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[18F]F-AraG Imaging in Bladder Cancer Patients + Atezolizumab

This study is currently recruiting participants.
Verified July 2017 by Lawrence Fong, University of California, San Francisco
Sponsor:
ClinicalTrials.gov Identifier:
NCT03007719
First Posted: January 2, 2017
Last Update Posted: July 19, 2017
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.
Collaborator:
CellSight Technologies, Inc.
Information provided by (Responsible Party):
Lawrence Fong, University of California, San Francisco
  Purpose
This is a single-center cross-sectional imaging study in patients with localized bladder cancer undergoing neoadjuvant atezolizumab as part of a companion clinical trial (NCT02451423; Phase 2 study of atezolizumab in non-metastatic bladder transitional cell carcinoma), and patients with locally advanced or metastatic bladder cancer receiving standard of care (SOC) atezolizumab. For the neoadjuvant cohort, study participants will undergo whole body PET(Positron Emission Tomography)/MR(Magnetic Resonance) imaging with [18F]F-AraG within 7 days of initiating atezolizumab and within 7 days before surgery. For the SOC cohort, study participants will undergo whole body PET/MR imaging with [18F]F-AraG within 7 days of initiating atezolizumab and between Day 14 and Day 21 of Cycle 1 atezolizumab.

Condition Intervention Phase
Bladder Cancer Drug: [18F]F-AraG (Cohort 1) Radiation: PET/MRI Scan (Cohort 1) Drug: [18F]F-AraG (Cohort 2) Radiation: PET/MRI Scan (Cohort 2) Drug: Atezolizumab (Cohort 1) Drug: Atezolizumab (Cohort 2) Phase 2

Study Type: Interventional
Study Design: 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 Bladder Cancer Patients Receiving Neoadjuvant or Standard of Care Atezolizumab

Resource links provided by NLM:


Further study details as provided by Lawrence Fong, University of California, San Francisco:

Primary Outcome Measures:
  • The 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 PET/MR (Positron Emission Tomography/Magnetic Resonance) imaging. [ Time Frame: Baseline (within 7 days of Cycle 1 Day 1 atezolizumab; Cohort 1 and 2) to within either 7 days before surgery (after 1-3 x 3 week cycles of atezolizumab) (Cohort 1) or C1D14 (Cycle 1 Day 14) and C1D21 (Cycle 1 Day 21) atezolizumab (Cohort 2). ]
    The 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 PET/MR (Positron Emission Tomography/Magnetic Resonance) imaging by study cohort.


Secondary Outcome Measures:
  • The change in SUVmax of the primary tumor in patients who achieve pathologic down-staging or clinical response, and those without pathologic or clinical response at time of surgery in patients receiving neoadjuvant atezolizumab (Cohort 1). [ Time Frame: Baseline (within 7 days of Cycle 1 Day 1 atezolizumab) to within 7 days before surgery (after 1-3 x 3 week cycles of atezolizumab) ]
    The change in SUVmax of the primary tumor in patients who achieve pathologic down-staging (e.g. complete pathologic response) or clinical response (measured by RECIST (Response Evaluation Criteria In Solid Tumors) v1.1), compared to those without pathologic or clinical response at time of surgery in patients receiving neoadjuvant atezolizumab will be (Cohort 1).

  • The 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: Baseline (within 7 days of Cycle 1 Day 1 atezolizumab; Cohort 1 and 2) to within either 7 days before surgery (Cohort 1) or C1D14 (Cycle 1 Day 14) and C1D21 (Cycle 1 Day 21) atezolizumab (Cohort 2). ]
    The change between pre-treatment and post-treatment SUVmax in lymphoid organs (e.g. lymph nodes) on whole-body [18F]F-AraG PET/MR imaging (Cohort 1 and 2).

  • The correlated change in SUVmax of the primary tumor with the number of tumor-infiltrating T cells in the surgical specimen in patients receiving neoadjuvant atezolizumab (Cohort 1). [ Time Frame: At final imaging (within 7 days before surgery) and at time of surgery (after 1-3 x 3 week cycles of atezolizumab) (Cohort 1) ]
    The correlated change in SUVmax of the primary tumor with the number of tumor-infiltrating CD3+ and CD3+CD8+ T cells in the surgical specimen quantified by immunohistochemistry (IHC) and image analysis in patients receiving neoadjuvant atezolizumab (Cohort 1).

