PRRT for Neuroendocrine Tumors

(COMPETE Trial)

Recruiting at 56 trial locations

Overseen By Amanda Rotger, Dr

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: ITM Solucin GmbH

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

309 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of the study is to evaluate efficacy and safety of Peptide Receptor Radionuclide Therapy (PRRT) with 177Lu-Edotreotide compared to targeted molecular therapy with Everolimus in patients with inoperable, progressive, somatostatin receptor-positive (SSTR+), neuroendocrine tumours of gastroenteric or pancreatic origin (GEP-NET).

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.

What data supports the effectiveness of the treatment 177Lu-edotreotide PRRT, Everolimus, Afinitor, Votubia, Zortress for neuroendocrine tumors?

Research shows that combining everolimus with 177Lu-DOTATATE (a similar treatment to 177Lu-edotreotide PRRT) can help control neuroendocrine tumors, with some patients experiencing stable disease and a median progression-free survival of 23.3 months. Additionally, 177Lu-DOTATATE alone has been shown to improve quality of life and progression-free survival in patients with neuroendocrine neoplasms. ^{1 2 3 4 5}

Is PRRT with 177Lu-DOTATATE and everolimus safe for treating neuroendocrine tumors?

The combination of everolimus and 177Lu-DOTATATE has shown some safety concerns, with common mild side effects like mouth sores and nausea, and more serious side effects like fatigue and infections in some patients. A larger trial with a lower dose of everolimus is suggested to better understand its safety. ^{1 2 4 5 6}

How is the treatment 177Lu-edotreotide PRRT with Everolimus different from other treatments for neuroendocrine tumors?

This treatment combines 177Lu-edotreotide PRRT, which targets and delivers radiation directly to tumor cells, with Everolimus, a drug that helps slow tumor growth by blocking a specific protein pathway. This combination aims to enhance treatment effectiveness compared to using either approach alone. ^{5 7 8 9 10}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

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

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

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

Peptide Receptor Radionuclide Therapy With 177Lu-DOTATATE for Symptomatic Control of Refractory Carcinoid Syndrome. [2021]

3. England pubmed.ncbi.nlm.nih.gov

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

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

Efficacy of Everolimus Combined with 177Lu-Dotatate in the Treatment of Neuroendocrine Tumors. [2022]

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

Peptide Receptor Radionuclide Therapy for Patients With Advanced Lung Carcinoids. [2020]

6. Germany 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. [2023]

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

Strategies Towards Improving Clinical Outcomes of Peptide Receptor Radionuclide Therapy. [2021]

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

Long-term survival and toxicity in patients with neuroendocrine tumors treated with 177 Lu-octreotate peptide radionuclide therapy. [2022]

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

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

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

Radiolabeled Somatostatin Analogue Therapy Of Gastroenteropancreatic Cancer. [2022]