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

31 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to test any good and bad effects of the study drug 131I-omburtamab. 131I-omburtamab could prevent the cancer from returning, or delay the cancer from getting worse, but it could also cause side effects. Researchers hope to learn more about how 131I-omburtamab works in the body, and how effective it is in treating cancer. 131I-Omburtamab is not approved by the FDA to treat DSRCT or other cancers of the peritoneum.

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.

What data supports the effectiveness of the drug I131-Omburtamab for peritoneal cancer?

Research on similar treatments, like intraperitoneal radioimmunotherapy with I-131 labeled monoclonal antibodies, shows potential effectiveness in treating small-volume ovarian cancer, with some patients experiencing complete responses. This suggests that I131-Omburtamab might also be effective for small-volume peritoneal cancer. ^{1 2 3 4 5}

What makes the drug I131-Omburtamab unique for treating peritoneal cancer?

I131-Omburtamab is unique because it is administered directly into the peritoneal cavity (the space in the abdomen that contains the intestines, stomach, and liver), allowing it to target cancer cells more directly and potentially reduce systemic side effects. This approach is different from traditional treatments that are often given intravenously and may not localize as effectively to the peritoneal area. ^{1 2 4 5 6}

Research Team

Emily Slotkin, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

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

Intraperitoneal radioimmunotherapy for ovarian cancer: pharmacokinetics, toxicity, and efficacy of I-131 labeled monoclonal antibodies. [2019]

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

The treatment of intraperitoneal malignant disease with monoclonal antibody guided 131I radiotherapy. [2019]

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

Antibody-guided irradiation of advanced ovarian cancer with intraperitoneally administered radiolabeled monoclonal antibodies. [2017]

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

Biodistribution and Radiation Dosimetry of Intraperitoneally Administered 124I-Omburtamab in Patients with Desmoplastic Small Round Cell Tumors. [2023]

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

Brief intraperitoneal radioimmunotherapy of small peritoneal carcinomatosis using high activities of noninternalizing 125I-labeled monoclonal antibodies. [2022]

6. Sweden pubmed.ncbi.nlm.nih.gov

Binding of radiolabeled MAb B72.3 administered intravenously and intraperitoneally in colorectal cancer patients. An overview. [2016]