  • The correlated change in SUVmax of the primary and/or metastatic tumor(s) with the number of tumor-infiltrating T cells in the pre-treatment biopsy or resection specimen in patients receiving SOC atezolizumab (Cohort 1 and 2). [ Time Frame: At final imaging (within 7 days before surgery) and at time of biopsy/resection (taken in screening or from surgery) ]
    The correlated change in SUVmax of the primary and/or metastatic tumor(s) with the number of tumor-infiltrating CD3+ and CD3+CD8+ T cells in the pre-treatment biopsy or resection specimen quantified by immunohistochemistry (IHC) and image analysis in patients receiving SOC atezolizumab (Cohort 1 and 2).


Estimated Enrollment: 31
Actual Study Start Date: March 7, 2017
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: October 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1: Neoadjuvant
12 patients who are also enrolled in a companion clinical trial (NCT02451423; Phase 2 study of atezolizumab in non-metastatic bladder transitional cell carcinoma) will undergo whole body PET/MR imaging with [18F]F-AraG within 7 days of initiating atezolizumab and within 7 days before surgery.
Drug: [18F]F-AraG (Cohort 1)
Cohort 1: Administered within 7 days of atezolizumab commencement, and then again within 7 days before surgery
Other Names:
  • 2'-deoxy-2'-fluoro-9-β-D-arabinofuranosylguanine
  • VisAcT
Radiation: PET/MRI Scan (Cohort 1)
Cohort 1: Scan done within 7 days of atezolizumab commencement, and then again within 7 days before surgery
Drug: Atezolizumab (Cohort 1)
Cohort 1: 1200mg every 3 weeks x 1-3 cycles as per companion study (NCT02451423)
Other Name: TECENTRIQ
Experimental: Cohort 2: Standard of Care (SOC)
19 patients who are received standard of care (SOC) atezolizumab will undergo whole body PET/MR imaging with [18F]F-AraG within 7 days of initiating atezolizumab and between Day 14 and Day 21 of Cycle 1 atezolizumab.
Drug: [18F]F-AraG (Cohort 2)
Cohort 2: Administered within 7 days of atezolizumab commencement, and then again between Day 14 and Day 21 of Cycle 1 atezolizumab
Other Names:
  • 2'-deoxy-2'-fluoro-9-β-D-arabinofuranosylguanine
  • VisAcT
Radiation: PET/MRI Scan (Cohort 2)
Cohort 2: Scan done within 7 days of atezolizumab commencement, and then again between Day 14 and Day 21 of Cycle 1 atezolizumab
Drug: Atezolizumab (Cohort 2)
Cohort 2: 1200mg every 3 weeks until disease progression or unacceptable toxicity
Other Name: TECENTRIQ

Detailed Description:

This is a single-center cross-sectional imaging study in patients with localized bladder cancer undergoing neoadjuvant atezolizumab as part of a companion clinical trial (NCT02451423; Phase 2 study of atezolizumab in non-metastatic bladder transitional cell carcinoma), and patients with locally advanced or metastatic bladder cancer receiving standard of care (SOC) atezolizumab. 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. For the SOC cohort, study participants will undergo whole body PET/MR imaging with [18F]F-AraG within 7 days of initiating atezolizumab and between Day 14 and Day 21 of Cycle 1 atezolizumab, where a Simon's two-stage design will be utilized.

A total of 31 patients will be enrolled over an accrual period of approximately 20 months. 12 patients will be enrolled in the neoadjuvant atezolizumab cohort, and approximately 19 patients will be enrolled in the SOC atezolizumab cohort.

Patients will be evaluated one day and one week via telephone visit after each radiopharmaceutical injection for safety follow-up. All adverse events will be recorded. Due to the noninvasive and non-therapeutic nature of the study, potential risks of the study are anticipated to be low.

To the investigator's knowledge, this is the first study to investigate changes in activated T cell localization in the setting of immunotherapy for bladder cancer utilizing functional PET imaging.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age >18 years
  2. Histologically or cytologically documented bladder transitional cell carcinoma
  3. Eligible for with plan to undergo neoadjuvant treatment with atezolizumab followed by surgery as part of companion study (NCT02451423), or planned to undergo treatment with atezolizumab per standard of care
  4. Must have measurable disease by RECIST v1.1 regardless of disease stage (e.g. localized, locally advanced, or metastatic)
  5. In female patients, negative pregnancy test with no plans to become pregnant during the duration of the study
  6. Able to provide informed consent and follow the study guidelines
  7. Archival tumor tissue from biopsy or Transurethral Resection of Bladder Tumor (TURBT) 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:

  1. History of prior treatment with immune checkpoint antibodies (e.g. anti-PD-1, anti-PD-L1, anti-CTLA-4 antibody) or co-stimulatory agonist antibodies (e.g. anti-41BB, anti-OX40)

    a. 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.

  2. Diagnosis of immunodeficiency including history of Human Immunodeficiency Virus (HIV)
  3. Receiving systemic steroid therapy or any form of immunosuppressive therapy within 7 days prior to first injection of [18F]F-AraG.

    a. Topical and inhaled corticosteroids are allowed.

  4. Prior allogeneic stem cell or solid organ transplant
  5. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
  6. Biopsy or resection of the primary tumor within 14 days the first injection of [18F]F-AraG
  7. Contraindication to Magnetic Resonance Imaging (MRI) imaging, as determined through review of the University of California San Francisco (UCSF) MRI screening form by qualified site personnel, which includes the presence of pacemaker, aneurysm clip, implanted device, or severe claustrophobia.
  8. Evidence of active infection within 14 days of study enrollment
  9. Female patients who are pregnant or breastfeeding
  10. Inability to receive furosemide (Lasix) in patients with a primary genitourinary tract tumor (e.g. cancers of the bladder, kidney, ureters, urethra, prostate, penis, vagina, uterus, ovaries, or fallopian tubes), including evidence of the following:

    1. Absence of urine formation over last 24 hours
    2. Active pancreatitis
    3. Hearing problem
    4. History of heart attack
    5. Blood pressure drop upon standing resulting in fainting in the last 6 months
    6. Abnormally low blood pressure (systolic pressure < 80mmHg)
    7. Obstruction to outflow of urinary bladder without presence of catheter
    8. Enlarged prostate causing significant difficulty urinating
    9. Systemic lupus erythematosus
    10. Congestive heart failure
    11. High amount of uric acid in the blood if this value is being followed clinically (> 6mg/dL if female; >7mg/dL if male)
    12. Azotemia with Blood Urea Nitrogen (BUN):Creatinine (Cr) ratio > 20
    13. Alkalosis if documented in the medical record within the past 2 weeks
    14. Diabetes
    15. Gout
    16. Low amount of magnesium in the blood (Mg < 1.5)
    17. Low amount of calcium in the blood (Ca < 8.5)
    18. Low amount of sodium in the blood (Na < 135)
    19. Low amount of potassium in the blood (K < 3.5)
    20. Low amount of chloride in the blood (Cl < 97).
  Contacts and Locations
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): NCT03007719


Contacts
Contact: Julie McCluggage, RN 415-514-8133 Julie.McCluggage@ucsf.edu
Contact: Lissa Gray, NP 415-514-8133 Lissa.Gray@UCSF.edu

Locations
United States, California
University of California, San Francisco Recruiting
San Francisco, California, United States, 94158
Contact: Julie McCluggage, RN    415-514-8133    Julie.McCluggage@ucsf.edu   
Contact: Lissa Gray, NP    415-514-8133    Lissa.Gray@UCSF.edu   
Sponsors and Collaborators
Lawrence Fong
CellSight Technologies, Inc.
Investigators
Principal Investigator: Lawrence Fong, MD University of California, San Francisco
  More Information

Responsible Party: Lawrence Fong, Professor in Residence, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT03007719     History of Changes
Other Study ID Numbers: CC#16709
First Submitted: December 28, 2016
First Posted: January 2, 2017
Last Update Posted: July 19, 2017
Last Verified: July 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Atezolizumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs