PRRT for Neuroendocrine Tumors

(COMPOSE Trial)

Recruiting at 42 trial locations

Overseen By Serhii Melnyk

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: ITM Solucin GmbH

Disqualifiers: Other malignancies, Serious diseases, Organ dysfunction, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 12

Duration: 12 weeks

259 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing a new treatment that uses a radioactive drug to target and kill specific cancer cells in patients with certain types of neuroendocrine tumors. It aims to see if this method is more effective and safer than current treatments.

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

The trial information does not specify if you need to stop taking your current medications. However, if you are on an investigational drug, you must stop it at least 30 days before joining the trial.

Is 177Lu-Edotreotide PRRT generally safe for humans?

177Lu-Edotreotide PRRT is generally considered safe, but it can have side effects like potential toxicity to the kidneys, liver, and blood cells, and there is a risk of developing a second cancer. These side effects have been observed in studies, even though the treatment is effective for certain types of tumors. ^{1 2 3 4 5}

How is the treatment 177Lu-Edotreotide different from other treatments for neuroendocrine tumors?

177Lu-Edotreotide is a type of peptide receptor radionuclide therapy (PRRT) that uses a radioactive substance to target and bind to specific receptors on neuroendocrine tumor cells, delivering radiation directly to the tumor. This approach is unique because it combines a targeted delivery system with radiation therapy, potentially offering a more focused treatment with fewer side effects compared to traditional chemotherapy. ^{1 5 6 7 8}

What data supports the effectiveness of the treatment 177Lu-Edotreotide for neuroendocrine tumors?

Research shows that a similar treatment, 177Lu-DOTATATE, is effective for neuroendocrine tumors that express somatostatin receptors, providing symptomatic and radiological improvements in patients with inoperable or metastatic tumors. ^{1 2 5 8 9}

Are You a Good Fit for This Trial?

This trial is for adults with aggressive, well-differentiated GEP-NETs that can't be surgically removed and have shown up on scans. Participants must have tumors with somatostatin receptors but cannot join if they're pregnant, breastfeeding, hypersensitive to the drugs being tested, recently had major surgery or other cancer treatments, or have serious health issues affecting their organs.

Inclusion Criteria

My GEP-NETs cancer is confirmed and can't be removed by surgery.

My condition is positive for somatostatin receptors.

Exclusion Criteria

Pregnant or breastfeeding women

I am allergic to Lutetium 177Lu or related substances.

I have had Peptide Receptor Radionuclide Therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Peptide Receptor Radionuclide Therapy (PRRT) with 177Lu-Edotreotide or best standard of care

12 weeks

Every 12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• 177Lu-Edotreotide
• Everolimus

Trial Overview The COMPOSE study is testing whether a treatment called 177Lu-Edotreotide (a type of PRRT) works better as a first or second option compared to standard therapies like CAPTEM, Everolimus, FOLFOX for certain neuroendocrine tumors. Patients will either receive this new therapy or one of the established treatments.

How Is the Trial Designed?

Group I: Peptide Receptor Radionuclide Therapy (PRRT) Arm Experimental Treatment 2 Interventions

Group II: CAPTEM(Capecitabine-Temozolomide), Everolimus, FOLFOX(Folinic acid + Fluorouracil + Oxaliplatin) Active Control 3 Interventions

177Lu-Edotreotide is already approved in European Union, United States for the following indications:

Approved in European Union as Solucin for:

• Gastroenteropancreatic neuroendocrine tumors (GEP-NETs)

Approved in United States as ITM-11 for:

• Gastroenteropancreatic neuroendocrine tumors (GEP-NETs)

Who Is Running the Clinical Trial?

ITM Solucin GmbH

Lead Sponsor

Trials

3

Recruited

580+

Published Research Related to This Trial

Peptide receptor radionuclide therapy (PRRT) using 177Lu-DOTATATE is effective for treating metastatic functioning pancreatic neuroendocrine tumors (pNETs), with 59% of patients showing partial or complete response and a disease control rate of 78%.

While the treatment is generally safe, with only 12% experiencing severe hematological toxicity, hormonal crises occurred in 9% of patients, suggesting the need for preventive measures during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Symptomatic and Radiological Response to 177Lu-DOTATATE for the Treatment of Functioning Pancreatic Neuroendocrine Tumors. Zandee, WT., Brabander, T., Blažević, A., et al.[2020]

In a study of 143 patients with somatostatin-expressing neuroendocrine tumors, treatment with Lu-DOTATATE showed no significant increase in toxicity for patients with a history of regional chemoembolization and radionuclide hepatic embolization (CRHE).

Patients with a history of CRHE had a statistically significant higher rate of stable disease and lower rates of disease progression after Lu-DOTATATE therapy, indicating that prior CRHE is not a contraindication for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Effectiveness of 177Lu-DOTATATE Peptide Receptor Radionuclide Therapy After Regional Hepatic Embolization in Patients With Somatostatin-Expressing Neuroendocrine Tumors. Hamiditabar, M., Ali, M., Bolek, L., et al.[2022]

Peptide receptor radionuclide therapy (PRRT) using [177Lu]Lu-DOTATATE has been shown to be effective and safe for treating neuroendocrine neoplasms (NENs) across various tumor locations, with a median progression-free survival of up to 31.3 months for midgut tumors.

