I131-Omburtamab for Peritoneal Cancer

Overseen By Neeta Pandit-Taskar, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Disease progression, HIPEC, cardiac, 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: Unknown

Duration: 6-8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new treatment called 131I-omburtamab for peritoneal cancer. Researchers seek to determine if this drug can prevent cancer recurrence or slow its progression. The trial involves different groups: those with a specific cancer type called DSRCT (a rare tumor in the abdomen) and those with other tumors. Participants should have undergone surgery and have no active disease outside the abdomen or pelvis.

As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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, there are requirements for time to pass since prior chemotherapy and biologic therapy, so it's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that 131I-omburtamab may help treat certain cancers, such as neuroblastoma. In earlier studies, it was generally safe and caused only mild side effects. For instance, one study found that it did not expose healthy organs to significant radiation, making it safer to use alongside other treatments. Another study found that most patients did not experience serious side effects.

Although the FDA has not yet approved 131I-omburtamab for treating peritoneal cancer, its use in other conditions suggests it might be safe for many people. However, treatments can affect individuals differently. Patients should always discuss potential risks and benefits with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about 131 I-omburtamab for peritoneal cancer because it offers a targeted approach that differs from traditional treatments like chemotherapy. This treatment harnesses a radioactive isotope, I-131, linked to omburtamab, which specifically targets the B7H3 molecule found on certain cancer cells. By delivering radiation directly to the cancer cells, it aims to minimize damage to healthy tissue, potentially enhancing effectiveness and reducing side effects. This targeted mechanism is particularly promising for conditions like desmoplastic small round cell tumors (DSRCT), where standard treatments often fall short.

What evidence suggests that this trial's treatments could be effective for peritoneal cancer?

Research has shown that 131 I-omburtamab, a special antibody with a radioactive component, holds potential for treating certain cancers. Studies focused on neuroblastoma, particularly when it affects the brain and spinal cord, have found this treatment effective. Specifically, for patients with difficult-to-treat cancer spread in these areas, it resulted in an average survival of 58 months. Early research also found that 131 I-omburtamab was generally safe, causing few side effects and low radiation exposure to healthy organs. In this trial, participants will receive 131 I-omburtamab to explore its potential benefits for cancers in the abdominal area. Further research is needed to confirm its effectiveness in this context. ^{1 2 3 4 6}

Who Is on the Research Team?

Emily Slotkin, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for people with a rare cancer called Desmoplastic Small Round Cell Tumor (DSRCT) or other cancers in the lining of the abdomen. Participants must not have active liver disease or disease outside the abdomen, be over 1 year old, and able to follow safety rules during treatment. They should not have had certain treatments recently and must meet specific health criteria including organ function.

Inclusion Criteria

My DSRCT diagnosis with peritoneal involvement was confirmed at MSK.

I have my stem cells stored for treatment after 131 I-omburtamab.

Side effects from my previous treatments have mostly gone away.

Exclusion Criteria

I have not been treated with murine monoclonal antibodies or my HAMA level is below 1000U/ml.

I have a serious infection that antibiotics can't control.

My heart, lungs, and brain are mostly healthy; my kidneys, stomach, and liver are fairly healthy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 131I-omburtamab radioimmunotherapy and external beam radiotherapy

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• 131 I-omburtamab
• WA-IMRT
• WAP-IMRT

Trial Overview The study tests I131-Omburtamab's effects on preventing or delaying cancer return in DSRCT and peritoneal cancers. It's an investigational drug, meaning it isn't FDA-approved yet for these conditions. The trial also includes Whole Abdomen Intensity-Modulated Radiotherapy (WAP-IMRT), which is a precise radiation therapy technique.

How Is the Trial Designed?

Group I: Group C Experimental Treatment 1 Intervention

Participants with tumors other than DSRCT and will be enrolled onto an assessment arm to determine eligibility. Immunohistochemistry to assess B7H3 expression will be performed on frozen or paraffin embedded tissue using omburtamab (frozen tissue) or a commercially available anti-B7H3 antibody (if paraffin embedded).

Group II: Group B Experimental Treatment 1 Intervention

DSRCT patients who have macroscopic residual disease OR who have previously experienced progression of disease while on treatment but have subsequently had a GTR

Group III: Group A Experimental Treatment 2 Interventions

Participants with DSRCT who have undergone GTR of their abdominopelvic disease and who have no definitive radiological evidence of disease in liver or outside the abd/pelvis. Patients if deemed of likely benefit to the patient after completing IP RIT plus WAP-IMRT, or will be mandated if ANC is persistently \<500/ul despite use of G-CSF for \>1 week, or if patients experience life threatening febrile neutropenia.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Y-mAbs Therapeutics

Industry Sponsor

Trials

26

Recruited

1,600+

Y-mAbs Therapeutics, Inc

Collaborator

Trials

4

Recruited

490+

Published Research Related to This Trial

In a phase I trial involving 31 patients with desmoplastic small round cell tumor, the pharmacokinetics of intraperitoneally administered 124I-omburtamab showed a biphasic pattern, indicating a complex absorption and distribution process in the body.

