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Study to Evaluate CD8 PET Imaging as a Marker of Immune Response to Stereotactic Body Radiation Therapy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05371132
Recruitment Status : Recruiting
First Posted : May 12, 2022
Last Update Posted : June 27, 2022
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
City of Hope Medical Center

Brief Summary:
This phase I trial investigates the effect of radiation therapy on the immune system, specifically CD8 positive (+) T cells. CD8+ T cells are mainly found in lymph tissue and play a significant role in anti-tumor immunity. These cells can infiltrate tumor cells and kill them. Radiation therapy may recruit CD8 T cells and this recruitment may help with tumor control. Diagnostic procedures, such as zirconium Zr 89-Df-crefmirlimab positron emission tomography (PET), may be a less invasive way to check and monitor for CD8+ T cells before and after radiation therapy.

Condition or disease Intervention/treatment Phase
Metastatic Malignant Solid Neoplasm Procedure: Positron Emission Tomography Radiation: Stereotactic Body Radiation Therapy Drug: Zirconium Zr 89-Df-Crefmirlimab Phase 1

Detailed Description:

PRIMARY OBJECTIVE:

I. Evaluate if there is an increase in CD8+ T cells after stereotactic body radiation therapy (SBRT) in irradiated tumors.

SECONDARY OBJECTIVES:

I. To report on the time evolution of zirconium Zr 89-Df-crefmirlimab (CD8 PET tracer) uptake after infusion.

II. To compare CD8 PET tracer uptake at irradiated lesions to uptake at non-irradiated lesions (if any).

III. To assess how differences in site, histology and/or prior therapy relate to immune characterization and changes IV. To assess serum biomarkers of immune response before and after SBRT. V. To assess ability of CD8 PET tracer and imaging to be a biomarker of SBRT. VI. Evaluate CD8 PET tracer with Response Evaluation Criteria in Solid Tumors (RECIST) radiology measurements.

VII. To report any adverse events associated with 2 doses of CD8 PET tracer when used in combination with SBRT.

EXPLORATORY OBJECTIVE:

I. Blood will be collected, processed, and stored for future immune profiling or other correlatives pending additional funding.

OUTLINE:

Patients receive zirconium Zr 89-Df-crefmirlimab intravenously (IV) over 5-10 minutes and then under PET imaging 24 hours after infusion before and after SBRT. Patients undergo SBRT every 2-5 days for a total of 5 fractions.

After completion of study treatment, patients are followed up at 4-6 weeks, 3 months, 1 year, and then periodically for 2 years.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Pilot Phase I Study to Evaluate CD8 PET Imaging as a Marker of Immune Response to Stereotactic Body Radiation Therapy (ELIXR)
Estimated Study Start Date : July 15, 2022
Estimated Primary Completion Date : August 16, 2023
Estimated Study Completion Date : August 16, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Zirconium

Arm Intervention/treatment
Experimental: Basic science (zirconium Zr 89-Df-crefmirlimab, PET, SBRT)
Patients receive zirconium Zr 89-Df-crefmirlimab IV over 5-10 minutes and then under PET imaging 24 hours after infusion before and after SBRT. Patients undergo SBRT every 2-5 days for a total of 5 fractions.
Procedure: Positron Emission Tomography
Undergo PET
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • proton magnetic resonance spectroscopic imaging

Radiation: Stereotactic Body Radiation Therapy
Undergo SBRT
Other Names:
  • SABR
  • SBRT
  • Stereotactic Ablative Body Radiation Therapy

Drug: Zirconium Zr 89-Df-Crefmirlimab
Given IV
Other Names:
  • 89Zr-Crefmirlimab Berdoxam
  • 89Zr-Desferrioxamine-IAB22M2C
  • 89Zr-Df-Crefmirlimab
  • 89Zr-Df-IAB22M2C
  • Zirconium Zr 89-Df-IAB22M2C
  • ZIRCONIUM ZR-89-DESFERRIOXAMINE-IAB22M2C




Primary Outcome Measures :
  1. Change in CD8 positron emission tomography (PET) maximum standardized uptake value (SUVmax) [ Time Frame: Pre-SBRT to post-SBRT (comparison of CD8 PET SUV at day -1, and at 1 week after completion of SBRT) ]
    CD8 PET SUV will be measured as SUVmax, the maximum SUV measurement within the tumor voxels. If patients have multiple tumors treated with stereotactic body radiation therapy (SBRT), average within-tumor change will be used for that patient for the primary analysis. As a result, this primary analysis is a comparison of the change in CD8 PET SUV in 10 patients.


Secondary Outcome Measures :
  1. Time evolution of CD8 PET SUV (decay corrected) [ Time Frame: From pre-SBRT to post-SBRT (comparison of CD8 PET SUV at day -1, and at each of 5 fractions of SBRT administered 2-5 days apart, and additional imaging 1-2 weeks after completion of SBRT) ]
    CD8 PET SUVs from PET scans taken before, during and after SBRT.

  2. Site specific differences in immune characterization (CD8 PET SUV) and changes [ Time Frame: From pre-SBRT to post-SBRT ( CD8 PET SUV at day -1, and at each of 5 fractions of SBRT administered 2-5 days apart, and additional imaging 1-2 weeks after completion of SBRT). ]
    CD8 PET SUV and change in CD8 PET SUV at tumor sites will be collected to assess whether immune activity and response is different at different sites of disease (e.g., lymph node vs bone)

  3. Histology specific differences in immune characterization (CD8 PET SUV) and changes [ Time Frame: From pre-SBRT to post-SBRT ( CD8 PET SUV at day -1, and at each of 5 fractions of SBRT administered 2-5 days apart, and additional imaging 1-2 weeks after completion of SBRT). ]
    CD8 PET SUV and change in CD8 PET SUV will be collected to assess whether immune activity and response is different depending on the patient's disease type and histopathology.

  4. Evaluation of tumor response (fludeoxyglucose F-18 [FDG] PET and/or computed tomography [CT]) as it relates to both baseline CD8 PET SUV and changes observed after SBRT. [ Time Frame: Pre-SBRT to post-SBRT (1-2 weeks after completion of SBRT). Additional RECIST response assessments will be conducted per standard of care and will be assessed for up to 2 years to compare to CD8 SUVs post-SBRT and changes in CD8 SUVs. ]
    RECIST response and evaluation endpoints will be used to assess tumor response from CT imaging, and SUVmax will be used for FDG-PET imaging. Data will be compared with CD8 PET SUVs (e.g. SUVmax of CD8 PET) and changes pre- and post-SBRT. For multiple lesions irradiated SUVmax will be averaged.

  5. Incidence of adverse events [ Time Frame: From the first CD8 PET tracer infusion to 4-6 weeks after the last CD8 PET tracer infusion. ]
    Number and type of adverse events related to the study treatment


Other Outcome Measures:
  1. Correlation between immune characterization of blood samples and CD8 PET SUVs and tumor response [ Time Frame: Pre-SBRT to post-SBRT (1 week after completion of SBRT) ]
    Changes in circulating levels of immune cells and cytokines will be compared to changes in CD8 PET SUVs and tumor response (measured by RECIST or FDG PET SUVs). If multiple lesions, the average will be used. Most metrics will use SUVmax, although others will be explored.



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:

  • Documented informed consent of the participant and/or legally authorized representative
  • Participant is willing and able to comply with all protocol required procedures
  • Age: >= 18 years
  • Eastern Cooperative Oncology Group (ECOG) =< 2
  • Metastatic patients of any solid tumor malignancy amenable for SBRT as determined by the radiation oncologist
  • Lymphoma patients may be allowed as determined by the principal investigator (PI)
  • No change in systemic treatment regimen for past 2 months prior to start of SBRT
  • Patients able to comply with daily PET after SBRT
  • Patient meets all clinical safety lab values per institution's standard of care, or Investigator's discretion, for patients receiving cancer treatment
  • Women of childbearing potential (WOCBP): negative urine or serum pregnancy test

    • If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Agreement by females and males of childbearing potential to use effective double barrier contraceptive methods or abstain from heterosexual activity for the course of the study through at least 30 days after the last administration of the CD8 PET tracer

    • Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)

Exclusion Criteria:

  • Patient who have splenic disorders or had splenectomy that per PI would interfere with CD8 imaging
  • Patients should not have any uncontrolled illness including ongoing or active infection
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to CD8 PET tracer
  • Serious nonmalignant disease or conditions that could compromise protocol objectives, in the opinion of the investigator
  • Females only: Pregnant or breastfeeding

    • Pregnant women are excluded from this study because CD8 PET tracer is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with CD8 PET tracer, breastfeeding should be discontinued if the mother is treated with CD8 PET tracer
  • Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
  • Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

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): NCT05371132


Locations
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United States, California
City of Hope Medical Center Recruiting
Duarte, California, United States, 91010
Contact: Savita V. Dandapani    626-359-8111    sdandapani@coh.org   
Principal Investigator: Savita V. Dandapani         
Sponsors and Collaborators
City of Hope Medical Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Savita V Dandapani City of Hope Medical Center
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Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT05371132    
Other Study ID Numbers: 21221
NCI-2022-02037 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
21221 ( Other Identifier: City of Hope Medical Center )
P30CA033572 ( U.S. NIH Grant/Contract )
First Posted: May 12, 2022    Key Record Dates
Last Update Posted: June 27, 2022
Last Verified: June 2022

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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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Deferoxamine
Siderophores
Iron Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action