Personalized PRRT for Neuroendocrine Tumors

(P-PRRT Trial)

Not currently recruiting at 1 trial location

Overseen By Geneviève Filion

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: CHU de Quebec-Universite Laval

Disqualifiers: Pregnancy, Breastfeeding, Limited survival, others

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

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

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to personalize a treatment called PRRT, which uses a radioactive drug, 177Lu-Octreotate, to target neuroendocrine tumors (NETs). Researchers seek to evaluate how effectively this personalized approach shrinks tumors, improves symptoms, and impacts survival rates. Understanding any side effects and their relation to the radiation dose received is also crucial. Suitable participants have progressive NETs that cannot be surgically removed and have not responded to other treatments. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to innovative cancer care.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that 177Lu-Octreotate, the treatment in this trial, is generally safe for people with neuroendocrine tumors. Studies have found that most patients tolerate this therapy well.

In one study, only one patient experienced serious kidney problems, indicating that severe side effects are rare. Another study demonstrated that patients receiving this treatment had longer periods without cancer progression compared to those on other treatments.

Additionally, long-term research confirms that this therapy is not only effective but also safe for treating advanced neuroendocrine tumors. While some side effects can occur, they are usually not severe.

Overall, evidence suggests that 177Lu-Octreotate is a reliable and safe option for many patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about 177Lu-Octreotate for neuroendocrine tumors because it offers a personalized approach to treatment. Unlike standard therapies, which often follow a one-size-fits-all method, this treatment tailors the dosage of radiation based on each patient's kidney function and previous cycles' responses. This personalization aims to maximize effectiveness while minimizing side effects. Additionally, 177Lu-Octreotate allows for adjustments if a patient has prior PRRT exposure, offering flexibility and potentially better outcomes for those with unique treatment histories.

What evidence suggests that personalized PRRT could be an effective treatment for neuroendocrine tumors?

Research shows that 177Lu-Octreotate, also known as LuTate, effectively treats neuroendocrine tumors. Studies have found that this treatment can help patients live longer without disease progression. Specifically, the NETTER-1 study found that patients receiving 177Lu-Octreotate responded better than those taking high-dose octreotide, another treatment option. Another study confirmed that this therapy is both effective and safe for patients with advanced or spreading neuroendocrine tumors. In this trial, participants will receive a personalized approach to 177Lu-Octreotate administration, potentially providing significant benefits for patients with these tumors. ^{2 6 7 8 9}

Who Is on the Research Team?

Jean-Mathieu Beauregard, MD,MSc,FRCPC

Principal Investigator

CHU de Québec - Université Laval

Are You a Good Fit for This Trial?

This trial is for patients with neuroendocrine tumors showing high levels of a specific receptor, who can't have or don't want surgery and haven't had success with other treatments. It's not for those with very short life expectancy, severe illness (ECOG 4), or pregnant/breastfeeding individuals.

Inclusion Criteria

My neuroendocrine tumor is growing or causing symptoms.

I cannot or do not want to use other available treatments for my condition.

My tumor shows high levels of a specific protein, confirmed by a special scan.

Exclusion Criteria

My doctors expect I have only a few weeks to live due to my condition.

Pregnancy

Breastfeeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Participants receive a four-cycle induction course of personalized PRRT with 177Lu-Octreotate (LuTate)

12 weeks

4 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Consolidation/Maintenance Treatment

Participants responding to the induction course may receive additional consolidation and/or maintenance cycles

What Are the Treatments Tested in This Trial?

Interventions

• 177Lu-Octreotate

Trial Overview

The study tests personalized doses of a radioactive drug called LuTate to treat neuroendocrine tumors effectively while minimizing harm to healthy organs. The goal is to improve survival rates and understand the relationship between radiation dose received by the tumor and patient outcomes.

How Is the Trial Designed?

Group I: Personalized PRRT (P-PRRT) Experimental Treatment 1 Intervention

177Lu-Octreotate (LuTate) P-PRRT will be administered as follows: * Renal absorbed radiation dose will be prescribed for the 4-cycle induction course (23 Gy) and for each subsequent cycle (6 Gy), with a reduction in cases of impaired renal or bone marrow function, or significant toxicity from prior cycles. * The personalized activity to be administered at each cycle will be derived from renal dose per unit of injected activity that is predicted by patient characteristics or renal dose delivered during prior cycle(s). * Participants responding to the induction course of P-PRRT will be eligible to receive additional consolidation and/or maintenance cycles. * Participants with prior PRRT exposure outside the trial may receive less induction cycles, or only consolidation/maintenance cycle(s).

Who Is Running the Clinical Trial?

CHU de Quebec-Universite Laval

Lead Sponsor

Trials

177

Recruited

110,000+

Published Research Related to This Trial

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]

In a study of 52 patients with advanced pancreatic neuroendocrine tumors, (177)Lu-DOTATATE therapy demonstrated significant antitumor activity, achieving an overall disease control rate of 81% with both full and reduced dosages.

