Radioactive Agent for Cancer

(NeoRay Trial)

Recruiting in Palo Alto (17 mi)

+10 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Waitlist Available

Sponsor: Advanced Accelerator Applications

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests a new radioactive treatment for adults with advanced cancers that have a specific marker. The treatment aims to see if it is safe and effective by targeting and killing cancer cells using radiation.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are currently receiving NEP inhibitors or have taken certain investigational drugs within 30 days prior to the trial. Additionally, there are restrictions on prior systemic anti-cancer treatments and radiopharmaceuticals. It's best to discuss your specific medications with the trial team.

What data supports the idea that Radioactive Agent for Cancer is an effective treatment?

The available research shows that Radioactive Agent for Cancer, specifically [177Lu]Lu-PSMA-617, has shown impressive clinical and biochemical responses with low toxicity in treating prostate cancer. It has been used successfully in patients with advanced prostate cancer, particularly those who have not responded to other treatments. Additionally, combining this treatment with other therapies like external beam radiation therapy has shown potential to improve outcomes for patients with prostate cancer. This suggests that the treatment can be effective in controlling cancer and improving patient survival. ^{1 2 3 4 5}

What safety data exists for the radioactive cancer treatment [177Lu]-NeoB?

The provided research does not specifically mention safety data for [177Lu]-NeoB or its variants. However, it discusses the safety and therapeutic optimization of Lutetium-177 based radiopharmaceuticals, such as [177Lu]Lu-DOTATATE and [177Lu]Lu-PSMA-617, which are used in similar therapeutic contexts. These studies highlight the safety profile and management of adverse effects in Lutetium-177 based treatments, suggesting a focus on optimizing the risk-benefit trade-off in clinical settings. ^{4 6 7 8 9}

Is the treatment [177Lu]-NeoB a promising treatment for cancer?

[177Lu]-NeoB is a promising treatment for cancer because it uses a special radioactive element, Lutetium-177, which can target and destroy cancer cells. This approach has shown success in treating different types of cancer by delivering radiation directly to the tumor, potentially leading to better outcomes for patients. ^{1 4 10 11 12}

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

Adults with advanced solid tumors, especially breast, lung, prostate cancer, GIST or GBM. They must have a tumor that overexpresses GRPR and shows uptake of [68Ga]-NeoB on scans. Participants need at least one measurable lesion and no standard treatment options left. Specific criteria apply for different phases regarding prior treatments and renal function.

Inclusion Criteria

I have a metastatic tumor likely to overexpress GRPR and my kidney function is moderately impaired.

I have been diagnosed with GIST.

I am an adult with advanced or metastatic cancer.

Exclusion Criteria

I do not have any mental or physical health conditions that could affect the study.

I have had or currently have pancreatitis.

I am a woman able to have children and am not using strong birth control methods.

Treatment Details

Interventions

• [177Lu]-NeoB (Radiopharmaceutical)
• [68Ga]-NeoB (Radiopharmaceutical)

Trial Overview [177Lu]-NeoB is being tested to see how safe it is and how well it works in treating solid tumors with GRPR expression that absorb [68Ga]-NeoB. The trial will also look at how the body processes the drug and its effects on tumors through various imaging techniques.

Participant Groups

Group I: Phase IIa:Cohort E Experimental Treatment 3 Interventions

\[68 Ga\]-NeoB: 50 micrograms/dose at screening \[177Lu\]-NeoB: dose TBD based on Cohorts I-VI, 3 cycles q6w LCZ696: co-administered with \[177Lu\]-NeoB

Group II: Phase IIa: Cohort D Experimental Treatment 2 Interventions

\[68 Ga\]-NeoB: 50 micrograms/dose at screening \[177Lu\]-NeoB: dose TBD based on Cohorts I-VI, 3 cycles q6w

Group III: Phase IIa: Cohort C Experimental Treatment 2 Interventions

\[68 Ga\]-NeoB: 50 micrograms/dose at screening \[177Lu\]-NeoB: dose TBD based on Cohorts I-VI, 3 cycles q6w

