CCR2-Targeted Imaging for Pancreatic Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Farrokh Dehdashti, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Washington University School of Medicine

Disqualifiers: Other invasive malignancies, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

Currently there is no clinical biomarker that can be used to select patients for CCR2-targeted therapy and to monitor response to such therapy. Considering the toxicity and the rate of response to CCR2-targeted therapy, it is crucial to be able to identify patients who may not response to this therapy in order to avoid the morbidity and expense associated with ineffective therapy. Therefore, the combination of the novel CCR2 imaging agent with the novel CCR2-targeted therapy in this trial is of great importance to promote science while prolonging the life and its quality in patients with PDAC. The investigators also believe that this combination will make substantial contributions to the fields of cancer immunotherapy and tumor monocyte/macrophage biology. Moreover, this imaging agent has the potential to not only facilitate development and testing of future CCR2-targeted therapeutic agents but also serve as a prescreen tool to select appropriate patients for imaging guided treatment.

Will I have to stop taking my current medications?

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 data supports the effectiveness of the treatment 64Cu-DOTA-ECLIi for pancreatic cancer?

Research on similar treatments shows that targeting the CCR2 receptor with copper-based nanoparticles can help detect and treat pancreatic cancer in animal models. These nanoparticles, when used with imaging techniques, have shown promise in accurately identifying cancer and delivering chemotherapy effectively, which suggests potential for the 64Cu-DOTA-ECLIi treatment. ^{1 2 3 4 5}

Is the CCR2-targeted imaging agent safe for humans?

The CCR2-targeted imaging agent, tested in mice, showed minimal toxicity and was cleared efficiently by the kidneys, suggesting it may be safe. However, specific human safety data is not available from the provided research. ^{1 2 3 5 6}

How does the CCR2-targeted imaging treatment for pancreatic cancer differ from other treatments?

This treatment uses CCR2-targeted copper nanoparticles to deliver the chemotherapy drug gemcitabine directly to pancreatic cancer cells, allowing for both precise imaging and targeted therapy. This dual approach is unique because it combines diagnostic imaging with treatment, potentially improving detection and effectiveness compared to traditional methods. ^{1 3 6 7 8}

Research Team

Farrokh Dehdashti, M.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for adults over 18 with early-stage pancreatic cancer scheduled for surgery, or those who've had chemo and can now have surgery. It's also open to patients with advanced stages eligible for CCR2-targeted therapy. Participants must not be pregnant/nursing and should agree to a pregnancy test if applicable.

Inclusion Criteria

My pancreatic cancer is advanced and I am scheduled for chemotherapy.

I have advanced pancreatic cancer and am considering or have agreed to a specific therapy.

I am 18 or older with early-stage pancreatic cancer and scheduled for or have had chemotherapy before surgery.

Exclusion Criteria

I cannot stay still for 90 minutes during a scan.

I have not had any cancer other than non-melanoma skin cancer in the past 5 years.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging and Pretherapy Assessment

Participants undergo 64Cu-DOTA-ECL1i-PET/CT imaging to assess CCR2 expression and tumor uptake prior to therapy

1 week

1 visit (in-person)

Treatment

Participants receive either standard of care chemotherapy or CCR2-targeted therapy, with additional imaging to monitor response

8 weeks

Multiple visits (in-person) for treatment and imaging

Follow-up

Participants are monitored for safety and effectiveness after treatment, including additional imaging to assess response

4 weeks

Treatment Details

Interventions

• 64Cu-DOTA-ECLIi (Imaging Agent)

Trial Overview The trial tests a new imaging agent (64Cu-DOTA-ECLIi) combined with PET/CT scans to select patients for CCR2-targeted therapy and monitor their response. This could help avoid ineffective treatments in pancreatic cancer by identifying non-responders early on.

Participant Groups

Group I: Cohort 2: CCR2-Targeted Therapy Experimental Treatment 2 Interventions

* Locally advanced or borderline resectable pancreatic cancer * Biopsy per therapeutic protocol (if available tissue to be used for CCR2 expression) * 64Cu-DOTA-ECL1i-PET/CT imaging pretherapy * 2 cycles of CCR2-targeted therapy * Biopsy per therapeutic protocol (tissue to be used for CCR2 expression) --Additional 64Cu-DOTA-ECL1i-PET/CT imaging after 2 cycles of therapy

Group II: Cohort 1b: Standard of Care Treatment Chemotherapy Experimental Treatment 2 Interventions

* Borderline resectable, locally advanced/metastatic or recurrent pancreatic cancer * Standard of care diagnostic biopsy (if available tissue to be used for CCR2 expression) * 64Cu-DOTA-ECL1i-PET/CT imaging pretherapy * Treatment with any standard of care (SOC) chemotherapy * Additional 64Cu-DOTA-ECL1i-PET/CT imaging for patients with positive scan at baseline/early therapy at the time of standard of care follow-up imaging appointment --Additional 64Cu-DOTA-ECL1i-PET/CT imaging for patients with negative scan at baseline/early therapy at time recurrence is diagnosed by any standard imaging modality

Group III: Cohort 1a: Treatment Whipple/Surgical Procedure/Surgery following neoadjuvant therapy Experimental Treatment 2 Interventions