Patients receiving the higher dosage of 27.8 GBq had a longer progression-free survival compared to those on the reduced dosage of 18.5 GBq, suggesting that the higher dose is more effective and is recommended for eligible patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment with the radiolabelled somatostatin analog Lu-DOTATATE for advanced pancreatic neuroendocrine tumors. Sansovini, M., Severi, S., Ambrosetti, A., et al.[2022]

In a study of 56 patients with advanced neuroendocrine tumors treated with (177)Lu-DOTATOC, the median progression-free survival was 17.4 months and overall survival was 34.2 months, indicating significant efficacy in managing these tumors.

The treatment demonstrated a favorable safety profile, with no serious adverse events reported and only one case of mild myelotoxicity, suggesting it is safe even for patients with pre-existing renal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[(177)Lu-DOTA](0)-D-Phe(1)-Tyr(3)-Octreotide ((177)Lu-DOTATOC) For Peptide Receptor Radiotherapy in Patients with Advanced Neuroendocrine Tumours: A Phase-II Study. Baum, RP., Kluge, AW., Kulkarni, H., et al.[2022]

In a study of 43 patients with advanced gastrointestinal neuroendocrine tumors, (177)Lu-Dotatate peptide receptor radionuclide therapy (Lu-PRRT) demonstrated an 84% disease control rate, with a median response duration of 25 months and a median progression-free survival of 36 months.

Both standard and reduced dosages of Lu-PRRT were found to be safe, as none of the patients experienced side effects, even those at higher risk for kidney or bone marrow toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

177 Lu-Dota-octreotate radionuclide therapy of advanced gastrointestinal neuroendocrine tumors: results from a phase II study. Paganelli, G., Sansovini, M., Ambrosetti, A., et al.[2022]

Peptide receptor radionuclide therapy (PRRT) using 177 Lu-DOTATATE has demonstrated significant efficacy in reducing the size of metastatic neuroendocrine tumors, achieving about a 20% reduction in lesions smaller than 3 cm.

In a specific case involving a 66-year-old man with a rapidly growing 10 cm metastatic nodal conglomerate, PRRT resulted in an impressive size reduction of over 75% after just 2 treatment cycles, indicating its potential effectiveness for aggressive neuroendocrine cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Striking Size Reduction of Rapidly Growing Pancreatic Neuroendocrine Carcinoma Metastatic Nodal Conglomerate After Only 2 Cycles of 177 Lu-DOTATATE. Somoza, EA., Duan, H., Shaheen, S., et al.[2022]

Citations

1.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.LBA588

[177Lu]Lu-DOTA-TATE in newly diagnosed patients with ...

Conclusion: 177Lu-DOTATATE significantly prolonged PFS and demonstrated a clinically meaningful ORR, compared with high-dose octreotide LAR, in ...

2.

jnm.snmjournals.org

jnm.snmjournals.org/content/jnumed/early/2024/03/21/jnumed.123.265703.full.pdf

Effectiveness and Safety of Retreatment with

The objective of the current study was to evaluate the real-world effectiveness and safety of retreatment with 177Lu-DOTATATE in patients with ...

3.

ncbi.nlm.nih.gov

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

Neuroendocrine Tumor 177Lutetium-Dotatate Therapy - NCBI

Clinical trials, including the landmark NETTER-1 study, have demonstrated significant improvements in progression-free survival, quality of life ...

4.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa1607427

Phase 3 Trial of 177 Lu-Dotatate for Midgut ...

Treatment with 177Lu-Dotatate resulted in markedly longer progression-free survival and a significantly higher response rate than high-dose ...

5.

frontiersin.org

frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.993182/full

Efficacy and safety of 177 Lu-DOTATATE targeted therapy ...

177 Lu-DOTATATE is effective and safe for advanced/metastatic pNETs, which can delay the progression of the disease, may improve patients' survival,

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12316713/

Safety and efficacy of re-treatment with [177Lu]Lu-DOTA ...

The aim of this study is to evaluate the effectiveness and safety of R-PRRT in patients with progressive metastatic GEP NET after a period of ...

7.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.e16198

177 Lu-DOTATATE peptide receptor radionuclide therapy ...

One patient had grade 3 renal toxicity secondary to treatment. 26 patients received retreatment with 177Lu-DOTATATE at progression with median ...

8.

jnm.snmjournals.org

jnm.snmjournals.org/content/58/supplement_1/242

initial dosimetry and safety results of the P-PRRT trial | Journal ...

Personalized 177Lu-octreotate peptide receptor radionuclide therapy of neuroendocrine tumors: initial dosimetry and safety results of the P-PRRT ...

9.

acsjournals.onlinelibrary.wiley.com

acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.34191

Long‐term survival and toxicity in patients with ...

Lutetium-177-octreotate peptide receptor radionuclide therapy is a safe and efficacious treatment for advanced neuroendocrine tumors.