Actinium 225 Anti-CEA Antibody for Colorectal Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must not be taking: Investigational agents

Disqualifiers: Uncontrolled illness, Brain metastasis, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new treatment for advanced colorectal cancer that has spread to other parts of the body. The treatment combines a special antibody, a type of protein, with a radioactive substance called actinium 225. This combination targets and kills specific cancer cells that produce a protein known as CEA. Individuals with CEA-positive colorectal cancer who have exhausted standard treatment options might be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive it.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must not be on any other investigational drugs or undergoing chemotherapy, radiation, or biological therapy. You should discuss your current medications with the trial team to ensure they don't interfere with the study.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that the treatment, Actinium Ac 225-DOTA-anti-CEA Monoclonal Antibody M5A, remains in the early stages of testing for safety and side effects. As a result, limited information exists on how well people tolerate it or what side effects it might cause. This treatment is a specialized antibody that targets certain cancer cells and delivers a radioactive substance directly to them.

Although specific safety results for this treatment are not yet available, similar treatments have demonstrated some side effects, primarily related to blood issues. This suggests that the current trial seeks to determine the optimal dose that minimizes these effects. As an early phase trial, it primarily focuses on understanding these safety aspects.

Participants in this type of study assist researchers in learning more about the treatment's safety and potential benefits. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for colorectal cancer, which typically involve chemotherapy or targeted therapies like bevacizumab and cetuximab, the Actinium Ac 225-DOTA-anti-CEA Monoclonal Antibody M5A introduces a novel approach. This treatment uses a radioactive isotope, Actinium-225, attached to a monoclonal antibody that specifically targets the CEA protein found on cancer cells. By delivering radiation directly to the cancer cells, it aims to minimize damage to healthy tissues. Researchers are excited about this treatment because it offers a targeted mechanism that could potentially increase effectiveness while reducing side effects compared to conventional therapies.

What evidence suggests that this treatment might be an effective treatment for colorectal cancer?

Research has shown that the Actinium Ac 225-DOTA-anti-CEA Monoclonal Antibody M5A, administered to participants in this trial, targets cancer cells with a protein called CEA, often abundant on colorectal cancer cells. This treatment employs a special type of antibody, akin to a guided missile, to deliver the radioactive substance actinium 225 directly to the cancer cells. The radioactivity can kill the cancer cells while mostly sparing nearby healthy cells. Early results suggest that this targeted method may effectively treat advanced colorectal cancer that has spread. ^{1 2 3 4 6}

Who Is on the Research Team?

Jeffrey Wong

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

Adults with advanced colorectal cancer that produces CEA and has spread, who have no standard treatment options left. They must be in good enough health to participate, not pregnant or breastfeeding, use contraception, and have finished any previous cancer treatments at least 4 weeks ago.

Inclusion Criteria

I finished my last cancer treatment at least 4 weeks ago and have recovered from its side effects.

My disease is advanced and there's no standard treatment that works for me.

My kidney function is good, with creatinine levels at or below 1.5 mg/dl.

Exclusion Criteria

My brain cancer has returned or worsened, but I've had treatment for it and either improved or remained stable for at least 4 weeks.

I am not pregnant or breastfeeding.

I have had radiation on more than half of my bone marrow.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive Ac225-DOTA-M5A intravenously over 25 minutes on day 1

1 day

1 visit (in-person)

Follow-up

Participants are monitored weekly for safety and effectiveness after treatment

6-10 weeks

Weekly visits (in-person)

Long-term follow-up

Medical records are reviewed for long-term outcomes

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Actinium Ac 225-DOTA-anti-CEA Monoclonal Antibody M5A
• Biospecimen Collection

Trial Overview The trial is testing Ac225-DOTA-M5A, a radioactive drug designed to target and kill CEA positive cancer cells. It's a phase I study which means they're looking for the safest dose with the fewest side effects.

How Is the Trial Designed?

