Radio-labeled Antibody for Colorectal Cancer

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Cardiac disease, CNS tumor, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: 1 day

30 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine whether our drug, 124I-huA33, can safely detect colorectal cancer.

Do I have to stop taking my current medications for the trial?

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 Iodine-124 labeled humanized A33 for colorectal cancer?

Research shows that the monoclonal antibody A33, when labeled with radioactive iodine, effectively targets and binds to colorectal cancer cells, which may help in treating the cancer. Studies with similar iodine-labeled antibodies have demonstrated good tumor-targeting abilities, suggesting potential effectiveness for this treatment. ^{1 2 3 4 5}

Is the radio-labeled antibody A33 generally safe for humans?

Studies on the radio-labeled antibody A33, used in colon cancer patients, show that it has been tested for safety, with attention to how it clears from the body. The humanized form of the antibody clears more slowly than the murine (mouse-derived) form, requiring longer-term safety precautions, but no specific safety issues were highlighted. ^{1 2 3 4 5}

How does the radio-labeled antibody treatment for colorectal cancer differ from other treatments?

This treatment uses a radio-labeled antibody, which is a special protein that targets cancer cells and delivers radiation directly to them, potentially reducing damage to healthy cells. This approach is different from traditional chemotherapy, which affects both cancerous and healthy cells, and it offers a more targeted way to treat colorectal cancer. ^{1 2 3 5 6}

Research Team

Neeta Pandit-Taskar, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults with confirmed colorectal cancer who are fit enough for surgery/biopsy and have adequate organ function. They must not be pregnant, breastfeeding, or have heart disease, active brain tumors, or prior A33 treatment.

Inclusion Criteria

The following laboratory results within the last 2 weeks prior to study day 1: Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L, Platelet count ≥ 75 x 10^9/L, Serum bilirubin ≤ 2.5 mg/dL, Serum creatinine ≤ 2.0 mg/dL, White Blood Count (WBC) ≥ 3,000/mm^3, Age ≥ 18 years. Children of all ages are not included as colon cancer is extremely rare in children

My colorectal cancer was confirmed at MSKCC.

I am eligible for surgery or biopsy for my colorectal cancer.

Exclusion Criteria

I do not have severe heart disease.

I have been treated with A33 or tested positive for huA33 HAHA.

Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single IV or IA infusion of 4mCi-10mCi/10mg 124I-huA33, followed by PET scans and optional IVIG administration

1 day

1 visit (in-person)

Imaging and Surgery/Biopsy

PET scans are conducted, and surgery or biopsy is scheduled 8-10 days after treatment to assess tumor uptake

8-10 days

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including blood samples for immunogenicity

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• Iodine-124 labeled humanized A33

Trial Overview The study tests if a drug called 124I-huA33 can safely identify colorectal cancer in patients. It involves using a radioactive antibody to detect the presence of cancer cells.

Participant Groups

Group I: Radio-labeled huA33 Antibody Experimental Treatment 1 Intervention

Patients will receive a single I-V infusion of 4mCi-10mCi/10mg 124I-huA33 in 5-30 mL of 5% human serum albumin (HAS) in normal saline, over 5 minutes-4 hours. Patients will be studied with 124I-huA33 positron-emission tomography (PET) and ex-vivo quantitation of tumor uptake . Blood samples will be obtained for pharmacokinetic analysis at 5, 15, 60, and 120 minutes after completion of IV, on and before or after PET scanning on subsequent days. Surgery (or biopsy) will be scheduled to occur 8- 10 days after administration of 124I-huA33. The 8-10 day imaging session will be scheduled for the morning of surgery or biopsy, approximately 1-6 hours before the procedure.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Ludwig Institute for Cancer Research

Collaborator

Trials

62

Recruited

1,700+

Findings from Research

The combination of the anti-EGFR monoclonal antibody C225 with 125-iodine radiation significantly enhances the inhibition of colorectal cancer cell growth compared to either treatment alone, with a sensitizer enhancement ratio of approximately 1.4.

C225 increases radiation-induced apoptosis and impairs DNA repair mechanisms, as evidenced by lower levels of DNA repair proteins and reduced Akt signaling, suggesting a mechanism for its radiosensitizing effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined effects of C225 and 125-iodine seed radiation on colorectal cancer cells. Liu, J., Wang, H., Qu, A., et al.[2021]

References

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

Combined effects of C225 and 125-iodine seed radiation on colorectal cancer cells. [2021]

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

Relative therapeutic efficacy of (125)I- and (131)I-labeled monoclonal antibody A33 in a human colon cancer xenograft. [2007]

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

Compartmental analysis of the pharmacokinetics of radioiodinated monoclonal antibody B72.3 in colon cancer patients. [2019]

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

Radiotheranostic Targeting Cancer Stem Cells in Human Colorectal Cancer Xenografts. [2021]

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

Clearance kinetics and external dosimetry of 131I-labeled murine and humanized monoclonal antibody A33 in patients with colon cancer: radiation safety implications. [2021]

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

Radioimmunodetection of colorectal cancer metastases with 131I-labeled monoclonal antibody B72.3: a pilot study to determine efficacy of detection and pharmacokinetics. [2019]