The study demonstrated that PET/CT imaging can effectively assess the distribution of 124I-omburtamab in the peritoneal cavity and estimate radiation doses to both the peritoneal space and normal organs, which is crucial for optimizing future radioimmunotherapy treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biodistribution and Radiation Dosimetry of Intraperitoneally Administered 124I-Omburtamab in Patients with Desmoplastic Small Round Cell Tumors. Grkovski, M., Modak, S., Zanzonico, PB., et al.[2023]

Brief intraperitoneal radioimmunotherapy using (125)I-labeled monoclonal antibodies significantly increased median survival in mice with small-volume peritoneal carcinomatosis, from 32 days in control groups to up to 73 days with combined treatments.

The treatment demonstrated mild, transient hematologic toxicity with no weight loss, and a favorable tumor-to-healthy tissue uptake ratio, indicating its potential for safe use alongside other therapies after cytoreductive surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brief intraperitoneal radioimmunotherapy of small peritoneal carcinomatosis using high activities of noninternalizing 125I-labeled monoclonal antibodies. Boudousq, V., Ricaud, S., Garambois, V., et al.[2022]

Monoclonal antibody B72.3 coupled with 131I has shown a high localization rate of tumors, successfully identifying over 70% of tumors in patients with gastrointestinal, ovarian, and breast cancers during clinical trials.

Intraperitoneal administration of the MAb-radionuclide conjugate was particularly effective, detecting peritoneal lesions in 3 out of 10 patients that conventional methods missed, and localized peritoneal implants more than twice as effectively compared to intravenous administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Binding of radiolabeled MAb B72.3 administered intravenously and intraperitoneally in colorectal cancer patients. An overview. Schlom, J., Siler, K., Colcher, D., et al.[2016]

In a study of 36 ovarian cancer patients treated with intraperitoneal I-131 labeled monoclonal antibodies, higher doses (up to 158 mCi) led to significant marrow suppression, particularly in patients without prior exposure to the treatment (HAMA negative).

Among patients with assessable disease, treatment was more effective in those with smaller tumors, showing complete responses in 50% of patients with microscopic disease, while no responses were observed in patients with larger tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraperitoneal radioimmunotherapy for ovarian cancer: pharmacokinetics, toxicity, and efficacy of I-131 labeled monoclonal antibodies. Stewart, JS., Hird, V., Snook, D., et al.[2019]

In a study involving seven patients with small volume ovarian carcinoma, intraperitoneal monoclonal antibody guided radiotherapy did not show significant therapeutic benefits for solid tumors, as most patients experienced disease progression after treatment.

However, in a separate group of five patients with recurrent malignant ascites, the treatment successfully controlled ascites in three patients for an average of four months, indicating potential efficacy in managing this specific complication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The treatment of intraperitoneal malignant disease with monoclonal antibody guided 131I radiotherapy. Ward, B., Mather, S., Shepherd, J., et al.[2019]

In a study of 24 patients with persistent epithelial ovarian cancer, intraperitoneal treatment with 131I-labeled monoclonal antibodies showed potential effectiveness, especially in patients with small-volume disease (less than 2 cm), where four out of nine initial responders remained alive and disease-free for 6 months to 3 years.

Higher doses of 140 mCi or more of the radiolabeled antibodies were associated with better outcomes, suggesting that this dosage may enhance the therapeutic efficacy for patients with small-volume stage III ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibody-guided irradiation of advanced ovarian cancer with intraperitoneally administered radiolabeled monoclonal antibodies. Epenetos, AA., Munro, AJ., Stewart, S., et al.[2017]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33119478/

Results of a Phase I Study - PubMed - NIH IP RIT 131 I-omburtamab was well tolerated with minimal toxicities. Radiation exposure to normal organs was low, making combination therapy ...

2. openmedscience.com openmedscience.com/iodine-131-omburtamab-a-breakthrough-in-neuroblastoma-therapy/

Iodine-131 Omburtamab in Neuroblastoma 131 I-Omburtamab is a radiolabelled monoclonal antibody showing promising results in treating neuroblastoma, particularly in cases with central nervous system ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05063357

Study Details | NCT05063357 | 131I-omburtamab ... The aim of this trial is to determine the efficacy and safety of 131I-omburtamab in patients with DIPG that have not progressed following external beam ...

4. oncidiumfoundation.org oncidiumfoundation.org/molecules/i-131-omburtamab/

I-131-Omburtamab Results from a pivotal study of 131I-Omburtamab in Refractory Leptomeningeal Metastasis from Neuroblastoma showed a 58 months average survival for the patients ...

5. jnm.snmjournals.org jnm.snmjournals.org/content/64/6/946

Radioimmunoscintigraphy and Pretreatment Dosimetry of 131I ... The antibody omburtamab (previously 8H9) was radiolabeled with 131I by Memorial Sloan Kettering Cancer Center's Radiochemistry and Molecular ...

6. trial.medpath.com trial.medpath.com/clinical-trial/b18c99b2ff89dc45/nct01099644-phase-1-radioimmunotherapy-131i-8h9-tumors

Intraperitoneal RIT With 131I-8H9 for Pts With DSRCT and ... The purpose of this study is to test the safety of a new medicine called antibody 8H9 injected into the lining of the abdomen or peritoneum, where the tumor ...