Radspherin for Ovarian Cancer

Recruiting at 5 trial locations

Overseen By Trine Jensen Gjertsen

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Oncoinvent AS

Must be taking: NACT

Must not be taking: Bevacizumab

Disqualifiers: BRCA mutations, CNS metastasis, 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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6-8 weeks

114 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot take any other cancer therapy within 4 weeks before and after the surgery, and you must not have taken bevacizumab within 5 weeks prior to the surgery.

What data supports the effectiveness of the treatment Radspherin for ovarian cancer?

Research shows that Radspherin, which uses radium-224 attached to calcium carbonate microparticles, can effectively target and treat small cancer spread in the abdominal area. In mice studies, it improved survival rates when used alone or combined with chemotherapy, suggesting it could be a promising treatment for ovarian cancer. ^{1 2 3 4 5}

Is Radspherin safe for use in humans?

Studies in mice suggest that Radspherin, which uses radium-224, mainly stays in the targeted area and has reduced bone uptake, indicating a promising safety profile for localized treatment. However, human safety data is still being evaluated in ongoing clinical trials. ^{1 2 3 4 5}

How is the treatment Radspherin unique for ovarian cancer?

Radspherin is unique because it uses radium-224, a radioactive element, attached to calcium carbonate microparticles to deliver targeted radiation directly to the peritoneal cavity, where ovarian cancer often spreads. This approach allows for localized treatment of cancer cells with minimal impact on surrounding healthy tissues, differing from traditional chemotherapy that affects the whole body. ^{1 2 3 4 6}

What is the purpose of this trial?

This is a Phase 2, controlled, randomised, parallel assignment, open label, multicentre study to evaluate efficacy and safety of a single intraperitoneal injection of Radspherin® in patients with primary advanced high-grade serous or high-grade endometrioid epithelial ovarian cancer, fallopian tube, or primary peritoneal cancer, with peritoneal metastasis that are HR proficient and scheduled to undergo NACT and IDS. The study will be conducted in 2 parts; first, a Safety Lead-in Cohort will be recruited followed by the randomised part of the study. For both parts of the study, patients must be scheduled to undergo NACT and IDS and complete resection to no residual tumour (R0) should be deemed to be achievable during diagnostic work-up. Patients in both parts of the study will undergo the same procedures and assessments.

Eligibility Criteria

This trial is for patients with advanced ovarian, fallopian tube, or primary peritoneal cancer that has spread to the lining of the abdomen and are able to undergo chemotherapy and surgery. Participants must have a specific type of tumor (high-grade serous or endometrioid) that repairs DNA normally (HR proficient).

Inclusion Criteria

Able and willing to provide written informed consent and to comply with the clinical study protocol (CSP)

I am a woman aged 18 or older.

I agree to use effective birth control if I can have children and am treated with Radspherin®.

Exclusion Criteria

My cancer got worse during the first 3-4 rounds of chemotherapy.

I have had radiotherapy to my abdomen or pelvis before.

I do not have active liver disease or a positive test for hepatitis B, C, or HIV.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-in

A Safety Lead-in Cohort will be recruited to evaluate the safety of the treatment

4-6 weeks

Treatment

Participants receive a single intraperitoneal injection of Radspherin® and undergo NACT and IDS

6-8 weeks

Follow-up

Participants are monitored for progression-free survival and peritoneal progression-free survival

24 months

Treatment Details

Interventions

• Radspherin

Trial Overview The study tests Radspherin®, given as a single injection into the abdomen, in two parts: first assessing safety in a small group, then randomly assigning participants to receive Radspherin® or not alongside standard treatment. All patients will have chemotherapy and surgery aimed at removing all visible tumor.

Participant Groups

Group I: Radspherin Experimental Treatment 1 Intervention

Group II: Control Active Control 1 Intervention

Radspherin is already approved in United States for the following indications:

Approved in United States as Radspherin for:

• Peritoneal metastases from ovarian cancer (Fast Track Designation)

Who Is Running the Clinical Trial?

Oncoinvent AS

Lead Sponsor

Trials

3

Recruited

230+

Findings from Research

Calcium carbonate microparticles can effectively carry radium-224 for targeted internal therapy in treating micrometastatic cancers, particularly in the peritoneal cavity, showing over 95% retention of radioactivity for up to a week in vitro.

