PRRT for Neuroendocrine Tumors

(COMPETE Trial)

Not currently recruiting at 61 trial locations

Overseen By Amanda Rotger, Dr

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: ITM Solucin GmbH

Must not be taking: mTor inhibitors, others

Disqualifiers: Hypersensitivity, Prior PRRT, Serious disease, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 9 months for PRRT, continuous for Everolimus

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines two treatments for neuroendocrine tumors that cannot be surgically removed and continue to grow. One treatment, PRRT (Peptide Receptor Radionuclide Therapy), uses a radioactive drug to target tumor cells, while the other is a daily pill called Everolimus. The study aims to determine which treatment is more effective and safer for patients. Suitable participants have neuroendocrine tumors in the stomach, intestines, or pancreas that test positive for a specific protein (somatostatin receptor). As a Phase 3 trial, this research represents the final step before FDA approval, offering patients a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on investigational drugs or certain therapies like mTor inhibitors, you may need to stop those 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 PRRT is generally safe. In studies, patients experienced fewer side effects compared to those taking everolimus, another treatment option, indicating that 177Lu-edotreotide is usually well-tolerated.

Everolimus, already used for other conditions, has known and manageable side effects. Common side effects include mouth sores and fatigue, but many patients can continue treatment without major issues.

Overall, both treatments have undergone safety testing, with 177Lu-edotreotide demonstrating fewer side effects in comparisons. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about 177Lu-edotreotide PRRT because it offers a targeted approach to treating neuroendocrine tumors. Unlike standard treatments like surgery or chemotherapy, which can affect healthy cells, 177Lu-edotreotide PRRT specifically delivers radiation to tumor cells using a molecule that binds to them, potentially reducing side effects. Additionally, everolimus, another treatment in the trial, works by inhibiting a protein that helps cancer cells grow, offering another method of targeting the tumors. These treatments provide new strategies that could improve outcomes for patients.

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

Research has shown that 177Lu-edotreotide PRRT, one of the treatments in this trial, is a promising option for neuroendocrine tumors. Specifically, studies demonstrated that this treatment extended the time patients lived without disease progression to 23.9 months, compared to 14.1 months with another treatment option in this trial, Everolimus. This suggests patients might experience a longer period without tumor growth. Earlier research also found that similar treatments achieved better results, with more tumors shrinking or halting growth. These findings suggest that 177Lu-edotreotide PRRT could be an effective option for patients with certain types of neuroendocrine tumors. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with certain types of neuroendocrine tumors in the digestive system or pancreas that can't be removed by surgery. Participants must have a confirmed diagnosis, measurable disease, positive somatostatin receptor status, and evidence of disease progression. They cannot have had certain prior treatments like mTor inhibitors or PRRT, nor can they be pregnant or unable to consent.

Inclusion Criteria

My cancer has grown despite treatment, confirmed by two scans.

My condition is positive for somatostatin receptors.

Measurable disease per RECIST 1.1

Exclusion Criteria

I have kidney, liver, heart, or blood issues that could affect my safety during the study.

I am allergic to certain cancer treatment drugs or their ingredients.

My doctor believes surgery could potentially cure my condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 177Lu-edotreotide PRRT or Everolimus. PRRT involves up to four cycles of 177Lu-edotreotide, each 90 days apart, while Everolimus is administered daily until progression or end of study.

9 months for PRRT, continuous for Everolimus

Follow-up

Participants are monitored for progression-free survival and overall survival, with assessments every 3 months.

30 months

What Are the Treatments Tested in This Trial?

Interventions

• 177Lu-edotreotide PRRT
• Everolimus

Trial Overview The study compares two treatments: Peptide Receptor Radionuclide Therapy (PRRT) using a radioactive drug called 177Lu-Edotreotide versus Everolimus, a targeted molecular therapy. The goal is to see which treatment is more effective and safer for patients with advanced neuroendocrine tumors.

How Is the Trial Designed?

Group I: 177Lu-edotreotide PRRT Experimental Treatment 2 Interventions

177Lu-edotreotide (177Lu-DOTATOC) A maximum of four cycles of 7.5 ± 0.7 GBq (gigabequerel) 177Lu-edotreotide, each. Route of administration: Slow intravenous infusion/injection (i.v.) Duration of treatment: 4 cycles, 90 days apart (total duration: 270 days/9 months)

Group II: Everolimus Active Control 1 Intervention

Everolimus (Afinitor ®) Doses: 10 mg/d Route of administration: Oral Duration of treatment: Continuous daily treatment until diagnosis of progression or End of Study (EOS)

Who Is Running the Clinical Trial?

ITM Solucin GmbH

Lead Sponsor

Trials

3

Recruited

580+

ABX CRO

Collaborator

Trials

6

Recruited

1,700+

PSI CRO

Industry Sponsor

Trials

13

Recruited

2,800+

Published Research Related to This Trial

Lu-DOTATATE demonstrated significantly better therapeutic efficacy in treating advanced pancreatic neuroendocrine tumors (pNETs) compared to Everolimus, with an objective response rate of 47% versus 12% and longer progression-free survival of 25.7 months compared to 14.7 months.