Group IV: Phase IIa: Cohort B Experimental Treatment 2 Interventions

\[68 Ga\]-NeoB: 50 micrograms/dose at screening \[177Lu\]-NeoB: dose TBD based on Cohorts I-VI, 3 cycles q6w

Group V: Phase IIa: Cohort A Experimental Treatment 2 Interventions

\[68 Ga\]-NeoB: 50 micrograms/dose at screening \[177Lu\]-NeoB: dose TBD based on Cohorts I-VI, 3 cycles q6w

Group VI: Phase I: Cohort V Experimental Treatment 2 Interventions

\[68 Ga\]-NeoB: 50 micrograms/dose at screening \[177Lu\]-NeoB: 120% ECD for 3 cycles (q6w)

Group VII: Phase I: Cohort IV Experimental Treatment 2 Interventions

\[68 Ga\]-NeoB: 50 micrograms/dose at screening \[177Lu\]-NeoB: 100% ECD for 3 cycles (q6w)

Group VIII: Phase I: Cohort III Experimental Treatment 2 Interventions

\[68 Ga\]-NeoB: 50 micrograms/dose at screening \[177Lu\]-NeoB: 80% ECD for 3 cycles (q6w)

Group IX: Phase I: Cohort II Experimental Treatment 2 Interventions

\[68 Ga\]-NeoB: 50 micrograms/dose at screening \[177Lu\]-NeoB: 60% ECD for 3 cycles (q6w)

Group X: Phase I: Cohort I Experimental Treatment 2 Interventions

\[68 Ga\]-NeoB: 50 micrograms/dose at screening \[177Lu\]-NeoB: 50 mCi (1.85 GBq) cycle 1, 60% Estimated Cumulative Dose (ECD) for cycles 2-4, q6w

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

MD Anderson Cancer Center Houston, TX

Pittsburgh University Pittsburgh, PA

Stanford University Stanford, CA

John Hopkins University Baltimore, MD

More Trial Locations

Who Is Running the Clinical Trial?

Advanced Accelerator Applications

Lead Sponsor

Trials

37

Recruited

3,000+

Findings from Research

The novel radiopharmaceutical agent 177Lu-DOTA-DG was successfully synthesized with a high radiochemical yield and demonstrated excellent stability in human serum for up to 120 hours, indicating its potential for safe use in cancer imaging and therapy.

In preclinical studies, 177Lu-DOTA-DG caused significantly more DNA damage in cancer cells compared to untreated cells, suggesting its efficacy as a targeted treatment for cancer tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo and in vitro evaluation of 177Lu-labeled DOTA-2-deoxy-D-glucose in mice. A novel radiopharmaceutical agent for cells imaging and therapy. Zhang, J., Wang, Z., Liu, H., et al.[2019]

In a study of 52 patients undergoing Lu-177-PSMA-617 radioligand therapy for metastatic castration-resistant prostate cancer, the median overall survival was found to be 55.6 weeks, highlighting the treatment's potential efficacy.

Key predictors of overall survival included lower pre-therapeutic hemoglobin levels and higher lactate dehydrogenase (LDH) levels, as well as the presence of hepatic metastasis, indicating that these factors can help guide treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre- and intratherapeutic predictors of overall survival in patients with advanced metastasized castration-resistant prostate cancer receiving Lu-177-PSMA-617 radioligand therapy. Wrenger, R., Jüptner, M., Marx, M., et al.[2022]

The PROQURE-I study is investigating the safety and efficacy of combining standard external beam radiation therapy (EBRT) and androgen deprivation therapy (ADT) with a single dose of [177Lu]Lu-PSMA-617 in treating prostate cancer patients with locoregional lymph node disease (N1M0), aiming to improve outcomes for this challenging patient group.

