response rate than high-dose octreotide LAR.

3. jnm.snmjournals.org jnm.snmjournals.org/content/65/5/746

Effectiveness and Safety of Retreatment with 177Lu ... A regimen of 4 cycles of 177Lu-DOTATATE has been shown to improve both progression-free survival (PFS) and overall survival (OS) in patients ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.LBA588

[177Lu]Lu-DOTA-TATE in newly diagnosed patients with ... Conclusion: 177Lu-DOTATATE significantly prolonged PFS and demonstrated a clinically meaningful ORR, compared with high-dose octreotide LAR, in ...

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

Long-term clinical outcomes of [ 177 Lu]Lu-DOTATATE in ... The most frequently reported (>15%) nonhematologic treatment-related adverse events were fatigue, nausea, vomiting, and diarrhea. Clinically ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK587368/

Neuroendocrine Tumor 177Lutetium-Dotatate Therapy - NCBI [12][13][14] Despite dose-related renal toxicity, 177Lu-dotatate is deemed safe and effective in NEPC. Go to: Mechanism of Action. 177Lu- ...