Investigational Scan + Chemotherapy/Radiotherapy for Rectal Cancer

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: City of Hope Medical Center

Must not be taking: Investigational agents

Disqualifiers: Uncontrolled illness, Active infection, Pregnancy, others

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

Compensation: Varies

Number of Visits: 2

15 Participants Needed

Trial Summary

What is the purpose of this trial?

This early phase I trial investigates how well 64Cu-labeled M5A antibody scan works in assessing tumor activity before and after patients with rectal cancer that has spread to nearby tissue or lymph nodes (locally advanced) who are undergoing chemotherapy and radiotherapy. Using 64Cu-labeled M5A positron emission tomography imaging may play a significant role in imaging patients with colorectal cancer.

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 complete any prior chemotherapy, immunotherapy, or radiotherapy at least 2 weeks before starting the trial. You also cannot be on any other investigational drugs or treatments during the trial.

What data supports the effectiveness of the treatment Copper Cu 64 Anti-CEA Monoclonal Antibody M5A for rectal cancer?

Research shows that the Copper Cu 64 Anti-CEA Monoclonal Antibody M5A has been effective in detecting tumors in patients with rectal cancer, as it demonstrated a high concordance with biopsy findings and standard imaging methods. This suggests it could be useful in identifying the extent of the disease and assessing response to chemotherapy and radiotherapy. ^{1 2 3 4 5}

Is the investigational scan with Copper Cu 64 Anti-CEA Monoclonal Antibody M5A safe for humans?

In a pilot study, the Copper Cu 64 Anti-CEA Monoclonal Antibody M5A was used in patients with certain cancers, and it showed promise in detecting tumors without reported safety issues. However, detailed safety data specific to humans is limited, and further studies are needed to fully understand its safety profile. ^{1 2 3 4 5}

How does the investigational scan combined with chemotherapy/radiotherapy for rectal cancer differ from other treatments?

This treatment is unique because it uses a special PET scan with a radiolabeled antibody that targets carcinoembryonic antigen (CEA), which is often present in rectal cancer. This scan helps to better detect and assess the extent of the cancer, potentially improving the precision of chemotherapy and radiotherapy by providing detailed imaging of the tumor. ^{1 2 3 4 6}

Research Team

Jeffrey Wong

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

This trial is for adults with advanced rectal cancer that can be detected on scans and who are scheduled for chemotherapy, radiation, then surgery. They must have completed any previous treatments at least two weeks before the study starts and agree to use contraception. Pregnant women, those with allergies to similar drugs, uncontrolled illnesses or infections, or taking other experimental treatments cannot participate.

Inclusion Criteria

Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for six months following duration of study participation

My recent scans and blood tests were done within the last 2 months.

I am scheduled for chemo, radiation, and surgery for my cancer.

Exclusion Criteria

Subjects who may not be able to comply with the safety monitoring requirements of the study

I am not currently on any experimental treatments or other cancer therapies.

I will stop breastfeeding if treated with 64Cu-M5A.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-treatment Imaging

Participants receive 64Cu labeled M5A antibody and undergo PET scan before standard of care chemo/radiotherapy

1 week

1 visit (in-person)

Chemoradiotherapy

Participants undergo standard of care chemotherapy and radiotherapy

6-8 weeks

Post-treatment Imaging

Participants receive 64Cu labeled M5A antibody and undergo PET scan after standard of care chemo/radiotherapy

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2-3 months

Treatment Details

Interventions

• Copper Cu 64 Anti-CEA Monoclonal Antibody M5A

Trial Overview The trial is testing a new imaging technique using a scan called 64Cu-labeled M5A antibody PET/CT to see how well it shows tumor activity in patients undergoing standard chemo and radiotherapy for locally advanced rectal cancer.

Participant Groups

Group I: Treatment (64Cu labeled M5A antibody and imaging) Experimental Treatment 2 Interventions

Patients receive 64Cu labeled M5A antibody IV over 5 minutes on day 0 pre standard of care chemo/radiotherapy and on day 0 post chemo/radiotherapy. Patients also undergo 64Cu-M5A PET scan on day 1 pre chemo/radiotherapy and on day 1 post chemo/radiotherapy.

