Clinical trial NCT03851237: CCR2 PET for Pancreatic Cancer Imaging and Prediction of Response to Standard and CCR2-Targeted Therapy
Official title: Novel CCR2 PET for Pancreatic Cancer Imaging and Prediction of Response to Standard and CCR2-Targeted Therapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Pancreatic Ductal Adenocarcinoma
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2019-02-22
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: 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
measure: 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
timeFrame: Completion of first scan (day 1)
measure: 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
timeFrame: Baseline and after 2 cycles of CCR directed therapy (estimated to be 2 months)
measure: 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
timeFrame: Baseline and after 2 cycles of CCR2 directed therapy (estimated to be 2 months)
Secondary outcomes:
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Farrokh Dehdashti, M.D.
role: PRINCIPAL_INVESTIGATOR
References: