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

NCT03007719 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 16709NCI-2017-01323
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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.

Conditions

Bladder Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  Up to 2 weeks

Secondary Outcomes (2)

• 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

• 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

Study Arms (2)

Cohort 1: Neoadjuvant

EXPERIMENTAL

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.

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

Cohort 2: Standard of Care (SOC)

EXPERIMENTAL

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.

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

Interventions

Fluorine F 18 Ara-G DRUG

Given IV

Also known as: 2'-deoxy-2'-fluoro-9-β-D-arabinofuranosylguanine, VisAcT

Cohort 1: Neoadjuvant; Cohort 2: Standard of Care (SOC)

Positron Emission Tomography PROCEDURE

Undergo PET/MR imaging

Also known as: PET, PET Scan

Cohort 1: Neoadjuvant; Cohort 2: Standard of Care (SOC)

Magnetic Resonance Imaging PROCEDURE

Undergo PET/MR imaging

Also known as: MRI

Cohort 1: Neoadjuvant; Cohort 2: Standard of Care (SOC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Lawrence Fong: lead
• CellSight Technologies, Inc.: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94158, United States

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Limitations and Caveats

This study was terminated due to low accrual. Only four participants were accrued to Cohort 2 (SOC) for this protocol. No patients were enrolled for cohort 1.

Results Point of Contact

• Title: Dr. Lawrence Fong
• Organization: University of California, San Francisco

Lawrence.Fong@ucsf.edu

(415) 353-2051

Study Officials

• Lawrence Fong, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor in Residence

Study Record Dates

• First Submitted: December 28, 2016
• First Posted: January 2, 2017
• Study Start: March 7, 2017
• Primary Completion: January 11, 2019
• Study Completion: January 11, 2019
• Last Updated: January 21, 2020
• Results First Posted: January 21, 2020

Record last verified: 2020-01

Locations

US (1)