Group I: Treatment (Ac225-DOTA-M5A) Experimental Treatment 2 Interventions

Patients receive Ac225-DOTA-M5A IV over 25 minutes on day 1.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a phase I trial involving 18 patients with advanced CEA-producing cancers, the maximum tolerated dose (MTD) of the monoclonal antibody 90Y-DOTA-M5A was established at 10 mCi/m2 due to dose-limiting hematopoietic toxicities, indicating a need for careful monitoring of blood cell levels during treatment.

The study showed promising results with 10 out of 16 patients achieving stable disease after 3 months, and two patients experiencing significant reductions in CEA levels, suggesting that 90Y-DOTA-M5A could be an effective therapeutic option with lower immunogenicity compared to traditional antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of Yttrium-90 Radiolabeled M5A Anti-Carcinoembryonic Antigen Humanized Antibody in Patients with Advanced Carcinoembryonic Antigen Producing Malignancies. Akhavan, D., Yazaki, P., Yamauchi, D., et al.[2021]

In a study involving 31 patients, the anti-carcinoembryonic antigen (CEA) antibody labeled with technetium (Tc-99m-BW 431/26) demonstrated a high sensitivity of 96.8% and specificity of 100% for detecting colorectal cancer recurrence, making it a reliable diagnostic tool.

The radioimmunoimaging procedure was safe and easy to perform, with no adverse side effects reported, highlighting its potential as a valuable addition to the diagnostic workup for patients with rising CEA levels of unknown origin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection efficiency of colorectal carcinoma recurrence using technetium pertechnetate-anti-carcinoembryonic antigen monoclonal antibody BW 431/26. Zwas, ST., Goshen, E., Rath, P., et al.[2019]

The (64)Cu-DOTA-labeled M5A antibody effectively targets and images CEA-positive liver metastases in mice, showing significantly higher uptake in tumors compared to healthy liver tissue and CEA-negative metastases, indicating its potential for accurate cancer detection.

This study suggests that the M5A antibody could be a valuable tool for staging colorectal cancer and guiding treatment decisions, including radioimmunotherapy, based on its ability to differentiate between cancerous and non-cancerous tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radioimmunoimaging of liver metastases with PET using a 64Cu-labeled CEA antibody in transgenic mice. Nittka, S., Krueger, MA., Shively, JE., et al.[2021]

In a study involving 15 nude mice with human colon carcinoma, the 153Sm-labeled CEA monoclonal antibody (mAb) demonstrated a significant anti-tumor effect, achieving a tumor inhibition rate of 74.29% after 4 weeks, compared to only 15.90% for the control group receiving 153SmCl3.

Histopathological analysis showed tumor necrosis in the therapy group, indicating effective radioactive damage, while no significant weight changes were observed across all groups, suggesting that the treatment was well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radioimmunotherapy with 153Sm-CEA monoclonal antibody in nude mice bearing human colon carcinoma: an experimental study. Li, GP., Zhang, H., Zhu, CM.[2013]

Four monoclonal antibodies (MAbs) against human carcinoembryonic antigen (CEA) were developed, with MAb C27 showing the highest affinity for CEA and no cross-reactivity with normal human colon tissues, indicating its specificity for cancer detection.

MAb C27 demonstrated strong immunofluorescence staining in colorectal cancer cells, correlating well with CEA content, and showed 100% positivity in colorectal carcinoma tissues, suggesting its potential use in immunodetection and radiolocalization of colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunological characteristics of monoclonal antibodies against human carcinoembryonic antigen (CEA). Tsai, LC., Wang, FM., Pan, LC., et al.[2015]

In a Phase I/II study involving 15 patients with metastatic medullary thyroid carcinoma, the monoclonal antibody (131)I-MN-14 F(ab)2 demonstrated safety and a maximum tolerated dose of 180 cGy to the bone marrow, with myelosuppression being the main dose-limiting toxicity.