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+

Findings from Research

67Cu-labelled antibodies demonstrate superior tumor uptake and persistence compared to radioiodinated antibodies, making them a promising option for radioimmunotherapy in cancers like lymphoma and colon carcinoma.

While 67Cu-labelled antibodies show advantages in tumor targeting, they also result in higher radiation doses to the liver compared to 131I-labelled antibodies, highlighting the need for careful evaluation in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Copper-67 as a therapeutic nuclide for radioimmunotherapy. Novak-Hofer, I., Schubiger, PA.[2006]

Copper-64-labeled monoclonal antibodies (mAbs) show effective tumor control in cancer models, with the internalizing antibody cBR96 demonstrating rapid tumor uptake, reaching 35.4% ID/g by 24 hours, compared to the noninternalizing antibody cT84.66, which peaked at 43.8% ID/g but with a slower accumulation.

Both antibodies had similar biodistributions and tumor dosimetry, allowing for a direct comparison of their therapeutic effects, indicating that internalization may not be the only factor influencing the efficacy of radioimmunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative uptakes and biodistributions of internalizing vs. noninternalizing copper-64 radioimmunoconjugates in cell and animal models of colon cancer. Bryan, JN., Jia, F., Mohsin, H., et al.[2016]

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 pilot study involving 20 patients with CEA-expressing cancers, the radiolabeled antibody 64Cu-DOTA-hT84.66-M5A showed promising results in detecting tumors, particularly in patients with locally advanced rectal cancer and medullary thyroid cancer, with a high concordance between PET scan results and biopsy findings.

The study indicated that 64Cu-DOTA-hT84.66-M5A could identify tumors not visible on standard imaging methods, suggesting its potential as a valuable tool for assessing tumor response to therapies and guiding treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-In-Human Pilot PET Immunoimaging Study of 64Cu-Anti-Carcinoembryonic Antigen Monoclonal Antibody (hT84.66-M5A) in Patients with Carcinoembryonic Antigen-Producing Cancers. Wong, JYC., Yamauchi, DM., Adhikarla, V., et al.[2023]

Copper-64 can effectively target tumor cell nuclei, with significantly higher nuclear uptake observed in p53-positive colorectal cancer cells compared to p53-negative cells, suggesting that the presence of the p53 protein enhances the delivery of this radiopharmaceutical.

Both non-specific and receptor-mediated mechanisms contribute to the nuclear localization of Copper-64, indicating its potential for effective targeted radiotherapy in cancers expressing the p53 tumor suppressor protein.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of p53 in the trafficking of copper-64 to tumor cell nuclei. Eiblmaier, M., Meyer, LA., Anderson, CJ.[2020]

A genetically engineered minibody derived from the anti-CEA antibody showed high uptake in CEA-positive tumors during PET imaging, indicating its potential for effective tumor targeting with a significant target/background ratio of 3-4:1.

The use of copper-64 as a short-lived radionuclide for labeling these engineered antibody fragments allows for rapid imaging, making it a promising approach for enhancing the detection of tumors compared to traditional whole antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-resolution microPET imaging of carcinoembryonic antigen-positive xenografts by using a copper-64-labeled engineered antibody fragment. Wu, AM., Yazaki, PJ., Tsai, Sw., et al.[2018]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Copper-67 as a therapeutic nuclide for radioimmunotherapy. [2006]

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

Comparative uptakes and biodistributions of internalizing vs. noninternalizing copper-64 radioimmunoconjugates in cell and animal models of colon cancer. [2016]

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

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

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

First-In-Human Pilot PET Immunoimaging Study of 64Cu-Anti-Carcinoembryonic Antigen Monoclonal Antibody (hT84.66-M5A) in Patients with Carcinoembryonic Antigen-Producing Cancers. [2023]

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

The role of p53 in the trafficking of copper-64 to tumor cell nuclei. [2020]

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

High-resolution microPET imaging of carcinoembryonic antigen-positive xenografts by using a copper-64-labeled engineered antibody fragment. [2018]