Lu-DOTATATE also had a superior safety profile, with fewer patients experiencing severe hematological toxicity (5% vs. 11%) and no treatment-related discontinuations, while Everolimus led to discontinuation in 59 out of 371 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

177Lu-DOTATATE peptide receptor radionuclide therapy versus Everolimus in advanced pancreatic neuroendocrine tumors: a systematic review and meta-analysis. Satapathy, S., Mittal, BR.[2023]

In a study of 22 patients with carcinoid syndrome, treatment with 177Lu-DOTATATE significantly reduced bowel movement frequency from an average of 6.1 to 4.6 per day and flushing episodes from 4.3 to 2.4 per day, indicating effective symptom relief.

The therapy also led to a notable decrease in urinary 5-hydroxyindolacetic acid excretion in 56% of patients, suggesting that 177Lu-DOTATATE can be a valuable option for managing symptoms in patients not adequately controlled by somatostatin analogs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peptide Receptor Radionuclide Therapy With 177Lu-DOTATATE for Symptomatic Control of Refractory Carcinoid Syndrome. Zandee, WT., Brabander, T., Blažević, A., 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]

The maximum tolerated dose of everolimus when combined with (177)Lu-octreotate therapy for advanced gastro-entero pancreatic neuroendocrine tumors is 7.5 mg daily, as higher doses led to significant side effects like neutropenia and thrombocytopenia.

The treatment combination showed a promising overall response rate of 44% among 16 patients, with no disease progression observed during the 6-month treatment period, indicating potential efficacy in managing these tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NeuroEndocrine Tumor Therapy with Lutetium-177-octreotate and Everolimus (NETTLE): A Phase I Study. Claringbold, PG., Turner, JH.[2022]

The combination of everolimus and PRRT (177Lu-DOTATATE) for treating advanced neuroendocrine tumors showed significant safety concerns, with 36% of patients experiencing grade 3 toxicities, including fatigue and infection, although no grade 4 toxicities were reported.

Despite some patients achieving stable disease and a median progression-free survival of 23.3 months, the trial was terminated early due to poor patient enrollment and treatment-related toxicities, suggesting that a lower dose of everolimus may be necessary for future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Everolimus Combined with 177Lu-Dotatate in the Treatment of Neuroendocrine Tumors. Aljubran, A., Badran, A., Alrowaily, M., et al.[2022]

In a study involving female Lewis rats, the combination of everolimus and [177Lu]Lu-DOTA-TATE did not increase renal or blood toxicity compared to [177Lu]Lu-DOTA-TATE alone, suggesting a safe combination therapy for neuroendocrine tumors.

Everolimus treatment resulted in lower creatinine levels, indicating better renal function, while it also significantly reduced white blood cell counts, highlighting its effects on blood health without exacerbating the side effects of PRRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity of a combined therapy using the mTOR-inhibitor everolimus and PRRT with [177Lu]Lu-DOTA-TATE in Lewis rats. Zellmer, J., Yen, HY., Kaiser, L., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03049189

NCT03049189 | Efficacy and Safety of 177Lu-edotreotide ... The purpose of the study is to evaluate efficacy and safety of Peptide Receptor Radionuclide Therapy (PRRT) with 177Lu-Edotreotide compared to targeted ...

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

177 DOTATATE Peptide Receptor Radionuclide Therapy ... The combination of PRRT and chemotherapy may enhance treatment efficacy by targeting both somatostatin receptor-positive and FDG-avid tumor ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.4_suppl.TPS514

Pivotal phase III COMPOSE trial will compare 177 Lu- ... This trial is to evaluate the efficacy, safety and patient-reported outcomes of first- or second-line treatment with 177 Lu-edotreotide PRRT compared to best ...

4. onclive.com onclive.com/view/177lu-edotreotide-radiopharmaceutical-therapy-prolongs-pfs-vs-everolimus-in-sstr-gep-nets

177Lu-edotreotide Radiopharmaceutical Therapy Prolongs ... 177Lu-edotreotide significantly extended PFS in GEP-NET patients compared to everolimus, with a median PFS of 23.9 months versus 14.1 months.

5. 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.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9516233/

Safety and efficacy of peptide receptor radionuclide ... In terms of efficacy, we observed a response rate of 33.3% and a disease control rate of 85.2% on RECIST criteria, and a response rate of 48.3% and a disease ...

7. targetedonc.com targetedonc.com/view/trial-data-shows-safety-and-efficacy-with-itm-11-in-patients-with-gep-nets

Trial Data Show Safety and Efficacy of ITM-11 in Patients ... Dosimetry data from a phase 3 clinical trial reveals favorable safety and efficacy with nca 177Lu-edotreotide (ITM-11) in patients with ...