This is the first prospective study to explore this combination in treatment-naïve men, with a focus on determining the maximum tolerated dose of [177Lu]Lu-PSMA-617 and assessing its tolerability and preliminary efficacy, suggesting a potential for enhanced anti-tumor effects with limited toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability of concurrent external beam radiotherapy and [177Lu]Lu-PSMA-617 for node-positive prostate cancer in treatment naïve patients, phase I study (PROQURE-I trial). van der Sar, ECA., Braat, AJAT., van der Voort-van Zyp, JRN., et al.[2023]

[177Lu]Lu-PSMA-617 is effective in targeting prostate cancer, but some patients do not respond well; ongoing research is exploring combination therapies to improve outcomes for both treatment-naïve and resistant patients.

Combining [177Lu]Lu-PSMA-617 with other treatments, such as alpha radiation emitters and immune checkpoint inhibitors, shows promise in enhancing therapeutic responses, particularly for patients who have developed resistance to initial therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Towards Improving the Efficacy of PSMA-Targeting Radionuclide Therapy for Late-Stage Prostate Cancer-Combination Strategies. Arbuznikova, D., Eder, M., Grosu, AL., et al.[2023]

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]

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]

177Lu is a promising radionuclide for therapy due to its favorable decay characteristics, achieving high yields of approximately 4 TBq/g from natural lutetium and 110 TBq/g from enriched lutetium after neutron bombardment.

The production process results in nearly 100% radionuclidic purity, making 177Lu a reliable option for therapeutic applications, with minimal impurities detected.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Production logistics of 177Lu for radionuclide therapy. Pillai, MR., Chakraborty, S., Das, T., et al.[2019]

The study successfully optimized the formulation of [177Lu]Lu-DOTA-Exendin-4, achieving over 95% radiolabeling yield, which is crucial for effective radiotherapy of insulinomas.

In vivo studies in mice demonstrated that [177Lu]Lu-DOTA-Exendin-4 specifically targets GLP-1 receptors, with significant accumulation in the pancreas and kidneys, indicating its potential efficacy and stability for therapeutic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preparation of [177Lu]Lu-DOTA-Ahx-Lys40-Exendin-4 for radiotherapy of insulinoma: a detailed insight into the radiochemical intricacies. Guleria, M., Das, T., Amirdhanayagam, J., et al.[2020]

References

1. Greece pubmed.ncbi.nlm.nih.gov

In vivo and in vitro evaluation of 177Lu-labeled DOTA-2-deoxy-D-glucose in mice. A novel radiopharmaceutical agent for cells imaging and therapy. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Pre- and intratherapeutic predictors of overall survival in patients with advanced metastasized castration-resistant prostate cancer receiving Lu-177-PSMA-617 radioligand therapy. [2022]

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

Tolerability of concurrent external beam radiotherapy and [177Lu]Lu-PSMA-617 for node-positive prostate cancer in treatment naïve patients, phase I study (PROQURE-I trial). [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and Therapeutic Optimization of Lutetium-177 Based Radiopharmaceuticals. [2023]

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

Towards Improving the Efficacy of PSMA-Targeting Radionuclide Therapy for Late-Stage Prostate Cancer-Combination Strategies. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

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

7. England pubmed.ncbi.nlm.nih.gov

Peptide receptor radionuclide therapy with 177Lu-DOTA-octreotate: dosimetry, nephrotoxicity, and the effect of hematological toxicity on survival. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Toxicity of trastuzumab labeled 177Lu on MCF7 and SKBr3 cell lines. [2015]

9. Italy pubmed.ncbi.nlm.nih.gov

Adverse events related to radium-223 treatment: "real-life" data from the Eudra-Vigilance database. [2021]

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

Monoclonal antibody-based therapy of a human tumor xenograft with a 177lutetium-labeled immunoconjugate. [2013]

11. England pubmed.ncbi.nlm.nih.gov

Production logistics of 177Lu for radionuclide therapy. [2019]

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

Preparation of [177Lu]Lu-DOTA-Ahx-Lys40-Exendin-4 for radiotherapy of insulinoma: a detailed insight into the radiochemical intricacies. [2020]