Clinical trial NCT03007719: Functional Imaging of T-Cell Activation With [18F]F-AraG in Urothelial Carcinoma Patients Receiving Neoadjuvant Therapy or Patients With Cancer Receiving Standard of Care Anti-PD-1/L1
Official title: Functional Imaging of T-Cell Activation With [18F]F-AraG in Urothelial Carcinoma Patients Receiving Neoadjuvant Therapy or Patients With Cancer Receiving Standard of Care Anti-PD-1/L1
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Bladder Cancer
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: CellSight Technologies, Inc.
First posted: 2017-01-02
Enrollment: 4
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: This phase II trial studies how well fluorine F 18 Ara-G positron emission tomography (PET)/magnetic resonance (MR) imaging works in measuring clinical response to atezolizumab or patients with cancer receiving standard of care Anti-PD-1/L1. Diagnostic procedures, such as fluorine F 18 Ara-G PET/MR imaging, may help measure a patient's response to standard of care atezolizumab or Anti-PD-1/L1 treatment.

Detailed description: PRIMARY OBJECTIVES:

I. To assess the change in fluorine F 18 Ara-G (\[18F\]F-AraG) uptake in primary and/or metastatic tumor(s) on whole-body \[18F\]F-AraG PET/MR imaging associated with neoadjuvant atezolizumab and standard of care (SOC) anti-PD-1 or anti-PD-L1 treatment.

SECONDARY OBJECTIVES:

I. To correlate change in \[18F\]F-AraG uptake within the primary tumor with clinical and pathologic response in patients treated with neoadjuvant atezolizumab. (Cohort 1) II. To assess \[18F\]F-AraG uptake in lymphoid organs before and after anti-PD-1 or anti-PD-L1 treatment. (Cohort 1 and 2)

OUTLINE: Patients are assigned to 1 or 2 cohorts.

COHORT I (NEOADJUVANT COHORT): Patients receive fluorine F 18 Ara-G intravenously (IV) and undergo PET/MR imaging over 1.5-3 hours within 7 days of starting standard of care atezolizumab and within 7 days before surgery.

COHORT II (SOC COHORT): Patients receive fluorine F 18 Ara-G IV and undergo PET/MR imaging over 1.5-3 hours within 7 days of initiating course 1 of anti-PD-1 or anti-PD-L1 therapy and between day 15 of course 1 and day 7 of course 2 of anti-PD-1 or anti-PD-L1 treatment.

After completion of study, patients are followed up at days 2 and 8.

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically documented cancer to which anti-PD1 or anti-PDL1 are approved therapies
* Eligible for with plan to undergo neoadjuvant treatment with atezolizumab followed by surgery as part of a companion study (NCT02451423), or planned to undergo treatment with anti-PD-1 or anti-PD-L1 per standard of care
* Must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 regardless of disease stage (e.g. localized, locally advanced, or metastatic)
* In female patients, negative pregnancy test with no plans to become pregnant during the duration of the study
* Able to provide informed consent and follow the study guidelines
* Archival tumor tissue from biopsy or resection will be required for all patients; archival tissue should be of good quality based on total and viable tumor contents; fine needle aspiration, brushing, and cytologic cell pellets are not acceptable

Exclusion Criteria:

* History of prior treatment with immune checkpoint antibodies (e.g. anti-PD1, anti-PDL1, anti-CTLA4 antibody) or co-stimulatory agonist antibodies (e.g. anti-41BB, anti-OX40)

  \* Prior intravesical treatment with Bacillus Calmette-Guerin (BCG) is allowed; however, the last dose must be at least 6 weeks from time of enrollment and patients must have documented progressive disease at least 6 weeks from completion of last BCG
* Diagnosis of immunodeficiency including history of human immunodeficiency virus (HIV)
* Receiving systemic steroid therapy or any form of immunosuppressive therapy within 7 days prior to first injection of \[18F\]F-AraG

  \* Topical and inhaled corticosteroids are allowed
* Prior allogeneic stem cell or solid organ transplant
* Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
* Biopsy or resection of the primary tumor within 14 days the first injection of \[18F\]F-AraG
* Contraindication to magnetic resonance (MRI) imaging, as determined through review of the University of California, San Francisco (UCSF) MRI screening form by study investigator
* Evidence of active infection within 14 days of study enrollment
* Female patients who are pregnant or breastfeeding
* Inability to receive furosemide (Lasix) in the opinion of the treating investigator
* Patients that plan to receive off-label use of anti-PD1 or anti-PDL1

Primary outcomes:
measure: Change Between Pre-treatment and Post-treatment SUVmax (Standardized Uptake Values) in the Primary and/or Metastatic Tumor(s) on Whole-body [18F]F-AraG Positron Emission Tomography/Magnetic Resonance (PET/MR) Imaging by Study Cohort.
timeFrame: Up to 2 weeks
Secondary outcomes:
measure: Compare Change in SUVmax of the Primary Tumor in Patients Who Achieve Pathologic Downstaging or Clinical Response and Those Without Pathologic or Clinical Response at Time of Surgery in Patients Receiving Neoadjuvant Atezolizumab (Cohort 1)
timeFrame: Up to 6 weeks
measure: Change Between Pre-treatment and Post-treatment SUVmax in Lymphoid Organs on Whole-body [18F]F-AraG PET/MR Imaging (Cohort 1 and 2)
timeFrame: Up to 8 days
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
Study officials:
affiliation: University of California, San Francisco
name: Lawrence Fong, MD
role: PRINCIPAL_INVESTIGATOR
References: