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

• Sponsor: Lawrence Fong (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03007719
• Collaborator: CellSight Technologies, Inc. (Industry)
• Enrollment: 4
• Location: 1
• Arms: 2
• Actual Duration (Months): 22.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Bladder Cancer	Drug: Fluorine F 18 Ara-G; Procedure: Positron Emission Tomography; Procedure: Magnetic Resonance Imaging	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. 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:

1. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• 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
• Actual Study Start Date: Mar 7, 2017
• Actual Primary Completion Date: Jan 11, 2019
• Actual Study Completion Date: Jan 11, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1: Neoadjuvant 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; Given IV; Other Names: 2'-deoxy-2'-fluoro-9-β-D-arabinofuranosylguanine VisAcT ; Procedure: Positron Emission Tomography; Undergo PET/MR imaging; Other Names: PET PET Scan ; Procedure: Magnetic Resonance Imaging; Undergo PET/MR imaging; Other Names: MRI
Experimental: Cohort 2: Standard of Care (SOC) 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; Given IV; Other Names: 2'-deoxy-2'-fluoro-9-β-D-arabinofuranosylguanine VisAcT ; Procedure: Positron Emission Tomography; Undergo PET/MR imaging; Other Names: PET PET Scan ; Procedure: Magnetic Resonance Imaging; Undergo PET/MR imaging; Other Names: MRI

Outcome Measures

Primary Outcome Measures

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. [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

1. 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.

2. 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]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, San Francisco	San Francisco	California	United States	94158

Sponsors and Collaborators

• Lawrence Fong
• CellSight Technologies, Inc.

Investigators

• Principal Investigator: Lawrence Fong, MD, University of California, San Francisco

Study Documents (Full-Text)

• Informed Consent Form - Nov 13, 2018
• Study Protocol and Statistical Analysis Plan - Feb 20, 2018

More Information

Publications

None provided.

• Responsible Party: Lawrence Fong, Professor in Residence, University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT03007719
• Other Study ID Numbers: 16709; NCI-2017-01323
• First Posted: Jan 2, 2017
• Last Update Posted: Jan 21, 2020
• Last Verified: Jan 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Carcinoma, Transitional Cell; Fluorides

Study Results

Participant Flow

Recruitment Details	This study was closed due to low accrual. Only 4 patients were enrolled to this protocol and all were assigned to cohort 2

Arm/Group Title	Cohort 1: Neoadjuvant	Cohort 2: Standard of Care (SOC)
Arm/Group Description	Patients with localized bladder cancer who are eligible for the University of California, San Francisco (UCSF) phase 2 clinical trial of neoadjuvant atezolizumab before definitive surgery (NCT02451423) (Cohort 1).	Patients with any cancer type who are planned to initiate standard of care (SOC) anti-PD-1 or anti-PD-L1 treatment (Cohort 2).
Period Title: Overall Study
STARTED	0	4
COMPLETED	0	4
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Cohort 1: Neoadjuvant	Cohort 2: Standard of Care (SOC)	Total
Arm/Group Description	Patients with localized bladder cancer who are eligible for the University of California, San Francisco (UCSF) phase 2 clinical trial of neoadjuvant atezolizumab before definitive surgery (NCT02451423) (Cohort 1).	Patients with any cancer type who are planned to initiate standard of care (SOC) anti-PD-1 or anti-PD-L1 treatment (Cohort 2).	Total of all reporting groups
Overall Participants	0	4	4
Age, Customized (Count of Participants)
60-69	1 Infinity	1 25%
70-79	2 Infinity	2 50%
80-89	1 Infinity	1 25%
Sex: Female, Male (Count of Participants)
Female	0 NaN	3 75%	3 75%
Male	0 NaN	1 25%	1 25%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 NaN	1 25%	1 25%
Not Hispanic or Latino	0 NaN	3 75%	3 75%
Unknown or Not Reported	0 NaN	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 NaN	0 0%	0 0%
Asian	0 NaN	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 NaN	0 0%	0 0%
Black or African American	0 NaN	0 0%	0 0%
White	0 NaN	3 75%	3 75%
More than one race	0 NaN	0 0%	0 0%
Unknown or Not Reported	0 NaN	1 25%	1 25%
Region of Enrollment (participants) [Number]
United States	4 Infinity	4 100%

Outcome Measures

1. Primary Outcome

Title	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.
Description	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
Time Frame	Up to 2 weeks

Outcome Measure Data

Analysis Population Description

SUVmax data not collected

Arm/Group Title	Cohort 1: Neoadjuvant	Cohort 2: Standard of Care (SOC)
Arm/Group Description	Patients with localized bladder cancer who are eligible for the University of California, San Francisco (UCSF) phase 2 clinical trial of neoadjuvant atezolizumab before definitive surgery (NCT02451423) (Cohort 1).	Patients with any cancer type who are planned to initiate standard of care (SOC) anti-PD-1 or anti-PD-L1 treatment (Cohort 2).
Measure Participants	0	0

2. Secondary Outcome

Title	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)
Description	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.
Time Frame	Up to 6 weeks

Outcome Measure Data

Analysis Population Description

SUVmax data not collected

Arm/Group Title	Cohort 1: Neoadjuvant
Arm/Group Description	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. Fluorine F 18 Ara-G: Given IV Positron Emission Tomography: Undergo PET/MR imaging Magnetic Resonance Imaging: Undergo PET/MR imaging
Measure Participants	0

3. Secondary Outcome

Title	Change Between Pre-treatment and Post-treatment SUVmax in Lymphoid Organs on Whole-body [18F]F-AraG PET/MR Imaging (Cohort 1 and 2)
Time Frame	Up to 8 days

Outcome Measure Data

Analysis Population Description

SUVmax data not collected

Arm/Group Title	Cohort 1: Neoadjuvant	Cohort 2: Standard of Care (SOC)
Arm/Group Description	Patients with localized bladder cancer who are eligible for the University of California, San Francisco (UCSF) phase 2 clinical trial of neoadjuvant atezolizumab before definitive surgery (NCT02451423) (Cohort 1).	Patients with any cancer type who are planned to initiate standard of care (SOC) anti-PD-1 or anti-PD-L1 treatment (Cohort 2).
Measure Participants	0	0

Adverse Events

Time Frame	Patients were evaluated one day and one week via telephone visit after each radiopharmaceutical injection for safety follow-up, up to 6 weeks.
Adverse Event Reporting Description	No patients were enrolled in Cohort 1. All patients who receive any dose of [18F]F-AraG were analyzed for safety, all adverse events were recorded. Patients removed from study for unacceptable treatment related adverse event(s) were followed until resolution or stabilization of all treatment related adverse events (AE) to Grade 0-1.
Arm/Group Title	Cohort 2: Standard of Care (SOC)
Arm/Group Description	Patients with any cancer type who are planned to initiate standard of care (SOC) anti-PD-1 or anti-PD-L1 treatment.
All Cause Mortality
	Cohort 2: Standard of Care (SOC)
	Affected / at Risk (%)	# Events
Total	1/4 (25%)
Serious Adverse Events
	Cohort 2: Standard of Care (SOC)
	Affected / at Risk (%)	# Events
Total	1/4 (25%)
Renal and urinary disorders
Hematuria	1/4 (25%)	1
Other (Not Including Serious) Adverse Events
	Cohort 2: Standard of Care (SOC)
	Affected / at Risk (%)	# Events
Total	0/4 (0%)

Limitations/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.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.