CCR2-Targeted Imaging for Pancreatic Cancer

Not currently recruiting at 1 trial location

Overseen By Farrokh Dehdashti, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Washington University School of Medicine

Disqualifiers: Other invasive malignancies, others

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

Compensation: Varies

Number of Visits: 1

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to improve pancreatic cancer treatment by testing a new imaging agent (64Cu-DOTA-ECLIi) alongside a CCR2-targeted therapy. The goal is to identify patients who will benefit from this therapy, potentially enhancing their quality of life while avoiding unnecessary side effects. The trial includes different groups: one undergoing surgery, another receiving standard chemotherapy, and a third receiving the new CCR2-targeted therapy. Patients with newly diagnosed pancreatic cancer, recurrent cancer, or locally advanced cancer that can be surgically removed might be suitable candidates. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the imaging agent 64Cu-DOTA-ECL1i is under study for its ability to detect a protein called CCR2 in pancreatic cancer. This could help monitor changes in the cancer when using treatments targeting CCR2.

Currently, no specific tests exist to select patients for this therapy or to assess their response. Therefore, the imaging agent could become a valuable tool for better treatment planning. However, since this trial is in its early stages, researchers are still learning about the safety of 64Cu-DOTA-ECL1i in humans.

The imaging agent has shown promise in detecting cancer details in lab models, but there is limited information on its tolerability and side effects in people. While there is potential, more research is needed to understand its safety for human use. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they employ a novel imaging agent, 64Cu-DOTA-ECL1i, which targets the CCR2 receptor. This approach is different because it allows for precise imaging of pancreatic tumors, potentially improving the accuracy of diagnoses and the monitoring of treatment responses. Unlike traditional options that primarily rely on chemotherapy and surgery without such targeted imaging, this method could help tailor treatments more effectively to individual patients' needs. By providing detailed insights into the tumor environment, researchers hope this technique will lead to better outcomes for patients with pancreatic cancer.

What evidence suggests that this trial's treatments could be effective for pancreatic cancer?

Research has shown that the imaging agent 64Cu-DOTA-ECL1i, which targets CCR2, has potential based on early studies. It effectively detects CCR2, a protein linked to inflammation, in various disease models. In mice, this tracer demonstrated low toxicity and was quickly eliminated by the kidneys, suggesting potential safety for humans. In this trial, participants in Cohort 1a will undergo 64Cu-DOTA-ECL1i-PET/CT imaging after neoadjuvant therapy and surgery, while those in Cohort 1b will receive standard chemotherapy with imaging before and during treatment. Cohort 2 will explore CCR2-targeted therapy with imaging before and after treatment cycles. Although a clinical marker for CCR2-targeted therapy does not yet exist, this imaging agent could identify patients who might benefit from these treatments, which is crucial because some therapies can be highly toxic. The main goal is to use this imaging to guide treatment and improve outcomes for pancreatic cancer patients. ^{1 3 5 6 7}

Who Is on the Research Team?

Farrokh Dehdashti, M.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• 64Cu-DOTA-ECLIi

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.

How Is the Trial Designed?

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.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

Radioimmunotherapy (RIT) using [64Cu]Cu-NOTA-panitumumab F(ab')2 showed no significant normal tissue toxicity in non-tumor-bearing mice, indicating a safety profile for this treatment approach.

Combining RIT with gemcitabine and the PARP inhibitor rucaparib improved treatment effectiveness for pancreatic cancer xenografts, leading to longer median survival, but tumors continued to grow exponentially, suggesting that [64Cu] may not be the best choice for RIT in pancreatic cancer.

NCBI (Pubmed)

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. Boyle, AJ., Cao, PJ., Cai, Z., et al.[2022]

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]

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]

Two novel immunoPET tracers targeting CD47, [68Ga]Ga-NOTA-C2 and [89Zr]Zr-DFO-ABDC2, were developed and shown to effectively detect pancreatic ductal adenocarcinoma (PDAC) in preclinical models, indicating their potential as diagnostic tools.

The [89Zr]Zr-DFO-ABDC2 tracer demonstrated superior performance with longer circulation time and higher tumor uptake compared to [68Ga]Ga-NOTA-C2, suggesting it may be more effective for identifying CD47 expression in PDAC and guiding targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ImmunoPET Imaging of CD47 with VHH-Derived Tracers in Pancreatic Cancers. Liang, C., Huang, W., Zhang, Y., et al.[2023]

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 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]

The antibody radionuclide conjugate TE-1132, designed for targeting pancreatic cancer, showed selective tumor accumulation and effective tumor growth inhibition in mice, indicating its potential as a therapeutic option.

TE-1132 demonstrated good safety profiles, with no irreversible body weight loss or hematopoietic damage observed in treated mice, supporting its further investigation for clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Site-specific Conjugation of 6 DOTA Chelators to a CA19-9-targeting scFv-Fc Antibody for Imaging and Therapy. Chen, LA., Yu, YH., Tian, WT., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03851237

CCR2 PET for Pancreatic Cancer Imaging and Prediction ... Currently there is no clinical biomarker that can be used to select patients for CCR2-targeted therapy and to monitor response to such therapy.

2. reporter.nih.gov reporter.nih.gov/search/D8ieGRcSrEmrgaD69xmO6A/project-details/10534151

RePORT RePORTER - National Institutes of Health (NIH) | We have developed a CCR2- PET tracer (64Cu-DOTA-ECL1i) and shown its sensitivity and specificity in imaging CCR2 in multiple preclinical inflammatory disease ...

3. withpower.com withpower.com/trial/phase-1-2019-45103

CCR2-Targeted Imaging for Pancreatic Cancer The CCR2-targeted imaging agent, tested in mice, showed minimal toxicity and was cleared efficiently by the kidneys, suggesting it may be safe. However, ...

4. pubs.acs.org pubs.acs.org/doi/10.1021/acsptsci.3c00303

Chemokine Receptor 2 Targeted PET/CT Imaging Distant ... This specific cancer is a devastating malignancy with an extremely poor prognosis, as shown by the 5-years survival rate of 2-9%, ranking firmly ...

5. jnm.snmjournals.org jnm.snmjournals.org/content/62/supplement_1/1469

C-C Chemokine Receptor Type 2-Targeting Ultrasmall ... PET/CT imaging using 64Cu-CuNCs-ECL1i was measured in two genetically-engineered mouse models (GEMMs) including p48-CRE; LSL-KRasG12D/wt; p53 ...

6. reporter.nih.gov reporter.nih.gov/search/D8ieGRcSrEmrgaD69xmO6A/project-details/9668630

Novel CCR2 PET for Pancreatic Cancer ... - NIH RePORTER We hypothesize that 64Cu-DOTA-ECL1i can sensitively and specifically detect CCR2 in PDAC, track the variation following CCR2-targeted treatment, and likely ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12285706/

Targeting tumor-associated CCR2 + macrophages to inhibit ... Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with pronounced resistance to conventional therapies.