CCR2 PET for Pancreatic Cancer Imaging and Prediction of Response to Standard and CCR2-Targeted Therapy

Study Overview
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Brief Summary
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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.

Official Title
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Novel CCR2 PET for Pancreatic Cancer Imaging and Prediction of Response to Standard and CCR2-Targeted Therapy

Conditions
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Pancreatic Ductal Adenocarcinoma

Intervention / Treatment
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* Drug: 64Cu-DOTA-ECLIi
* Device: PET/CT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients 18 years of age or older with: newly diagnosed early-staged localized pancreatic ductal adenocarcinoma (PDAC) scheduled to undergo Whipple procedure (cohort 1a) or down-staged after neoadjuvant chemotherapy now eligible to undergo resection OR borderline resectable, locally advanced, metastatic, or recurrent PDAC (cohort 1b) scheduled to undergo chemotherapy OR borderline resectable, locally advanced PDAC (cohort 2) who is eligible and / or signed consent to undergo CCR2-targeted therapy example:[(phase 1/2 clinical trial combining an oral CCR2/5i (BMS-813160) with chemotherapy (gemcitabine plus nab-paclitaxel) and anti-PD-1 (nivolumab), PI, Dr. Kian Lim) HRPO #201806007 - closed to accrual March 2022] AND at least one measurable [defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan or MRI] A cohort 1B subject who has been previously treated for PDAC with a diagnosis of recurrence and a lesion size of 1.5 cm or greater will be allowed to enroll before institution of therapy or within 20 days after starting a 2nd line or later (new therapy) for recurrent disease. Able to give informed consent Not currently pregnant or nursing: Subject must be surgically sterile (has had a documented bilateral oophorectomy and/or documented hysterectomy), post-menopausal (cessation of menses for more than 1 year), non-lactating, or of childbearing potential for whom a urine pregnancy test (with the test performed within the 24 hour period immediately prior to administration of 64Cu-DOTA-ECL1i) is negative Exclusion Criteria: Patients with other invasive malignancies, with the exception of non-melanoma skin cancer, who had (or have) any evidence of the other cancer present within the last 5 years Unable to tolerate up to 90 min of PET/CT imaging per imaging session.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1a: Treatment Whipple/Surgical Procedure/Surgery following neoadjuvant therapy<br>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. | Drug: 64Cu-DOTA-ECLIi<br>* -The first four patients enrolled on study will undergo an additional delayed imaging time point approximately 2-6 hours following 64Cu-DOTA-ECL1i<br>Device: PET/CT<br>* -Standard of care<br>|
| Experimental: Cohort 1b: Standard of Care Treatment Chemotherapy<br>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 | Drug: 64Cu-DOTA-ECLIi<br>* -The first four patients enrolled on study will undergo an additional delayed imaging time point approximately 2-6 hours following 64Cu-DOTA-ECL1i<br>Device: PET/CT<br>* -Standard of care<br>|
| Experimental: Cohort 2: CCR2-Targeted Therapy<br>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 | Drug: 64Cu-DOTA-ECLIi<br>* -The first four patients enrolled on study will undergo an additional delayed imaging time point approximately 2-6 hours following 64Cu-DOTA-ECL1i<br>Device: PET/CT<br>* -Standard of care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine whether 64Cu-DOTA-ECL1i detects CCR2 expression in PDAC tumors as measured by direct comparison of visual tumor uptake on 64Cu-DOTA-ECL1i images to CCR2 measurements in surgical specimens | Visual tumor uptake as compared to background blood/tissue uptake: 1=no uptake, 2=mild uptake, 3=moderate uptake, and 5=striking update Will utilize published methods of immunohistochemical staining techniques | At any of the following time points: prior to the start of any chemotherapy or change in chemotherapy, pre-surgery without intervention or pre-surgery with intervenion | 
| Evaluate whether tumor uptake of 64Cu-DOTA-ECL1i prior to therapy (systemic therapy or surgery) or following neoadjuvant therapy prior to surgery predicts response to standard of care chemotherapy as measured by tumor SUVmax | SUVmax is a mathematical measurement of tumor burden seen on images and calculated by the following equation SUVmax= r / (a'/w) where r= radioactivity concentration in tumor (kBq/ml) as measured by the PET scanner within a defined region of interest, a'=the decay corrected amount of injected 64Cu-DOTA-ECL1i and w= weight of the patient in grams When PET imaging shows uptake of 64Cu-DOTA-ECL1i in site(s) of known tumor the SUVmax will be compared to clinical measurement of response to treatment taking into consideration standard response criteria including radiological imaging, laboratory values, physical examination and repeat pathology as applicable. | Completion of first scan (day 1) | 
| Evaluate whether tumor take of 64Cu-DOTA-ECL1i post therapy correlates with CCR2 expression and is predictive of response to therapy as measured by visual tumor uptake on 64Cu-DOTA-ECL1i images | Visual tumor uptake as compared to background blood/tissue uptake: 1=no uptake, 2=mild uptake, 3=moderate uptake, and 5=striking update A decrease in visual tumor uptake from baseline to post therapy imaging in cohort 2 subject is hypothesized to represent response to CCR2 directed therapy while an increase in tumor uptake is expected in cohort 1b subjects who progress while receiving standard therapy. | Baseline and after 2 cycles of CCR directed therapy (estimated to be 2 months) | 
| Evaluate if tumor take of 64Cu-DOTA-ECL1i is predictive of response to CCR2-directed therapy measured by comparison of SUVmax at imaging prior to the start of CCR2 directed therapy and SUVmax at imaging performed after 2 cycles of CCR2 directed therapy | Cohort 2 only SUVmax is a mathematical measurement of tumor burden seen on images and calculated by the following equation SUVmax= r / (a'/w) where r= radioactivity concentration in tumor (kBq/ml) as measured by the PET scanner within a defined region of interest, a'=the decay corrected amount of injected 64Cu-DOTA-ECL1i and w= weight of the patient in grams When PET imaging shows uptake of 64Cu-DOTA-ECL1i in site(s) of known tumor the SUVmax will be evaluated for change at baseline and after 2 cycles of CCR2 directed therapy. SUVmax measurements will also be compared to clinical measurement of response to treatment taking into consideration standard response criteria including radiological imaging, laboratory values, physical examination and repeat pathology as applicable | Baseline and after 2 cycles of CCR2 directed therapy (estimated to be 2 months) |