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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to assess the effectiveness of rectal cancer treatments. It employs a special scan using a Copper Cu 64 Anti-CEA Monoclonal Antibody M5A (also known as the 64Cu-labeled M5A antibody) to evaluate tumor activity before and after chemotherapy and radiotherapy. The aim is to enhance imaging for patients with rectal cancer that has spread to nearby tissues or lymph nodes. Individuals with rectal cancer scheduled for chemotherapy and radiotherapy, whose cancer produces a protein called CEA, may be suitable candidates for this trial. As an Early Phase 1 trial, this research seeks to understand how the treatment functions in people, offering participants the chance to be among the first to experience this innovative imaging approach.

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 prior data suggests that this scan is safe for assessing tumor activity?

Research has shown that the Copper Cu 64 Anti-CEA Monoclonal Antibody M5A is under investigation for its potential to detect tumors. This investigational scan uses a special imaging technique called PET, or positron emission tomography, which helps doctors see how organs and tissues function. Early results suggest that the 64Cu-labeled M5A antibody shows promise in identifying tumors, particularly in patients with certain cancers like rectal cancer.

Regarding safety, this is an early phase I trial. Researchers are primarily focused on understanding its safety and tolerability. In previous studies, similar treatments have been used without major safety concerns. However, as this is still in the early testing stages, some unknowns may exist. Participants should discuss the potential risks and benefits with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for rectal cancer involve standard chemotherapy and radiotherapy, which target cancer cells broadly. But this investigational approach uses the Copper Cu 64 Anti-CEA Monoclonal Antibody M5A to offer a unique twist. This treatment involves a radiolabeled antibody that specifically targets carcinoembryonic antigen (CEA), a protein often found on cancer cells, providing a more precise attack on the tumor. By combining this targeted approach with a PET scan, doctors can visually track the response of the tumor to treatment in real-time. Researchers are excited because this method could lead to more personalized and effective treatment plans, potentially improving outcomes for patients.

What evidence suggests that this scan is effective for assessing tumor activity in rectal cancer?

In this trial, participants will receive the Copper Cu 64 Anti-CEA Monoclonal Antibody M5A, used with PET scans to effectively detect tumors in patients with certain types of cancer. A small study with 20 patients showed that this method successfully identified tumors that might not be visible with other techniques. This treatment employs a special antibody targeting specific proteins on cancer cells, enhancing the visibility of the cancer. While primarily used to diagnose and evaluate cancer, these early results suggest potential usefulness in managing rectal cancer. ^{1 3 6 7 8}

Who Is on the Research Team?

Jeffrey Wong

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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-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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02293954

Copper Cu 64 Anti-CEA Monoclonal Antibody M5A PET in ... Diagnostic procedures, such as copper Cu 64 anti-CEA monoclonal antibody M5A PET, may help find and diagnose CEA positive cancer that may not be detected by ...

2. clinicaltrial.be clinicaltrial.be/en/details/32562?per_page=100&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

An Investigational Scan (64Cu-Labeled M5A Antibody) in ... PRIMARY OBJECTIVE: I. To determine if the Copper Cu 64 anti-carcinoembryonic antigen (CEA) monoclonal antibody M5A (64Cu labeled M5A ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02293954?term=AREA%5BConditionSearch%5D(%22Gallbladder%20Disease%22)%20AND%20AREA%5BInterventionSearch%5D(%22antibodies%22)&rank=2

Copper Cu 64 Anti-CEA Monoclonal Antibody M5A PET in ... This pilot clinical trial studies copper Cu 64 anti-carcinoembryonic antigen (CEA) monoclonal antibody M5A positron emission tomography (PET) in diagnosing ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-14005

An Investigational Scan (64Cu-Labeled M5A Antibody) in ... 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 ...

5. withpower.com withpower.com/trial/copper-cu-64-anti-cea-monoclonal-antibody-m5a-pet-scan-for-cancer-1ff58

Copper Cu 64 Anti-CEA Monoclonal Antibody M5A PET Scan for ... 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 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05245786

An Investigational Scan (64Cu-Labeled M5A Antibody) in ... 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 ...

7. centerwatch.com centerwatch.com/clinical-trials/listings/NCT02293954/copper-cu-64-anti-cea-monoclonal-antibody-m5a-pet-in-diagnosing-patients-with-cea-positive-cancer?activelyRecruiting=false&page=661&id=25005&slug=carcinoma

Copper Cu 64 Anti-CEA Monoclonal Antibody M5A PET in ... Diagnostic procedures, such as copper Cu 64 anti-CEA monoclonal antibody M5A PET, may help find and diagnose CEA positive cancer that may not be ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36154291/

First-In-Human Pilot PET Immunoimaging Study of 64Cu ... 64 Cu-DOTA-hT84.66-M5A demonstrates promise in tumor detection, particularly in patients with locally advanced rectal cancer and medullary thyroid cancer.