The treatment resulted in a median 55% reduction in tumor markers for seven patients, and 11 out of 12 assessable patients maintained stable disease for 3 to over 26 months, indicating promising antitumor activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II trial of (131)I-MN-14F(ab)2 anti-carcinoembryonic antigen monoclonal antibody in the treatment of patients with metastatic medullary thyroid carcinoma. Juweid, ME., Hajjar, G., Swayne, LC., et al.[2019]

The 188Re-labeled anti-CEA chimeric antibody demonstrated high radiochemical purity and specific tumor uptake in nude mice with human colon carcinoma, indicating its potential for effective imaging and targeting of tumors.

Compared to the parent McAb C50, the chimeric antibody showed similar radioimmunodetection effects while having reduced immunogenicity, making it a promising option for clinical applications in colon carcinoma diagnosis and therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Radioimmunodetection of 188Re-labeled anti-carcinoembryonic antigen chimeric antibody in nude mice bearing human colon carcinoma]. Zhao, ZG., Ran, YL., Zheng, R., et al.[2015]

The study evaluated the expression of the colorectal carcinoma-associated antigen LEA in 170 colorectal cancer specimens and found that it had a higher positive rate in well-differentiated cancers (100%) compared to CEA, indicating its potential as a more specific marker for colorectal carcinoma.

LEA demonstrated lower positivity in non-cancerous tissues compared to CEA, suggesting it may provide better specificity for diagnosing colorectal cancer, making it a valuable biological tumor marker for assessing the malignancy degree.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Expression of tumor-associated antigen LEA and its significance for pathological diagnosis]. Feng, H., Song, JD.[2015]

The newly developed monoclonal antibody FO23C5 shows comparable effectiveness to existing anti-CEA antibodies in targeting human colon cancer, as demonstrated in a xenograft model.

F(ab')2 fragments of FO23C5 achieved the best tumor-to-normal tissue ratios, suggesting they may be more effective for cancer targeting than intact IgG or Fab fragments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiolocalisation of an anti-CEA monoclonal antibody (FO23C5) and its fragments in a colon carcinoma xenograft model. Rowlinson, G., Paganelli, G., Snook, D., et al.[2017]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05204147

NCT05204147 | Actinium 225 Labeled Anti-CEA Antibody ... Ac225-DOTA-M5A is a humanized monoclonal anti-CEA antibody, linked to a radioactive agent called actinium 225. M5A attaches to CEA positive cancer cells in a ...

2. cancer.gov cancer.gov/publications/dictionaries/cancer-drug/def/actinium-ac-225-dota-anti-cea-monoclonal-antibody-m5a

actinium Ac 225-DOTA-anti-CEA monoclonal antibody M5A Upon administration, the monoclonal antibody moiety of actinium Ac 225-DOTA-anti-CEA monoclonal antibody M5A specifically targets and binds to CEA, thereby ...

3. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT05204147/

Trial | NCT05204147 This phase I study tests the safety, side effects, and best dose of Ac225-DOTA-M5A in treating patients with CEA positive colorectal cancer that has spread to ...

4. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/actinium-ac-225-dota-anti-cea-monoclonal-antibody-m5a?pn=1

Clinical Trials Using Actinium Ac 225-DOTA-anti-CEA ... Review the clinical trials studying actinium ac 225-dota-anti-cea monoclonal antibody m5a on this list and use the filters to refine the results by age and ...

5. theranostictrials.org theranostictrials.org/studies/cl74bp9il0256ajjf2xbfykg2/study/NCT05204147

NCT05204147 This phase I study tests the safety, side effects, and best dose of Ac225-DOTA-M5A in treating patients with CEA positive colorectal cancer that has spread ...

6. withpower.com withpower.com/trial/phase-1-advanced-colorectal-carcinoma-6-2022-204d8

Actinium 225 Anti-CEA Antibody for Colorectal Cancer The safety data for a similar treatment, Yttrium-90-DOTA-M5A, showed that the maximum tolerated dose was determined based on blood-related side effects, and ...