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

The Washington University

Status and phase: Completed; Phase 1

Conditions: Pancreatic Ductal Adenocarcinoma

Treatments: Device: PET/CT; Drug: 64Cu-DOTA-ECLIi

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03851237

201807099

1R01CA235672-01 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Enrollment: 69 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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69 participants in 3 patient groups

Cohort 1a: Treatment Whipple/Surgical Procedure/Surgery following neoadjuvant therapy

Experimental group

Description:

* 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.

Cohort 1b: Standard of Care Treatment Chemotherapy

Experimental group

Description:

* 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

Treatment:

Drug: 64Cu-DOTA-ECLIi

Device: PET/CT

Cohort 2: CCR2-Targeted Therapy

Experimental group

Description:

* 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

Treatment:

Drug: 64Cu-DOTA-ECLIi

Device: PET/CT