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

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ClinicalTrials.gov Identifier: NCT03851237
Recruitment Status : Recruiting
First Posted : February 22, 2019
Last Update Posted : February 22, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Washington University School of Medicine

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.


Condition or disease Intervention/treatment Phase
Pancreatic Ductal Adenocarcinoma Drug: 64Cu-DOTA-ECLIi Device: CTI/Siemens Biography 40 PET/CT Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Novel CCR2 PET for Pancreatic Cancer Imaging and Prediction of Response to Standard and CCR2-Targeted Therapy
Actual Study Start Date : January 2, 2019
Estimated Primary Completion Date : May 31, 2025
Estimated Study Completion Date : May 31, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cohort 1a: Standard of Care Whipple Treatment
  • Standard of care diagnostic biopsy
  • 64Cu-DOTA-ECL1i-PET/CT imaging - immediately after the dynamic study
  • Standard of care Whipple procedure
Drug: 64Cu-DOTA-ECLIi
-The first five patients enrolled on study will undergo an additional delayed imaging time point approximately 2-6 hours following 64Cu-DOTA-ECL1i

Device: CTI/Siemens Biography 40 PET/CT
-Standard of care

Experimental: Cohort 1b: Standard of Care Treatment Chemotherapy
  • Standard of care diagnostic biopsy (tissue to be used for CCR2 expression)
  • 64Cu-DOTA-ECL1i-PET/CT imaging pretherapy
  • 2-3 cycles of standard of care (SOC) chemotherapy
  • Additional 64Cu-DOTA-ECL1i-PET/CT imaging for patients with metastatic disease who progressed on SOC chemotherapy
Drug: 64Cu-DOTA-ECLIi
-The first five patients enrolled on study will undergo an additional delayed imaging time point approximately 2-6 hours following 64Cu-DOTA-ECL1i

Device: CTI/Siemens Biography 40 PET/CT
-Standard of care

Experimental: Cohort 2: CCR2-Targeted Therapy
  • Biopsy per therapeutic protocol (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
-The first five patients enrolled on study will undergo an additional delayed imaging time point approximately 2-6 hours following 64Cu-DOTA-ECL1i

Device: CTI/Siemens Biography 40 PET/CT
-Standard of care




Primary Outcome Measures :
  1. 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 [ Time Frame: Completion of first scan (day 1) ]
    • 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

  2. Cohort 1b only: Evaluate whether tumor uptake of 64Cu-DOTA-ECL1i prior to therapy predicts response to standard of care chemotherapy as measured by tumor SUVmax [ Time Frame: Completion of first scan (day 1) ]
    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.

  3. 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 [ Time Frame: Baseline and after 2 cycles of CCR directed therapy (estimated to be 2 months) ]
    • 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.

  4. 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 [ Time Frame: Baseline and after 2 cycles of CCR2 directed therapy (estimated to be 2 months) ]
    • 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult patients 18 years of age or older with newly diagnosed early-staged localized pancreatic ductal adenocarcinoma (PDAC) (cohort 1a), borderline resectable, locally advanced, or metastatic PDAC (cohort 1b) or borderline resectable, locally advanced (cohort 2) with 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]
  • Must be eligible to undergo Whipple procedure (cohort 1a) and/or standard chemotherapy including FLFIRINOX or gemcitabine/nab-paclitaxel (Cohort 1b) OR eligible 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] (Cohort 2)
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03851237


Contacts
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Contact: Farrokh Dehdashti, M.D. 314-362-1474 dehdashtif@wustl.edu

Locations
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United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Farrokh Dehdashti, M.D.    314-362-1474    dehdashtif@wustl.edu   
Principal Investigator: Farrokh Dehdashti, M.D.         
Sub-Investigator: Kian-Huat Lim, M.D., Ph.D.         
Sub-Investigator: Yongjian Liu, Ph.D.         
Sub-Investigator: Marianna Ruzinova, M.D., Ph.D.         
Sub-Investigator: Richard Laforest, Ph.D.         
Sub-Investigator: William Hawkins, M.D.         
Sub-Investigator: Amber Salter, Ph.D.         
Sponsors and Collaborators
Washington University School of Medicine
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Farrokh Dehdashti, M.D. Washington University School of Medicine

Additional Information:
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Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT03851237     History of Changes
Other Study ID Numbers: 201807099
1R01CA235672-01 ( U.S. NIH Grant/Contract )
First Posted: February 22, 2019    Key Record Dates
Last Update Posted: February 22, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms