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

Phase 2

Terminated

Conditions: Bladder Cancer

Interventions: Drug: Fluorine F 18 Ara-G
Procedure: Positron Emission Tomography
Procedure: Magnetic Resonance Imaging

Registration Number: NCT03007719

Lead Sponsor: Lawrence Fong

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 4

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 2: Standard of Care (SOC)	Magnetic Resonance Imaging	Patients with any cancer type who are planned to initiate standard of care (SOC) anti-PD-1 or anti-PD-L1 treatment (Cohort 2). For the SOC cohort, study participants will undergo whole body PET/MR imaging with \[18F\]F-AraG within 7 days of initiating Cycle 1 anti-PD-1 or anti-PD-L1, and between Cycle 1 Day 15 (C1D15) and Cycle 2 Day 7 (C2D7) anti-PD-1 or anti-PD-L1. Approximately 19 patients will be enrolled.
Cohort 1: Neoadjuvant	Positron Emission Tomography	Patients with localized bladder cancer who are eligible for the UCSF phase 2 clinical trial of neoadjuvant atezolizumab before definitive surgery (NCT02451423) (Cohort 1). For the neoadjuvant cohort, study participants will undergo whole body PET/MR imaging with \[18F\]F-AraG within 7 days of initiating atezolizumab and within 7 days before surgery. Approximately 12 patients will be enrolled.
Cohort 1: Neoadjuvant	Magnetic Resonance Imaging	Patients with localized bladder cancer who are eligible for the UCSF phase 2 clinical trial of neoadjuvant atezolizumab before definitive surgery (NCT02451423) (Cohort 1). For the neoadjuvant cohort, study participants will undergo whole body PET/MR imaging with \[18F\]F-AraG within 7 days of initiating atezolizumab and within 7 days before surgery. Approximately 12 patients will be enrolled.
Cohort 1: Neoadjuvant	Fluorine F 18 Ara-G	Patients with localized bladder cancer who are eligible for the UCSF phase 2 clinical trial of neoadjuvant atezolizumab before definitive surgery (NCT02451423) (Cohort 1). For the neoadjuvant cohort, study participants will undergo whole body PET/MR imaging with \[18F\]F-AraG within 7 days of initiating atezolizumab and within 7 days before surgery. Approximately 12 patients will be enrolled.
Cohort 2: Standard of Care (SOC)	Fluorine F 18 Ara-G	Patients with any cancer type who are planned to initiate standard of care (SOC) anti-PD-1 or anti-PD-L1 treatment (Cohort 2). For the SOC cohort, study participants will undergo whole body PET/MR imaging with \[18F\]F-AraG within 7 days of initiating Cycle 1 anti-PD-1 or anti-PD-L1, and between Cycle 1 Day 15 (C1D15) and Cycle 2 Day 7 (C2D7) anti-PD-1 or anti-PD-L1. Approximately 19 patients will be enrolled.
Cohort 2: Standard of Care (SOC)	Positron Emission Tomography	Patients with any cancer type who are planned to initiate standard of care (SOC) anti-PD-1 or anti-PD-L1 treatment (Cohort 2). For the SOC cohort, study participants will undergo whole body PET/MR imaging with \[18F\]F-AraG within 7 days of initiating Cycle 1 anti-PD-1 or anti-PD-L1, and between Cycle 1 Day 15 (C1D15) and Cycle 2 Day 7 (C2D7) anti-PD-1 or anti-PD-L1. Approximately 19 patients will be enrolled.

Primary Outcome Measures

Name	Time	Method
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.	Up to 2 weeks	The nonparametric paired Wilcoxon Signed-rank test will be used to assess differences in SUVmax before and after treatment. The log2 ratio of post-treatment versus baseline SUVmax within the tumor and lymphoid tissues will also be calculated

Secondary Outcome Measures

Name	Time	Method
Change Between Pre-treatment and Post-treatment SUVmax in Lymphoid Organs on Whole-body [18F]F-AraG PET/MR Imaging (Cohort 1 and 2)	Up to 8 days
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)	Up to 6 weeks	To correlate change in SUVmax to clinical and/or pathologic response, patients will be divided into two groups: those who achieved clinical response and/or pathologic downs-staging, and those who did not. The median and interquartile range of change in SUVmax from baseline to pre-surgery in the different groups will be descriptively reported. For Cohort 1, clinical response will be determined by abdominal imaging performed \<30 days after the last dose of atezolizumab prior to cystectomy compared to baseline pre-treatment imaging using RECIST v1.1 criteria, as specified in the companion treatment protocol. For Cohort 1, pathologic response will be determined by evidence of down-staging (e.g. from muscle invasive to non-muscle invasive, or complete pathologic response) at the time of cystectomy.