90Yttrium Colloid for Pituitary Cancer

Overseen By Andrea LO Hebb, PhD, RN

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: David Clarke

Disqualifiers: Solid tumour, Pregnancy, Hypersensitivity, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 1 day

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for cystic pituitary tumors, which are rare and difficult to fully remove with surgery or traditional radiation. The treatment uses 90yttrium colloid, a type of radiotherapy placed directly into the tumor's cystic cavity, aiming to shrink the cysts without major side effects. People with cystic tumors near their pituitary gland, who have been advised they might need surgery, could be suitable candidates for this trial. The goal is to determine if this approach works better than other current treatments. As a Phase 3 trial, this treatment is in the final step before FDA approval, offering patients a chance to participate in a potentially groundbreaking therapy.

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 90yttrium colloid may help treat certain types of tumors. In earlier studies, patients who received this treatment for similar conditions experienced a significant reduction in tumor size. Specifically, one study reported a 74.7% decrease in cyst size after treatment, indicating that the treatment can effectively shrink cysts.

Regarding safety, 90yttrium colloid has been used in other medical treatments, such as for liver cancer, and is generally well-tolerated. While side effects can occur, they are usually manageable. Previous patients did not report any major new health issues after receiving the treatment, which is reassuring.

This treatment has already been administered to patients in Canada under special access programs. Its testing in a late-stage trial suggests confidence in its safety. However, as with any medical treatment, potential risks should be discussed with a doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for pituitary cancer, which often involve surgery and radiation therapy, 90Yttrium colloid offers a cutting-edge approach by being inserted directly into the cystic cavity of the tumor. Researchers are excited about this treatment because it involves a novel delivery method that allows the radioactive 90Yttrium to target the tumor precisely, potentially minimizing damage to surrounding healthy tissues. This localized approach might offer a more effective and less invasive treatment option, leading to better outcomes and fewer side effects for patients.

What evidence suggests that 90yttrium colloid is effective for pituitary cancer?

Research has shown that 90yttrium colloid, the treatment under study in this trial, can significantly shrink cystic tumors. In one study, patients experienced an average reduction of 74.7% in cyst size after treatment. Another study found that 82% of these cases maintained this size reduction for five years. This treatment has shown promise in managing cysts by reducing their size while preserving vision and hormone functions. These findings suggest that 90yttrium colloid could be a viable option for treating cysts in the pituitary area when other treatments might not be effective. ^{1 4 5 6 7}

Who Is on the Research Team?

David Clarke

Principal Investigator

Capital District Health Auhtority

Are You a Good Fit for This Trial?

This trial is for adults over 17 with cystic tumors in the pituitary region, confirmed by tests or imaging. Candidates must need surgery as per a neurosurgeon's assessment, be managed at the Halifax Neuropituitary Program surgical clinic, and agree to both surgery and study participation. Pregnant or breastfeeding individuals, those allergic to 90yttrium colloid, at high surgical risk, or with solid tumors cannot join.

Inclusion Criteria

Tumour measurements and/or tumour volume can be calculated

My neurosurgeon has decided I need surgery.

I am 17 years old or older.

Exclusion Criteria

I am not allergic to the drug 90yttrium colloid.

Pregnant or breast feeding at time of surgical consent and/or surgery

My neurosurgeon thinks surgery is too risky for me.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Stereotactic intracavitary instillation of 90yttrium colloid into the cystic cavity

1 day

1 visit (in-person)

Follow-up

Participants are monitored for cyst shrinkage and resolution of clinical symptoms

12 months

Regular visits (in-person) and MRI assessments

Secondary Evaluation

Localization of intracystic 90yttrium colloid by PET-CT

Within 3 weeks of treatment

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• 90yttrium colloid

Trial Overview

The trial is testing an experimental treatment where a radioactive substance called 90yttrium colloid is placed directly into the cystic lesions of the pituitary area using stereotactic techniques. This approach aims to treat these challenging tumors without major risks associated with traditional surgeries or external radiation.

How Is the Trial Designed?

Group I: 90yttrium colloid Experimental Treatment 1 Intervention

90 Yttrium colloid will be inserted into the cystic cavity. Based on clinical expertise, the treating neurosurgeon will determine the appropriate surgical procedure for each patient on an individual basis which will be reflected in the surgical consent the patient is presented and signs.

90yttrium colloid is already approved in European Union, Canada for the following indications:

Approved in European Union as Yttrium-90 citrate for:

• Hypertrophy of the synovial membrane of the knee joints
• Rheumatoid arthritis
• Osteoarthritis
• Spondyloarthropathy
• Villonodular synovitis

Approved in Canada as Yttrium-90 citrate for:

• Cystic sellar/parasellar tumors

Who Is Running the Clinical Trial?

David Clarke

Lead Sponsor

Trials

2

Recruited

40+

Published Research Related to This Trial

Yttrium-90 chelated with EDTMP shows high uptake in bone and quick clearance from soft tissues, making it a promising option for targeted treatment.

The biological half-life of Yttrium-90 in bone exceeds 72 hours, and its effective dose can be halved through safe chelation therapy with calcium DTPA, potentially reducing side effects in leukemia treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Yttrium-90-EDTMP: a radiotherapeutic agent in the treatment of leukaemias. Keeling, AA., Vaughan, AT., Beaney, RP.[2019]

In a study of 71 patients with nonresectable hepatocellular carcinoma (HCC), treatment with intraarterial 90Y microspheres resulted in an 89% objective response rate based on tumor marker levels, with 26.7% of patients showing a significant reduction in tumor volume after the first treatment.

