Lu-DOTATATE for Neuroendocrine Cancer

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

195 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing a targeted radiation therapy called Lutetium-177 Octreotate in patients with advanced neuroendocrine tumors that have specific receptors. The treatment aims to deliver radiation directly to the cancer cells to stop their growth. Patients will receive multiple treatment cycles, and their progress will be monitored over time. Lutetium-177 Octreotate was approved by the FDA in January 2018 for treating certain types of neuroendocrine tumors.

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.

Is Lu-DOTATATE generally safe for humans?

Lu-DOTATATE has been used as a treatment for neuroendocrine tumors and is generally considered safe, but it can have side effects. Some studies have shown that it is well-tolerated, but there can be issues like unwanted radiation exposure to bones if not properly managed. Adding certain substances can help reduce these risks. ^{1 2 3 4 5}

What makes the drug Lu-DOTATATE unique for treating neuroendocrine cancer?

Lu-DOTATATE is unique because it uses a radioactive component to target and bind to specific receptors on neuroendocrine tumor cells, delivering radiation directly to the cancer cells while minimizing damage to surrounding healthy tissue. This targeted approach can lead to significant tumor regression and improved quality of life with fewer side effects compared to other treatments. ^{1 3 4 6 7}

What data supports the effectiveness of the treatment Lutetium-177 DOTATATE for neuroendocrine cancer?

Research shows that Lutetium-177 DOTATATE is effective for treating neuroendocrine tumors, as it has been used successfully in patients with these types of tumors, including those with metastasized or inoperable conditions. Studies have demonstrated its early efficacy and manageable toxicity in patients with progressive metastatic neuroendocrine tumors. ^{1 2 3 6 8}

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

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. Netherlands 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. [2021]

2. United States 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. [2022]

3. Germany 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? [2019]

4. England pubmed.ncbi.nlm.nih.gov

Early efficacy of and toxicity from lutetium-177-DOTATATE treatment in patients with progressive metastatic NET. [2019]

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

Effects of therapy with [177Lu-DOTA0, Tyr3]octreotate in patients with paraganglioma, meningioma, small cell lung carcinoma, and melanoma. [2013]

6. England pubmed.ncbi.nlm.nih.gov

Single vial kit formulation of DOTATATE for preparation of (177) Lu-labeled therapeutic radiopharmaceutical at hospital radiopharmacy. [2019]

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

The addition of DTPA to [177Lu-DOTA0,Tyr3]octreotate prior to administration reduces rat skeleton uptake of radioactivity. [2019]

8. Germany pubmed.ncbi.nlm.nih.gov

Lutetium-labelled peptides for therapy of neuroendocrine tumours. [2022]