The study demonstrated that the distribution of radium-224 in the body is influenced by the amount of microparticles administered, suggesting that these microparticles can minimize unwanted skeletal uptake while delivering localized treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ra-224 labeling of calcium carbonate microparticles for internal α-therapy: Preparation, stability, and biodistribution in mice. Westrøm, S., Malenge, M., Jorstad, IS., et al.[2021]

The study of six colorectal cancer patients receiving radium-224 adsorbed to calcium carbonate micro particles (224Ra-CaCO3-MP) showed a median effective whole-body half-life of approximately 3 days, indicating a manageable duration of radiation exposure post-treatment.

Hospital workers can safely care for 200-400 patients treated with 224Ra-CaCO3-MP annually without exceeding the effective dose limit of 6 mSv, while family members and the public are expected to receive minimal exposure (below 0.25 mSv), suggesting no need for additional safety restrictions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation safety considerations for the use of radium-224-calciumcarbonate-microparticles in patients with peritoneal metastasis. Grønningsæter, SR., Blakkisrud, J., Selboe, S., et al.[2023]

Radium-224-labeled CaCO3 microparticles have shown significant antitumor effects in treating advanced-stage ovarian cancer in a mouse model, demonstrating improved survival rates with lower doses compared to cationic 224Ra in solution.

The most effective treatment was achieved with microparticles at higher specific activities (2.6 and 4.6 kBq/mg), indicating that optimizing the ratio of activity to mass can enhance therapeutic outcomes in targeting peritoneal metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Calcium Carbonate Microparticles as Carriers of 224Ra: Impact of Specific Activity in Mice with Intraperitoneal Ovarian Cancer. Li, RG., Napoli, E., Jorstad, IS., et al.[2021]

The novel treatment using 224Ra-labeled calcium carbonate microparticles (224Ra-CaCO3-MP) showed a slight therapeutic benefit in extending survival in a mouse model of ovarian cancer, with median survival ratios ranging from 1.1 to 1.3 compared to control.

When combined with standard chemotherapy regimens like carboplatin-paclitaxel or carboplatin-pegylated liposomal doxorubicin, 224Ra-CaCO3-MP demonstrated a synergistic effect on overall survival, indicating its potential as an effective treatment option for micrometastatic peritoneal disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraperitoneal alpha therapy with 224Ra-labeled microparticles combined with chemotherapy in an ovarian cancer mouse model. Wouters, R., Westrøm, S., Berckmans, Y., et al.[2022]

Radium-224 (224Ra) labeled calcium carbonate (CaCO3) microparticles show promise as a localized cancer therapy, particularly for micrometastatic disease, by effectively delivering alpha-particle radiation.

The study found that 220Rn diffusion is reduced in these microparticles compared to cationic solutions, and over 70% of the longer-lived lead-212 (212Pb) can be re-adsorbed onto the microparticles, potentially enhancing therapeutic efficacy in the peritoneal cavity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radon-220 diffusion from 224Ra-labeled calcium carbonate microparticles: Some implications for radiotherapeutic use. Napoli, E., Bønsdorff, TB., Jorstad, IS., et al.[2021]

Radspherin®, a novel treatment using radium-224, was well tolerated in a phase 1 study with 23 patients, showing no dose-limiting toxicities and no serious adverse events directly related to the treatment.

The study demonstrated that Radspherin® effectively distributes evenly in the peritoneal cavity, suggesting its potential to target residual cancer cells after surgery and chemotherapy for colorectal cancer with peritoneal metastasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First experience with 224Radium-labeled microparticles (Radspherin®) after CRS-HIPEC for peritoneal metastasis in colorectal cancer (a phase 1 study). Larsen, SG., Graf, W., Mariathasan, AB., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Ra-224 labeling of calcium carbonate microparticles for internal α-therapy: Preparation, stability, and biodistribution in mice. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Radiation safety considerations for the use of radium-224-calciumcarbonate-microparticles in patients with peritoneal metastasis. [2023]

3. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Calcium Carbonate Microparticles as Carriers of 224Ra: Impact of Specific Activity in Mice with Intraperitoneal Ovarian Cancer. [2021]

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

Intraperitoneal alpha therapy with 224Ra-labeled microparticles combined with chemotherapy in an ovarian cancer mouse model. [2022]

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

Radon-220 diffusion from 224Ra-labeled calcium carbonate microparticles: Some implications for radiotherapeutic use. [2021]

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

First experience with 224Radium-labeled microparticles (Radspherin®) after CRS-HIPEC for peritoneal metastasis in colorectal cancer (a phase 1 study). [2023]