Lu-DOTATATE for Neuroendocrine Cancer

Not currently recruiting at 3 trial locations

Overseen By Rebecca Wong, M.D.

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Must not be taking: Systemic radionuclide therapy

Disqualifiers: Curative therapy, Brain metastases, Diabetes, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 18-30 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called Lutetium-177 Octreotate (Lu-DOTATATE) to evaluate its effectiveness and safety for people with neuroendocrine tumors. These tumors must display a specific marker, the Somatostatin receptor, on a special scan to qualify for the treatment. Participants should have neuroendocrine cancer that has recently worsened and reside in Ontario. The trial aims to determine if this treatment can halt cancer progression for at least a year. As an unphased trial, it provides a unique opportunity to contribute to groundbreaking research that could benefit future patients.

Do I need to stop taking my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you have had systemic, biologic, or other radioisotope therapies within 4 weeks prior to the first dose, you may not be eligible. It's best to discuss your current medications with the trial team.

What prior data suggests that Lutetium-177 Octreotate is safe for treating neuroendocrine tumors?

Research has shown that Lutetium-177 Octreotate is generally well-tolerated by patients. In past studies, it treated neuroendocrine tumors with some success. Specifically, real-world data indicated that patients with certain neuroendocrine tumors experienced tumor shrinkage or halted growth.

Regarding safety, a review of FDA data found that while some side effects occurred, they were usually manageable. Common side effects included mild nausea, tiredness, and low blood cell counts, similar to those seen with other cancer treatments.

The FDA has already approved Lutetium-177 Octreotate for treating other types of neuroendocrine tumors, which adds confidence to its safety. This suggests that while side effects exist, they are typically not severe for most patients. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for neuroendocrine cancer, which often include surgery, chemotherapy, or somatostatin analogs, Lutetium-177 Octreotate offers a targeted approach. This treatment uses a radioactive particle, Lutetium-177, attached to a molecule that specifically seeks out and binds to cancer cells. This allows it to deliver radiation directly to the tumor, potentially reducing damage to surrounding healthy tissue. Researchers are excited because this precision could improve effectiveness while minimizing side effects compared to more traditional therapies.

What evidence suggests that Lutetium-177 Octreotate might be an effective treatment for neuroendocrine cancer?

Research shows that Lutetium-177 Octreotate, or Lu-DOTATATE, effectively treats neuroendocrine tumors. The NETTER-1 trial demonstrated that it significantly extends the time patients live without disease progression. Specifically, one study found that Lu-DOTATATE extended this period by 14 months compared to other treatments. The treatment also achieved a higher overall response rate, with more patients experiencing tumor shrinkage or halted growth. These findings suggest that Lu-DOTATATE is a promising option for individuals with advanced neuroendocrine tumors. Participants in this trial will receive Lutetium-177 Octreotate as the investigational treatment. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with biopsy-proven neuroendocrine tumors, showing progression and positive for Somatostatin receptors. They should have an ECOG performance status ≤ 2, adequate organ function, no prior radionuclide therapy or certain other treatments within the last few weeks, and not be pregnant or breastfeeding.

Inclusion Criteria

Signed informed consent

Ki-67 index ≤ 30%

My case has been reviewed by a tumor board for clinical trial suitability.

Exclusion Criteria

I am eligible for a potentially curative surgery or targeted liver therapy.

I am eligible for surgery to remove or reduce my cancer.

I haven't had radiation on the cancer we're targeting in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants undergo 4 cycles of Lu-DOTATATE treatment with dose adjustments based on individualized dosimetry

18-30 weeks

4 visits (in-person)

Follow-up

Participants are monitored for progression-free survival at 12 months from the last dose

12 months

Periodic visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Lutetium-177 Octreotate

Trial Overview The study tests Lutetium-177 Octreotate's effectiveness in patients with neuroendocrine tumors who are Somatostatin receptor-positive. It involves four treatment cycles with possible dose adjustments based on individual responses and will compare progression-free survival at one year.

How Is the Trial Designed?

Group I: Lutetium-177 Octreotate Experimental Treatment 1 Intervention

Lutetium-177 Octreotate 200 mCi (7.4 GBq) by IV for 18-30 weeks

Lutetium-177 Octreotate is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Lutathera for:

• Unresectable or metastatic, progressive, well differentiated (G1 and G2), somatostatin receptor positive gastroenteropancreatic neuroendocrine tumours (GEP-NETs) in adults

Approved in United States as Lutathera for:

• Somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults

Approved in Canada as Lutathera for:

• Gastroenteropancreatic NETs

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Ozmosis Research Inc.

Industry Sponsor

Trials

25

Recruited

5,200+

Canadian Molecular Imaging Probe Consortium

Collaborator

Trials

1

Recruited

200+

Cancer Care Ontario

Collaborator

Trials

17

Recruited

92,000+

Published Research Related to This Trial

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]

Incorporating DTPA with (177)Lu-DOTA(0),Tyr(3)octreotate before administration significantly reduces the accumulation of free (177)Lu(3+) in bones, which can cause unwanted radiation exposure to bone marrow.

The study demonstrated that (177)Lu-DTPA has rapid renal clearance and lower total body retention compared to (177)LuCl(3), suggesting it is a safer option for managing free (177)Lu(3+) in peptide receptor-targeted radionuclide therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The addition of DTPA to [177Lu-DOTA0,Tyr3]octreotate prior to administration reduces rat skeleton uptake of radioactivity. Breeman, WA., van der Wansem, K., Bernard, BF., et al.[2019]

In a study involving seven patients with neuroendocrine tumors, the peptide [(177)Lu-DOTA(0),Tyr(3)]octreotate ((177)Lu-DOTATATE) demonstrated a longer residence time in tumors compared to [(177)Lu-DOTA(0),Tyr(3)]octreotide ((177)Lu-DOTATOC), suggesting it may be more effective for peptide receptor radionuclide therapy (PRRT).

