64Cu-DOTA-ECL1i PET/CT in Predicting Tumor Expression of CCR2 in Patients with Pancreatic Cancer
This phase I trial studies whether 64Cu-DOTA-ECL1i positron emission tomography (PET)/computed tomography (CT) can detect CCR2 expression in patients with pancreatic cancer. Comparing results of diagnostic procedures, such as 64Cu-DOTA-ECL1i PET/CT done before and after chemotherapy or surgery may help doctors predict a patient's response to treatment and help plan the best treatment.
Inclusion Criteria
- Adult patients 18 years of age or older with: * Newly diagnosed early-staged localized 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 any 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], principle investigator [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 magnetic resonance imaging [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.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03851237.
PRIMARY OBJECTIVES:
I. To evaluate whether tumor uptake of copper Cu 64-tetraxetan (DOTA)-ECL1i (64Cu-DOTA-ECL1i) correlates with tumor expression of CCR2 and response to surgery or chemotherapy in pancreatic ductal adenocarcinoma (PDAC) patients.
Ia. To determine whether 64Cu-DOTA-ECL1i can detect CCR2 expression in PDAC tumors in patients at any of the following time points: prior to the start of any chemotherapy or a change in chemotherapy, pre-surgery without intervention or pre-surgery with intervention.
Ib. To 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 in patients with newly diagnosed locally advanced, borderline resectable or metastatic PDAC.
II. To evaluate whether tumor uptake of 64Cu-DOTA-ECL1i predicts response to CCR2-directed therapy in PDAC patients treated with CCR2/5i and chemo-immunotherapy (Close to Accrual - March 2022).
IIa. To evaluate whether tumor uptake of 64Cu-DOTA-ECL1i posttherapy correlates with CCR2 expression and is predictive of response to CCR2-directed therapy.
IIb. To evaluate whether the change in tumor uptake of 64Cu-DOTA-ECL1i is predictive of response to CCR2-directed therapy newly diagnosed locally advanced, borderline resectable PDAC.
IIc. To correlate changes in tumor uptake of 64Cu-DOTA-ECL1i with changes in CCR2 expression in monocytes in the paired tumor biopsies and peripheral blood samples using flow cytometry following therapy. (Exploratory Aim)
OUTLINE: Patients are assigned to 1 of 3 cohorts.
COHORT Ia: Patients with newly diagnosed early-staged localized PDAC receive copper Cu 64-DOTA-ECL1i intravenously (IV) and undergo copper Cu 64-DOTA-ECL1i PET/CT over 60 minutes before undergoing Whipple procedure of the pancreas. Patients also undergo collection of blood samples at baseline.
COHORT Ib: Patients with borderline resectable, locally advanced, metastatic, or recurrent PDAC receive copper Cu 64-DOTA-ECL1i IV and undergo copper Cu 64-DOTA-ECL1i PET/CT over 60 minutes before initiation of standard chemotherapy. Patients who experience disease progression after 2-4 months of chemotherapy, undergo a second copper Cu 64-DOTA-ECL1i PET/CT scan. Patients also undergo collection of blood samples at baseline.
COHORT II: Patients receive copper Cu 64-DOTA-ECL1i and undergo copper Cu 64-DOTA-ECL1i PET/CT over 60 minutes before initiation of CCR2 targeted therapy and after 2 cycles of CCR2 targeted therapy. Patients also undergo collection of blood samples at baseline.
After completion of study treatment, patients are followed up at 24 hours and at 2-6 months after study entry.
Trial PhasePhase I
Trial Typediagnostic
Lead OrganizationSiteman Cancer Center at Washington University
Principal InvestigatorFarrokh Dehdashti
- Primary ID201807099
- Secondary IDsNCI-2019-02280
- ClinicalTrials.gov IDNCT03851237