Actinium 225 Anti-CEA Antibody for Colorectal Cancer

Overseen by Jeffrey Wong

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: City of Hope Medical Center

Must not be taking: Investigational agents

Disqualifiers: Uncontrolled illness, Brain metastasis, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests a new treatment for advanced colorectal cancer using an antibody linked to a radioactive substance. The treatment targets and kills cancer cells by delivering radiation directly to them. It aims to find the safest dose and understand its effects on patients.

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.

What data supports the effectiveness of the treatment Actinium Ac 225-DOTA-anti-CEA Monoclonal Antibody M5A for colorectal cancer?

The effectiveness of the treatment is indirectly supported by a study on a similar antibody, Yttrium-90-DOTA-M5A, which showed potential in treating cancers that produce carcinoembryonic antigen (CEA), with some patients experiencing stable disease and significant decreases in CEA levels. Additionally, the M5A antibody has been studied for its ability to target CEA, a marker often found in colorectal cancer, suggesting its potential utility in this context. ^{1 2 3 4 5}

What safety data exists for Actinium 225 Anti-CEA Antibody treatment?

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 some patients developed an immune response to the treatment. This suggests that while the treatment has potential, it may cause significant side effects in some individuals. ^{1 2 3 6 7}

What makes the drug Actinium Ac 225-DOTA-anti-CEA Monoclonal Antibody M5A unique for colorectal cancer?

This drug is unique because it combines a radioactive element, Actinium-225, with an antibody that specifically targets carcinoembryonic antigen (CEA), a protein often found in high levels on colorectal cancer cells. This allows for targeted radiation therapy, potentially minimizing damage to healthy tissues compared to traditional treatments. ^{3 4 5 8 9}

Research Team

Jeffrey Wong

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Actinium Ac 225-DOTA-anti-CEA Monoclonal Antibody M5A (Monoclonal Antibodies)
• Biospecimen Collection (Procedure)

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.

Participant Groups

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+

Robert Stone

City of Hope Medical Center

Chief Executive Officer since 2014

Juris Doctorate from the University of Chicago, Bachelor's degree in Political Science from the University of Redlands

Sumanta (Monty) Pal

City of Hope Medical Center

Chief Medical Officer since 2023

MD

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

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]

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]

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]

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 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]

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]

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]

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]

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]

References

1. United States 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. [2021]

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

Radioimmunoimaging of liver metastases with PET using a 64Cu-labeled CEA antibody in transgenic mice. [2021]

3. China pubmed.ncbi.nlm.nih.gov

[Radioimmunodetection of 188Re-labeled anti-carcinoembryonic antigen chimeric antibody in nude mice bearing human colon carcinoma]. [2015]

4. China (Republic : 1949- ) pubmed.ncbi.nlm.nih.gov

Immunological characteristics of monoclonal antibodies against human carcinoembryonic antigen (CEA). [2015]

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

Detection efficiency of colorectal carcinoma recurrence using technetium pertechnetate-anti-carcinoembryonic antigen monoclonal antibody BW 431/26. [2019]

6. United States 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. [2019]

7. China pubmed.ncbi.nlm.nih.gov

Radioimmunotherapy with 153Sm-CEA monoclonal antibody in nude mice bearing human colon carcinoma: an experimental study. [2013]

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

Radiolocalisation of an anti-CEA monoclonal antibody (FO23C5) and its fragments in a colon carcinoma xenograft model. [2017]

9. China pubmed.ncbi.nlm.nih.gov

[Expression of tumor-associated antigen LEA and its significance for pathological diagnosis]. [2015]