PRRT for Neuroendocrine Tumors

(COMPOSE Trial)

Not currently recruiting at 45 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called 177Lu-Edotreotide, a type of peptide receptor radionuclide therapy (PRRT), for individuals with certain neuroendocrine tumors. These tumors originate in hormone-producing cells in the gut or pancreas. The trial aims to determine if this treatment is more effective and safer than usual care options. Participants are divided into two groups: one receives the experimental treatment, while the other receives standard treatments like chemotherapy. Candidates include those with neuroendocrine tumors that cannot be surgically removed and have specific receptors (somatostatin receptors). As a Phase 3 trial, this study represents the final step before FDA approval, providing access to potentially groundbreaking treatment.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that 177Lu-Edotreotide, a treatment for neuroendocrine tumors, is generally well-tolerated by patients. Previous studies found few serious side effects, with most being mild and manageable, such as nausea, fatigue, and minor changes in blood counts. This treatment is similar to 177Lu-DOTATATE, which is already approved for other uses, providing some confidence in its safety for new patients. Patients should always consult their doctor with any concerns. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for neuroendocrine tumors?

177Lu-Edotreotide is unique because it uses a targeted approach known as Peptide Receptor Radionuclide Therapy (PRRT) to treat neuroendocrine tumors. This method delivers a radioactive substance directly to cancer cells by binding to specific receptors, which can lead to more effective tumor destruction while sparing healthy tissue. Unlike traditional chemotherapy or other systemic treatments, PRRT specifically targets tumor cells, potentially reducing side effects and improving patient outcomes. Researchers are excited because this precision targeting could represent a significant advancement in treating neuroendocrine tumors, offering a new hope for patients who may not respond well to conventional therapies.

What evidence suggests that this trial's treatments could be effective for neuroendocrine tumors?

Research has shown that 177Lu-Edotreotide, which participants may receive in the Peptide Receptor Radionuclide Therapy (PRRT) Arm, holds promise for treating neuroendocrine tumors. Studies have found that this treatment can extend the lives of patients with advanced or hard-to-remove neuroendocrine tumors and slow the disease's progression. It proves particularly effective for patients with more aggressive tumors, known as grade 2 or 3, making it a strong choice for initial treatment. This therapy targets specific parts of the tumor cells, delivering radiation directly to the cancer, which can help stop its growth. This targeted approach has demonstrated positive results, offering hope for better management of this condition. ^{2 3 6 7 8}

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 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]

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]

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]

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]

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]

Citations

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

Neuroendocrine Tumor 177Lutetium-Dotatate Therapy - NCBI Implement 177Lu-dotatate therapy to improve overall survival and progression-free survival in adults with unresectable, advanced, or well or ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04919226

NCT04919226 | Lutetium 177Lu-Edotreotide Versus Best ... The purpose of the study is to evaluate the efficacy, safety & patient-reported outcomes of peptide receptor radionuclide therapy (PRRT) with 177Lu-Edotreotide ...

3. itm-radiopharma.com itm-radiopharma.com/news/press-releases/press-releases-detail/itm-presents-positive-topline-phase-3-compete-trial-data-with-nca-177lu-edotreotide-itm-11-a-targeted-radiopharmaceutical-therapy-in-patients-with-grade-1-or-2-gastroenteropancreatic-neuroendocrine-tumors-at-the-enets-2025-conference-688/

Press Release The trial results demonstrated that nca 177 Lu-edotreotide (also known as ITM-11 or 177 Lu-edotreotide), a proprietary, synthetic, targeted radiotherapeutic ...

4. 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 ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12560366/

177 DOTATATE Peptide Receptor Radionuclide Therapy ... Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine tumors in the united States. JAMA Oncol. 2017;3 ...

6. jnm.snmjournals.org jnm.snmjournals.org/content/66/3/449

Dosimetry of [177Lu]Lu-DOTATATE in Patients with ... Long-term efficacy, survival, and safety of [177Lu-DOTA0,Tyr3]octreotate in patients with gastroenteropancreatic and bronchial neuroendocrine ...

7. itm-radiopharma.com itm-radiopharma.com/news/press-releases/press-releases-detail/itm-presents-dosimetry-data-from-phase-3-compete-trial-supporting-favorable-efficacy-and-safety-profile-with-n-c-a-177lu-edotreotide-itm-11-in-patients-with-gastroenteropancreatic-neuroendocrine-tumors-at-eanm-2025-annual-congress-739/

Press Release ITM Presents Dosimetry Data from Phase 3 COMPETE Trial Supporting Favorable Efficacy and Safety Profile with n.c.a. 177Lu-edotreotide (ITM-11) ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.4604

Safety of 177Lu-DOTATATE in patients with advanced ... In a real-world population of US patients with advanced GEPNETs, 177 Lu-DOTATATE treatment was well tolerated with few TRAEs, consistent with the safety ...