Lu-DOTA-TATE for Neuroendocrine Carcinoma

Overseen By NET Coordinator

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: AHS Cancer Control Alberta

Must be taking: Somatostatin analogues

Must not be taking: mTOR inhibitors, Tyrosine kinase inhibitors

Disqualifiers: Uncontrolled diabetes, Brain metastases, 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

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

Compensation: Varies

Number of Visits: 13

500 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called Lu-DOTA-TATE, a type of targeted radiotherapy for patients with certain neuroendocrine tumors (NETs). The researchers aim to evaluate the treatment's effectiveness, safety, and potential to improve quality of life and survival. Individuals with neuroendocrine tumors that appear on specific imaging tests and have symptoms not controlled by current treatments might be suitable for this study. As a Phase 2 trial, this research focuses on assessing 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, certain treatments like mTOR inhibitors, tyrosine kinase inhibitors, chemotherapy, and interferon must not have been used within specific time frames before joining the trial.

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

Research has shown that Lutetium-177 Octreotate (Lu-DOTA-TATE) is generally safe for patients. In previous studies, patients with neuroendocrine tumors (NETs) who received Lu-DOTA-TATE experienced positive outcomes. Specifically, their cancer remained stable for a longer period compared to other treatments.

One study found that even if a patient's condition worsened, receiving Lu-DOTA-TATE again remained safe, with most patients not experiencing severe side effects. This treatment has been used in Europe and North America for some time, and a brand called Lutathera is approved in several countries.

Overall, past trials have demonstrated the safety of Lu-DOTA-TATE, making it a viable option for those considering participation in a study. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for neuroendocrine tumours?

Unlike the standard treatments for neuroendocrine carcinoma, which typically involve chemotherapy or targeted therapies like everolimus and sunitinib, Lutetium-177 Octreotate (Lu-DOTA-TATE) offers a novel approach. This treatment is a type of peptide receptor radionuclide therapy (PRRT) that delivers radiation directly to the tumor cells by targeting somatostatin receptors, which are often overexpressed in these cancers. This targeted delivery not only maximizes the impact on cancer cells but also minimizes damage to surrounding healthy tissues. Researchers are excited about Lu-DOTA-TATE because it could potentially lead to better outcomes with fewer side effects compared to traditional treatments.

What is the effectiveness track record for Lutetium-177 Octreotate in treating neuroendocrine carcinoma?

Research has shown that Lutetium-177 Octreotate, or Lu-DOTA-TATE, yields promising results for treating neuroendocrine tumors (NETs). In earlier studies, patients treated with Lu-DOTA-TATE experienced longer progression-free survival. The NETTER-1 study found that patients receiving this treatment enjoyed a better quality of life. Another study revealed that 43% of patients experienced tumor shrinkage or disappearance. This trial will evaluate Lu-DOTA-TATE therapy, which could effectively manage NETs, particularly those that are advanced or resistant to other treatments. ^{1 2 3 6 7}

Who Is on the Research Team?

Donald W Morrish, MD, PhD

Principal Investigator

Professor of Endocrinology and Oncology, University of Alberta, Cross Cancer Institute

Are You a Good Fit for This Trial?

This trial is for individuals with neuroendocrine tumors, aged 14-90, who have a life expectancy of more than 12 weeks and are physically able to perform daily activities (ECOG ≤2). They must have somatostatin receptor positive tumors confirmed by imaging and meet specific blood test criteria. Those previously treated with Lu-DOTA-TATE or having certain medical conditions are excluded.

Inclusion Criteria

I have previously received Lu-DOTA-TATE treatment.

My liver is functioning well, and my blood protein levels are normal.

I have a confirmed diagnosis of a neuroendocrine tumor.

Exclusion Criteria

Group A (Primary Therapy): Another significant medical, psychiatric or surgical condition uncontrolled by treatment

Group A (Primary Therapy): Breast feeding

Group A (Primary Therapy): Pregnancy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Induction Treatment

Participants receive Lu-DOTA-TATE every 10-14 weeks for up to 4 treatments. An amino acid solution is infused prior to and during the Lu-DOTA-TATE infusion to protect the kidneys.

40-56 weeks

4 visits (in-person)

Maintenance Treatment

Participants with stable or improving disease status continue to receive Lu-DOTA-TATE every 22-40 weeks, up to a maximum of 8 treatments.

176-320 weeks

Up to 8 visits (in-person)

Follow-up

Participants are monitored for progression-free survival and overall survival at 6 months, 1 year, 2 years, 3 years, and 5 years after the last treatment.

5 years

Periodic visits (in-person and virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Lutetium-177 Octreotate

Trial Overview [177]Lu-DOTA-TATE therapy is being tested for its effectiveness in treating neuroendocrine tumors and its impact on patients' quality of life and survival. The study will also evaluate the safety of this treatment which has been used under special access but now requires clinical trial assessment.

How Is the Trial Designed?

Group I: [177]Lu-DOTA-TATE Therapy Experimental Treatment 1 Intervention

Nominal, induction stage dose of 150 mCi (5.55 GBq) \[177\]Lu-DOTA-TATE every 10 - 14 weeks for 4 treatments. Nominal maintenance stage dose of 100 mCi (3.7 GBq) \[177\]Lu-DOTA-TATE every 22 - 40 weeks, up to a maximum of 8 treatments.

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?

AHS Cancer Control Alberta

Lead Sponsor

Trials

188

Recruited

26,900+

Published Research Related to This Trial

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]

A 60-year-old woman with a metastatic neuroendocrine tumor showed a partial response after 4 cycles and a complete response after 2 additional maintenance cycles of (177)Lu DOTATATE therapy, indicating its efficacy in treating such tumors.

This case suggests that maintenance therapy with (177)Lu DOTATATE could enhance treatment outcomes for patients with neuroendocrine tumors, warranting further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complete Resolution of Neuroendocrine Tumor Soft Tissue Metastases After 177Lu DOTATATE PRRT Induction and Maintenance Therapy. Makis, W., McCann, K., Buteau, FA., 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]

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]

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]

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]

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]

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]

Salvage treatment with [177Lu-DOTA,Tyr3]octreotate is effective and safe for patients with progressive bronchial neuroendocrine tumors (NET) or gastroenteropancreatic NET (GEP-NET), showing a median overall survival of 80.8 months after initial treatment.

The treatment resulted in low rates of severe side effects, with only 6.6% and 7.7% of patients experiencing grade III/IV bone marrow toxicity after re-treatment and re-re-treatment, respectively, and no cases of severe kidney toxicity were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salvage peptide receptor radionuclide therapy with [177Lu-DOTA,Tyr3]octreotate in patients with bronchial and gastroenteropancreatic neuroendocrine tumours. van der Zwan, WA., Brabander, T., Kam, BLR., et al.[2020]

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. 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. 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 ...

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

Cost-Effectiveness of [177Lu]Lu-DOTATATE for the Treatment ... The NETTER-2 trial found superior median progression-free survival (22.8 mo vs. 8.5 mo) and similar adverse events and quality-of-life measures ...

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

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

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

Effectiveness and Safety of Retreatment with 177Lu ... Retreatment with 177 Lu-DOTATATE after progression appeared to be well tolerated and offered disease control in patients with progressive NETs after initial ...

7. 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 ... Lutetium Lu 177 dotatate demonstrated antitumor activity in metastatic BP-NETs, with partial responses in 17% of patients and stable disease in ...