The treatment was well tolerated, with no significant side effects like bone-marrow toxicity or radiation hepatitis, and it demonstrated the potential to convert nonresectable tumors into resectable ones, highlighting its efficacy and safety in managing HCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective internal radiation therapy for nonresectable hepatocellular carcinoma with intraarterial infusion of 90yttrium microspheres. Lau, WY., Ho, S., Leung, TW., et al.[2019]

The yttrium-90 citrate colloid effectively targets the synovial membrane in joints, minimizing radiation exposure to surrounding tissues, which enhances safety during treatment.

In a study involving 28 patients, the formulation demonstrated excellent localization, with all of the injected yttrium-90 remaining in the joint area, indicating its potential efficacy for targeted therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Yttrium-90 citrate colloid for radioisotope synovectomy. Bowen, BM., Darracott, J., Garnett, ES., et al.[2004]

Strontium-89-chloride demonstrated a 74% response rate in treating nonpainful bone metastases in a study of 54 patients, indicating its efficacy in this patient population.

The treatment was generally safe, with side effects like mild and reversible thrombocytopenia and neutropenia, and showed a significantly lower response rate in patients with larger metastases (focal size >2 cm).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapeutic efficacy of strontium-89-chloride for bone metastatic tumors without bone pain]. Ouyang, W., Liu, JH., Liu, WY.[2007]

A 69-year-old man with painful bone metastases from liver cancer experienced complete pain relief 3 months after receiving an intravenous injection of strontium-89 chloride, without the need for opioids.

Four months post-treatment, the patient's multiple bone metastases showed complete regression, and he lived for an additional year without any recurrence of bone metastasis, highlighting the potential efficacy of strontium-89 in treating bone pain and metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complete regression of multiple painful bone metastases from hepatocellular carcinoma after administration of strontium-89 chloride. Suzawa, N., Yamakado, K., Takaki, H., et al.[2016]

The use of 87Y-NTA-EDTMP-Ca resulted in similar tumor accumulation of the radionuclide compared to 87Y-citrate, but with significantly lower radioactivity in surrounding organs like the liver and spleen, leading to better tumor-to-background ratios.

Melanomas showed 2-3 times higher radioactivity accumulation than mammary carcinomas after treatment with 87Y-NTA-EDTMP-Ca, and intratumoral application achieved comparable radioactivity levels to intraperitoneal application within just 4 hours, suggesting a more effective targeting for tumor therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Biokinetics of tumor-affinity yttrium preparations--Part 1]. Schomäker, K., Hientzsch, B., Franke, WG., et al.[2016]

A new protocol has been developed to effectively remove harmful 90Sr impurities from Yttrium-90, ensuring that the therapeutic dose of 90Y-DOTA-TATE is safe for human use, with a radiochemical purity exceeding 98%.

The optimized 90Y-DOTA-TATE was successfully used in preliminary clinical investigations for patients with neuroendocrine tumors, indicating its potential for broader clinical application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Formulation and purification of therapeutic dose of 90Y-labeled peptides: Some interesting radiochemistry aspects. Chakravarty, R., Chakraborty, S., Dash, A.[2019]

The newly synthesized Bz-DTPA-oct analogue showed a significantly slower loss of yttrium-90 in serum compared to the DTPA-octreotide, indicating better stability for potential therapeutic use.

In vivo studies demonstrated that [90Y]-Bz-DTPA-oct rapidly accumulates in somatostatin receptor-positive tumors, achieving high tumor-to-nontumor ratios, which suggests its efficacy for targeted radiotherapy in treating these types of tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and characterisation of [90Y]-Bz-DTPA-oct: a yttrium-90-labelled octreotide analogue for radiotherapy of somatostatin receptor-positive tumours. Smith-Jones, PM., Stolz, B., Albert, R., et al.[2019]

In a study of 55 patients with bone metastases from prostate cancer, pituitary ablation using Yttrium 90 resulted in significant pain relief for 80% of patients, with 12 patients becoming completely pain-free.

Post-treatment, the need for narcotics decreased from 39 patients requiring them before the procedure to only 12 afterwards, highlighting the efficacy of pituitary ablation in managing pain, although it did not improve survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pituitary ablation in the relief of pain in advanced prostatic carcinoma. Fitzpatrick, JM., Gardiner, RA., Williams, JP., et al.[2019]

Radium-223 dichloride (Xofigo®) has shown significant survival benefits for prostate cancer patients with bone metastases and a generally favorable safety profile, but its combination with abiraterone and prednisone may increase risks of death and fractures.

A retrospective analysis of approximately 1500 prostate cancer patients revealed that radium-223 can lead to hematological-related side effects, and its safety profile may vary when used with other treatments, highlighting the need for further studies to clarify its toxicological effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective Toxicological Profiling of Radium-223 Dichloride for the Treatment of Bone Metastases in Prostate Cancer Using Adverse Event Data. Soldatos, TG., Iakovou, I., Sachpekidis, C.[2020]

Radium-223, used for treating metastatic castrate-resistant prostate cancer, shows significant adverse events (AEs) such as health deterioration, bone pain, and hematologic issues, including anemia and thrombocytopenia, based on an analysis of 2182 cases from the FAERS database.

Patients are receiving only about half the necessary dose of radium-223 to achieve survival benefits, indicating a potential gap in treatment efficacy and highlighting the need for careful monitoring of its real-world use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events Associated With Radium-223 in Metastatic Prostate Cancer: Disproportionality Analysis of FDA Data Reflecting Worldwide Utilization. Huynh-Le, MP., Shults, RC., Connor, MJ., et al.[2021]

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