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

Trial Summary

What is the purpose of this trial?

There is no consensus in the literature on the best way to treat cystic lesions of the pituitary area. Patients who are symptomatic from these tumours are rare. The cystic form of tumours present special challenges since traditional treatment modalities (surgery and/or external radiation) are often not able to completely remove or treat the cyst wall without major morbidity or even mortality. There is no 'best practice' for the treatment of cystic tumours per se. Treatments available to patients with cystic sellar/parasellar tumours include conservative management using a 'wait and scan' approach, cyst drainage, and cyst removal via transsphenoidal and/or craniotomy approach (i.e. open surgery). Over the last 10 years we have treated approximately 8 patients with intracystic radiotherapy. All of these patients continue to be monitored clinically and radiologically and all have done well with stable regression of the cysts and no new neurological deficits. Over the past 2 years, 90yttrium colloid has been provided to CDHA through Health Canada's Special Access Program (SAP). It has only been of recent that Health Canada has requested a clinical trial to assess the benefit of intracystic radiotherapy over other available treatment options. The experimental treatment being proposed is the stereotactic intracavitary instillation of 90yttrium colloid for treatment of cystic lesions of the pituitary (sellar) and surrounding areas (parasellar).

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.

What data supports the effectiveness of the treatment 90Yttrium colloid for pituitary cancer?

Research on similar treatments, like Yttrium-90 citrate colloid used in joint therapy, shows that it effectively stays localized in the target area, which could suggest potential for targeting tumors. Additionally, studies on Yttrium-90 in other forms, such as microspheres for liver cancer, indicate its ability to deliver targeted radiation, which might be beneficial for treating pituitary cancer. ^{1 2 3 4 5}

Is 90Yttrium colloid safe for use in humans?

In a study involving 55 patients with prostate cancer, 90Yttrium colloid was used for pituitary ablation to relieve pain from bone metastases. The treatment was generally well-tolerated, with 80% of patients experiencing significant pain relief, suggesting a favorable safety profile in this context. ^{6 7 8 9 10}

How is the treatment 90Yttrium colloid unique for pituitary cancer?

The 90Yttrium colloid treatment is unique because it uses a radioactive substance, Yttrium-90, which can be precisely localized to target cancer cells, minimizing exposure to surrounding healthy tissues. This approach is different from traditional treatments as it offers a targeted form of radiation therapy, potentially reducing side effects and increasing effectiveness in treating pituitary cancer. ^{1 2 3 4 11}

Research Team

David Clarke

Principal Investigator

Capital District Health Auhtority

Eligibility Criteria

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.

My neurosurgeon thinks surgery is too risky for me.

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

Timeline

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

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]

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]

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]

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]

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]

References

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

Yttrium-90 citrate colloid for radioisotope synovectomy. [2004]

2. Germany pubmed.ncbi.nlm.nih.gov

[Biokinetics of tumor-affinity yttrium preparations--Part 1]. [2016]

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

Selective internal radiation therapy for nonresectable hepatocellular carcinoma with intraarterial infusion of 90yttrium microspheres. [2019]

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

Formulation and purification of therapeutic dose of 90Y-labeled peptides: Some interesting radiochemistry aspects. [2019]

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

Yttrium-90-EDTMP: a radiotherapeutic agent in the treatment of leukaemias. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Pituitary ablation in the relief of pain in advanced prostatic carcinoma. [2019]

7. China pubmed.ncbi.nlm.nih.gov

[Therapeutic efficacy of strontium-89-chloride for bone metastatic tumors without bone pain]. [2007]

8. Switzerland 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. [2020]

9. Japan pubmed.ncbi.nlm.nih.gov

Complete regression of multiple painful bone metastases from hepatocellular carcinoma after administration of strontium-89 chloride. [2016]

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

Adverse Events Associated With Radium-223 in Metastatic Prostate Cancer: Disproportionality Analysis of FDA Data Reflecting Worldwide Utilization. [2021]

11. United States 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. [2019]