Although (177)Lu-DOTATATE resulted in longer residence times in the kidneys, the overall tumor dose was still higher, making (177)Lu-DOTATATE the preferred choice for PRRT despite potential kidney dose concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of [(177)Lu-DOTA(0),Tyr(3)]octreotate and [(177)Lu-DOTA(0),Tyr(3)]octreotide: which peptide is preferable for PRRT? Esser, JP., Krenning, EP., Teunissen, JJ., et al.[2019]

The development of a single vial kit for (177) Lu-DOTATATE allows for safe and efficient preparation of this radiopharmaceutical in hospital settings, making it more accessible for treating patients with inoperable neuroendocrine tumors.

Preclinical studies showed that (177) Lu-DOTATATE is rapidly cleared from the body through the kidneys, indicating a favorable biodistribution profile that supports its use in peptide receptor radionuclide therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single vial kit formulation of DOTATATE for preparation of (177) Lu-labeled therapeutic radiopharmaceutical at hospital radiopharmacy. Mukherjee, A., Lohar, S., Dash, A., et al.[2019]

The study developed and validated a high-performance liquid chromatography (HPLC) method for quality control of the radiopeptide [177Lu]Lu-DOTA-TATE, ensuring its radiochemical purity meets therapeutic standards (95-105% of label claim).

The HPLC method demonstrated accuracy, precision, and sensitivity, making it suitable for clinical samples, which is crucial for the safe and effective use of [177Lu]Lu-DOTA-TATE in treating neuroendocrine tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The development and validation of a high performance liquid chromatography method to determine the radiochemical purity of [177Lu]Lu-HA-DOTA-TATE in pharmaceutical preparations. van Andel, L., Aalbersberg, EA., Geluk-Jonker, MM., et al.[2021]

177Lu-octreotate therapy showed potential effectiveness in treating paragangliomas and meningiomas, with some patients experiencing tumor regression or stable disease, although response rates were lower than in gastroenteropancreatic neuroendocrine tumors.

The treatment did not demonstrate any antitumor effects in patients with small cell lung carcinoma or melanoma, highlighting the need for further studies to confirm these findings due to the small patient sample size.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of therapy with [177Lu-DOTA0, Tyr3]octreotate in patients with paraganglioma, meningioma, small cell lung carcinoma, and melanoma. van Essen, M., Krenning, EP., Kooij, PP., et al.[2013]

Treatment with (177)Lu-DOTATATE, a radiolabelled somatostatin analogue, shows promising results in managing inoperable or metastasized neuroendocrine tumors, with significant tumor regression and a median progression-free survival of over 40 months.

The therapy is associated with few and mild side effects, especially when kidney-protective agents are used, and it significantly improves patients' quality of life, suggesting it could become a first-choice treatment option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lutetium-labelled peptides for therapy of neuroendocrine tumours. Kam, BL., Teunissen, JJ., Krenning, EP., et al.[2022]

In a phase 2 clinical trial involving 37 patients with progressive gastroenteropancreatic neuroendocrine tumors, treatment with Lutetium (177) DOTATATE showed that 28% of patients had a partial response and 41% had stable disease, indicating effective disease control.

The therapy was well tolerated with no significant acute or delayed toxicity observed, and it led to improvements in patients' performance status and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peptide receptor radionuclide therapy with 177Lu-DOTATATE for patients with somatostatin receptor-expressing neuroendocrine tumors: the first US phase 2 experience. Delpassand, ES., Samarghandi, A., Zamanian, S., et al.[2022]

Citations

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

Neuroendocrine Tumor 177Lutetium-Dotatate Therapy - NCBI Clinical trials, including the landmark NETTER-1 study, have demonstrated significant improvements in progression-free survival, quality of life ...

2. jnm.snmjournals.org jnm.snmjournals.org/content/early/2025/06/05/jnumed.124.269416

Cost-Effectiveness of [177Lu]Lu-DOTATATE for the Treatment ... Conclusion: [177Lu]Lu-DOTATATE is cost-effective as a first-line treatment for patients with grade 2 or 3, well-differentiated, advanced ...

3. 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 ...

4. 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.

5. lutathera-hcp.com lutathera-hcp.com/1l-netter-2-efficacy

1L: NETTER-2 | LUTATHERA® (lutetium Lu 177 dotatate) | HCP 43% overall response rate for LUTATHERA plus 30 mg octreotide, which is 4x greater. Duration of Response ...

6. lutathera-hcp.com lutathera-hcp.com/

LUTATHERA® (lutetium Lu 177 dotatate): GEP-NET Treatment Access HCP information about LUTATHERA, a treatment for SSTR+ gastroenteropancreatic neuroendocrine tumors (GEP-NETs). See full Prescribing and Safety Info.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04665739

NCT04665739 | Testing Lutetium Lu 177 Dotatate in ... Lutetium Lu 177 dotatate may be more effective than everolimus in shrinking or stabilizing advanced bronchial neuroendocrine tumors. Detailed Description.

8. onclive.com onclive.com/view/lutetium-lu-177-dotatate-yields-partial-responses-in-metastatic-bronchopulmonary-neuroendocrine-tumors

Lutetium Lu 177 Dotatate Yields Partial Responses in ... Real-world data showed that lutetium Lu 177 dotatate led to partial responses in patients with metastatic bronchopulmonary neuroendocrine tumors ...

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40310018/

Post-marketing Safety Evaluation of Lutathera ( 177 Lu- ... This study aims to conduct a comprehensive analysis of the adverse events (AEs) associated with Lutathera using FDA Adverse Event Reporting System (FAERS) data.