* Early-staged localized pancreatic cancer * Standard of care diagnostic biopsy * 64Cu-DOTA-ECL1i-PET/CT imaging - immediately after the dynamic study * Receive treatment with upfront surgery such as whipple procedure or surgery following neoadjuvant therapy.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Washington University School of Medicine Saint Louis, MO

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2027

Recruited

2,353,000+

David H. Perlmutter

Washington University School of Medicine

Chief Executive Officer since 2015

MD from Washington University School of Medicine

Paul Scheel

Washington University School of Medicine

Chief Medical Officer since 2022

MD from Washington University School of Medicine

National Cancer Institute (NCI)

Collaborator

Trials

14080

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

Engineered CCR2-targeting ultrasmall copper nanoparticles (Cu@CuOx) can effectively detect pancreatic ductal adenocarcinoma (PDAC) using positron emission tomography (PET) imaging, providing a sensitive method for early diagnosis in mouse models.

These nanoparticles not only facilitate imaging but also deliver the chemotherapy drug gemcitabine, significantly suppressing tumor progression and prolonging survival in treated mice, indicating their potential as a dual diagnostic and therapeutic tool.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CC Chemokine Receptor 2-Targeting Copper Nanoparticles for Positron Emission Tomography-Guided Delivery of Gemcitabine for Pancreatic Ductal Adenocarcinoma. Zhang, X., Detering, L., Sultan, D., et al.[2023]

The study demonstrated that the copper transporter 1 (CTR1) is overexpressed in various lung cancer cell lines, and the uptake of the tracer copper (II)-64 chloride (64CuCl2) is directly related to the levels of CTR1 expression, indicating its potential for targeted imaging.

Small animal PET imaging confirmed that 64CuCl2 can effectively visualize CTR1 expression in lung cancer tumors, suggesting it could be a valuable tool for PET imaging in clinical lung cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical PET imaging study of lung cancer with 64CuCl2. Wang, Q., Song, D., Ma, X., et al.[2022]

The minigastrin analogue PP-F11, when radiolabeled with (68)Ga or (111)In, effectively targets CCK-2 receptors in tumors, showing high tumor-to-background ratios in imaging studies, which suggests its potential for accurate tumor visualization.

(68)Ga-DOTA-PP-F11 demonstrated the best performance for PET/CT imaging of CCK-2 receptor positive tumors, indicating it could be a promising radiopharmaceutical for clinical use in detecting cancers like small cell lung cancer and medullary thyroid carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PET and SPECT imaging of a radiolabeled minigastrin analogue conjugated with DOTA, NOTA, and NODAGA and labeled with (64)Cu, (68)Ga, and (111)In. Roosenburg, S., Laverman, P., Joosten, L., et al.[2022]

Copper-64 chloride (64CuCl2) is a promising radiotracer for cancer imaging using PET, showing safety in humans and effective imaging for various cancers including prostate, bladder, and glioblastoma.

The dual emission of β+ and β- particles from 64CuCl2 suggests its potential not only for imaging but also for therapeutic applications in treating copper-avid tumors, especially with the development of the therapeutic copper-67 radionuclide for combined imaging and therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent Advances in Cancer Imaging with 64CuCl2 PET/CT. Peng, F.[2023]

Copper-64 (64Cu) is a promising PET/CT tracer for diagnosing various cancers, including prostate cancer and glioblastoma, due to its ability to target copper-avid tumors and its favorable nuclear properties for both imaging and therapy.

Studies indicate that 64CuCl2 is safe in terms of radiation and toxicology, making it a viable option for theragnostic applications in oncology, particularly for imaging and potentially treating cancers like hepatocellular carcinoma and malignant melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting Copper in Cancer Imaging and Therapy: A New Theragnostic Agent. Capriotti, G., Piccardo, A., Giovannelli, E., et al.[2023]

References

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

CC Chemokine Receptor 2-Targeting Copper Nanoparticles for Positron Emission Tomography-Guided Delivery of Gemcitabine for Pancreatic Ductal Adenocarcinoma. [2023]

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

Radioimmunotherapy of human pancreatic cancer xenografts in NOD-scid mice with [64Cu]Cu-NOTA-panitumumab F(ab')2 alone or combined with radiosensitizing gemcitabine and the PARP inhibitor, rucaparib. [2022]

3. Japan pubmed.ncbi.nlm.nih.gov

Preclinical PET imaging study of lung cancer with 64CuCl2. [2022]

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

ImmunoPET Imaging of CD47 with VHH-Derived Tracers in Pancreatic Cancers. [2023]

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

PET and SPECT imaging of a radiolabeled minigastrin analogue conjugated with DOTA, NOTA, and NODAGA and labeled with (64)Cu, (68)Ga, and (111)In. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

Recent Advances in Cancer Imaging with 64CuCl2 PET/CT. [2023]

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

Site-specific Conjugation of 6 DOTA Chelators to a CA19-9-targeting scFv-Fc Antibody for Imaging and Therapy. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Targeting Copper in Cancer Imaging and Therapy: A New Theragnostic Agent. [2023]