Personalized PRRT for Neuroendocrine Tumors

(P-PRRT Trial)

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

275 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

In this study, peptide receptor radionuclide therapy (PRRT) with 177Lu-Octreotate (LuTate) will be personalized, i.e. administered activity of LuTate will be tailored for each patient to maximize absorbed radiation dose to tumor, while limiting that to healthy organs. The purpose of this study is to: * Assess the objective (radiological), symptomatic and biochemical response rates following an induction course of personalized PRRT; * Assess the overall, the disease-specific, and the progression-free survival following P-PRRT; * Correlate therapeutic response and survival with tumor absorbed radiation dose; * Evaluate the acute, subacute and chronic adverse events following P-PRRT; * Correlate toxicity (i.e. occurence and severity of adverse events) with absorbed radiation doses to organs at risk; * Optimize the quantitative SPECT imaging-based dosimetry methods in a subset of 20 patients (sub-study funded by the Canadian Institutes of Health Research). This study also has a compassionate purpose, which is to provide access to PRRT to patients.

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 177Lu-Octreotate safe for humans?

177Lu-Octreotate, used in peptide receptor radionuclide therapy (PRRT), has been shown to be generally safe for treating neuroendocrine tumors, with studies reporting favorable safety profiles in patients with various types of these tumors. ^{1 2 3 4 5}

What makes the treatment 177Lu-Octreotate unique for neuroendocrine tumors?

177Lu-Octreotate is a type of peptide receptor radionuclide therapy (PRRT) that targets somatostatin receptors on neuroendocrine tumors, delivering radiation directly to the cancer cells. This treatment is unique because it can improve progression-free survival and quality of life, and it has shown significant efficacy in reducing tumor size in patients with advanced neuroendocrine tumors. ^{1 2 6 7 8}

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

Research shows that 177Lu-Octreotate, a type of peptide receptor radionuclide therapy (PRRT), can improve quality of life and slow disease progression in patients with neuroendocrine tumors. It has also been effective in reducing the size of metastatic tumors and providing symptom relief in similar conditions. ^{2 6 7 9 10}

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 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 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]

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]

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]

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]

Citations

1. Switzerland pubmed.ncbi.nlm.nih.gov

Treatment with the radiolabelled somatostatin analog Lu-DOTATATE for advanced pancreatic neuroendocrine tumors. [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. United States 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. [2022]

4. England pubmed.ncbi.nlm.nih.gov

The efficacy, toxicity and survival of salvage retreatment PRRT with 177Lu-DOTATATE in patients with progressive NET following initial course of PRRT. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Retreatment with peptide receptor radionuclide therapy in patients with progressing neuroendocrine tumours: efficacy and prognostic factors for response. [2022]

6. Japan pubmed.ncbi.nlm.nih.gov

Safety and efficacy of peptide receptor radionuclide therapy with 177Lu-DOTA0-Tyr3-octreotate in combination with amino acid solution infusion in Japanese patients with somatostatin receptor-positive, progressive neuroendocrine tumors. [2022]

7. 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]

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

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

9. Germany pubmed.ncbi.nlm.nih.gov

177 Lu-Dota-octreotate radionuclide therapy of advanced gastrointestinal neuroendocrine tumors: results from a phase II study. [2022]

10. Australia 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. [2022]