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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if 124I-huA33, a radio-labeled antibody, can safely and accurately detect colorectal cancer. Participants receive a single infusion of the drug, followed by imaging to assess its ability to locate cancer cells. Individuals with confirmed colorectal cancer who are planning surgery or a biopsy may qualify. The trial seeks participants expected to live at least three more months and who can manage daily activities independently. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research in cancer detection.

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 prior data suggests that this radio-labeled antibody is safe for detecting colorectal cancer?

Research has shown that 124I-huA33, a special type of antibody with a small amount of radiation, has been tested for safety in detecting colorectal cancer. In earlier studies, patients received a single dose of 124I-huA33, and researchers monitored them closely. These studies examined how the drug moves through the body and its effectiveness in identifying cancer cells.

The results indicated that 124I-huA33 was generally safe for patients. Some experienced mild side effects, but these were not serious. The research aimed to ensure the treatment does not cause major harm while helping doctors clearly identify cancerous areas using PET scans, a type of imaging test.

Overall, these studies suggest that 124I-huA33 is a safe method for detecting colorectal cancer, with careful monitoring to manage any mild side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for colorectal cancer, which often involve chemotherapy and radiation, the Iodine-124 labeled humanized A33 (124I-huA33) antibody is unique because it uses a radio-labeled antibody to specifically target cancer cells. This innovative approach allows for precise delivery of radiation directly to the tumor, reducing damage to healthy tissues. Researchers are excited about this treatment because it combines imaging and therapy, enabling them to visualize and quantify tumor uptake with positron-emission tomography (PET) while simultaneously treating the cancer. This dual capability could lead to more accurate treatment assessments and potentially more effective outcomes for patients.

What evidence suggests that this radio-labeled antibody is effective for detecting colorectal cancer?

Research has shown that a special antibody called 124I-huA33, which participants in this trial will receive, could help detect colorectal cancer. This antibody targets and attaches to cancer cells in the colon. In patient tests, it located tumors more effectively than other antibodies targeting different proteins. As a result, 124I-huA33 can accurately identify cancer cells, aiding doctors in visualizing them with PET scans, a type of imaging test. These findings provide early evidence that 124I-huA33 might be a useful tool for detecting colorectal cancer. ^{1 2 6 7 8}

Who Is on the Research Team?

Neeta Pandit-Taskar, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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

My colorectal cancer was confirmed at MSKCC.

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

I am a woman who can have children and have a negative pregnancy test.

Exclusion Criteria

I do not have severe heart disease.

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

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

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3394182/

124I-huA33 Antibody PET of Colorectal Cancer - PMC In this study, we took advantage of quantitative PET to evaluate 124I huA33 targeting, biodistribution, and safety in patients with colorectal cancer. We also ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3394180/

124I-huA33 Antibody Uptake Is Driven by A33 Antigen ... We performed a clinical study of 124I-huA33 PET in patients with colorectal cancer. In 15 patients, for whom surgery was prescheduled as a standard of care, a ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT00199862?term=AREA%5BSponsorSearch%5D(%22Ludwig%20Institute%22)&rank=4

Safety Study of Radio-labeled huA33 Antibody in ... The purpose of this study is to determine whether our drug, 124I-huA33, can safely detect colorectal cancer. Detailed Description. This is an ...

4. jnm.snmjournals.org jnm.snmjournals.org/content/jnumed/42/5/764.full.pdf

Grafted Humanized A33 Monoclonal Antibody The values for 124I-huA33 localization to tumors are greater when compared with 124I-labeled anti- bodies targeting placental alkaline phosphatase (11) and.

5. researchgate.net researchgate.net/publication/280241749_PET-based_compartmental_modeling_of_124I-A33_antibody_quantitative_characterization_of_patient-specific_tumor_targeting_in_colorectal_cancer

PET-based compartmental modeling of 124I-A33 antibody We describe a novel, nonlinear compartmental model using PET-derived data to determine the "best-fit" parameters and model-derived quantities ...

6. clinicaltrial.be clinicaltrial.be/en/details/13751?per_page=20&only_recruiting=0&enrolling_by_invitation=1&active_not_recruiting=1&completed=0&only_eligible=0&only_active=0

Safety Study of Radio-labeled huA33 Antibody in Colorecta... This is an open-label, pilot study of a single 4mCi-10mCi/10mg IV dose of 124I-huA33 in patients with colorectal cancer.

7. jnm.snmjournals.org jnm.snmjournals.org/content/52/12/1878

124I-huA33 Antibody Uptake Is Driven by A33 Antigen ... The primary aim of this analysis was to examine the quantitative features of antibody–antigen interactions in tumors and normal tissue after ...

8. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT00199862/

Trial | NCT00199862 The purpose of this study is to determine whether our drug, 124I-huA33, can safely detect colorectal cancer. ... This is an open-label, pilot study of a single ...