In a study of 522 patients, the treatment resulted in a partial response in 33.2% of cases and stable disease in 52.1%, indicating significant clinical benefit with minimal severe toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of [177Lu]Lu-DOTATATE in metastatic neuroendocrine neoplasms of different locations: data from the SEPTRALU study. Mitjavila, M., Jimenez-Fonseca, P., Belló, P., et al.[2023]

In a study of 144 patients with metastatic neuroendocrine tumors, Lu DOTATATE therapy demonstrated a cumulative disease control rate of 59.09%, indicating it can effectively manage tumor progression in this patient population.

The therapy was found to be safe, with no grade 3 or 4 renal toxicities reported, although some patients experienced grade 3 and 4 hematological and hepatotoxic adverse events, which were generally manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peptide Receptor Radionuclide Therapy With 177Lu-Octreotate in Patients With Somatostatin Receptor Expressing Neuroendocrine Tumors: Six Years' Assessment. Hamiditabar, M., Ali, M., Roys, J., et al.[2020]

Lutetium-177 (Lu-177) DOTATATE is an effective treatment for inoperable gastroenteropancreatic neuroendocrine tumors (GEP-NETs) that have not responded to standard therapies, as it can reduce tumor size, improve symptoms, and increase progression-free survival.

The practice parameter document ensures safe handling and administration of Lu-177 DOTATATE, providing essential guidelines for authorized users to maintain consistent and safe treatment practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ACR-ACNM-ASTRO-SNMMI Practice Parameter for Lutetium-177 (Lu-177) DOTATATE Therapy. Love, C., Desai, NB., Abraham, T., et al.[2023]

Peptide receptor radionuclide therapy (PRRT) with lutetium-177 (Lu)-DOTATATE is a safe and effective treatment for patients with inoperable or metastatic neuroendocrine neoplasia (NEN), showing a clinical response of regressive disease in 47.6% of cases.

The study found no severe renal or hematological toxicity in 30 patients treated with Lu-DOTATATE, suggesting that while hematological parameters may influence survival, the treatment itself is well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peptide receptor radionuclide therapy with 177Lu-DOTA-octreotate: dosimetry, nephrotoxicity, and the effect of hematological toxicity on survival. Löser, A., Schwarzenböck, SM., Heuschkel, M., et al.[2018]

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]

Peptide Receptor Radionuclide Therapy (PRRT) is an effective treatment for patients with inoperable or metastatic neuroendocrine tumors (NETs), showing progression-free survival and overall survival rates comparable to standard therapies.

The therapy utilizes a somatostatin-modified peptide fragment that binds to β-emitting radionuclides like yttrium-90 and lutetium-177, which have been successfully applied in humans over the past 25 years, demonstrating significant therapeutic potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

90Y/177Lu-DOTATOC: From Preclinical Studies to Application in Humans. Uccelli, L., Boschi, A., Cittanti, C., et al.[2021]

177Lu peptide receptor radionuclide therapy (PRRT) is a well-tolerated treatment for advanced gastroenteropancreatic neuroendocrine tumors, with a median overall survival of 12.5 months observed in a study of 36 patients over a follow-up period of 3 years.

The effectiveness of PRRT is influenced by factors such as previous treatment toxicity, tumor grade, and the presence of bone metastases, with better outcomes associated with successful surgeries of the primary tumor and metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of 177Lu-Dotatate treatment in patients with metastatic neuroendocrine tumors and prognostic factors. Abou Jokh Casas, E., Pubul Núñez, V., Anido-Herranz, U., et al.[2021]

Citations

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

Symptomatic and Radiological Response to 177Lu-DOTATATE for the Treatment of Functioning Pancreatic Neuroendocrine Tumors. [2020]

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

Safety and Effectiveness of 177Lu-DOTATATE Peptide Receptor Radionuclide Therapy After Regional Hepatic Embolization in Patients With Somatostatin-Expressing Neuroendocrine Tumors. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Efficacy of [177Lu]Lu-DOTATATE in metastatic neuroendocrine neoplasms of different locations: data from the SEPTRALU study. [2023]

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

Peptide Receptor Radionuclide Therapy With 177Lu-Octreotate in Patients With Somatostatin Receptor Expressing Neuroendocrine Tumors: Six Years' Assessment. [2020]

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

ACR-ACNM-ASTRO-SNMMI Practice Parameter for Lutetium-177 (Lu-177) DOTATATE Therapy. [2023]

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

Peptide receptor radionuclide therapy with 177Lu-DOTA-octreotate: dosimetry, nephrotoxicity, and the effect of hematological toxicity on survival. [2018]

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

Lutetium Lu-177 Dotatate Flare Reaction. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

90Y/177Lu-DOTATOC: From Preclinical Studies to Application in Humans. [2021]

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

Evaluation of 177Lu-Dotatate treatment in patients with metastatic neuroendocrine tumors and prognostic factors. [2021]