18F-FLT PET Imaging in Patients With Advanced Melanoma

July 12, 2019 updated by: Washington University School of Medicine

Early Assessment of Response to Dual Checkpoint Inhibitor Therapy in Patients With Advanced Melanoma Using 18F-FLT PET/CT and PET/MR

In the current study, advanced positron emission tomography/computed tomography (PET/CT) and positron emission tomography/magnetic resonance (PET/MR) imaging methods will be used to validate our hypothesis that melanoma patients receiving Dual-Immune Checkpoint Blockade (DICB) therapy, who ultimately achieve clinical benefit, will have an increase, or "FLARE", in tumor FLT and/or FDG uptake from baseline, as seen after cycle#1 of treatment, and that after 2 cycles of treatment responders will have a decline in FLT and FDG uptake, in comparison to the patients classified as "non-responders". In addition, alterations in tumor apparent diffusion coefficient (ADC) on diffusion-weighted magnetic resonance imaging (DW/MRI) will be evaluated, expecting after cycle#1: transient reductions in ADC due to lymphocyte proliferation, increased cellularity and restriction of water movement in responding patients, with these patients tumors having increased ADC at 2 cycles into therapy associated with tumor necrosis. This study will evaluate rather early PET imaging with FLT and FDG is a useful imaging biomarker of response to DICB.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

4

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed diagnosis of unresectable, stage III or metastatic melanoma.
  • Patients who are eligible to receive combined dual immune-checkpoint blockade therapy with ipilimumab and nivolumab, per referring oncologist.
  • Life expectancy ≥ 6 months.
  • Disease that is measurable. This is defined as lesions measuring at least 10mm on radiologic imaging.
  • The Eastern Cooperative Oncology Group (ECOG) performance status of 1 or better
  • Age ≥18 years.

  • Normal organ and marrow function as defined below

    • Aspartate aminotransferase (AST) (SGOT) or alanine aminotransferase (ALT) (SGPT) ≤2.5 × institutional upper limit of normal (≤5 x upper limit of normal for patient with liver metastasis)
    • Total bilirubin within 1.5 x institutional level of normal or direct bilirubin ≤ upper limit of normal (ULN) for patient with total bilirubin levels > 1.5 ULN)
    • Hemoglobin ≥ 9.0g/dL or ≥5.6mmol/L
    • Absolute neutrophil count ≥1000/mcL
    • Platelets ≥ 75K/mcL
  • Women of child-bearing potential must have a negative urinary or serum pregnancy test within 7 days of baseline imaging.

Exclusion Criteria:

  • Patient may not be receiving any other investigational agents
  • Significant auto-immune disease requiring hospitalization within the past two years or any history of life-threatening auto-immune disease
  • Immunosuppressive therapy including systemic corticosteroids except for maintenance dosing for adrenal insufficiency
  • Known additional malignancy that is progressing or requires active treatment with the exceptions of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
  • Active autoimmune disease or a syndrome that requires systemic steroids or immunosuppressive agents with the exceptions of replacement dose steroids for adrenal insufficiency, vitiligo, resolved childhood asthma/atopy, intermittent use of inhaled steroids, local steroid injections, hypothyroidism stable on hormone replacement, and Sjogren's syndrome
  • Active tuberculosis
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, autoimmune diseases, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Patients with a pacemaker, stainless steel aneurysm clip or any other magnetic resonance (MR) contraindicated implant or foreign body would warrant exclusion from this study. Pacemakers may be reprogrammed or turned off by the strong MRI magnetic field. Radio-frequency (RF) fields in MR can also cause severe heating of pacemaker lead tips. Steel aneurysm clips are prone to torque in the strong MR field which can displace the clips and may damage the vessel, resulting in hemorrhage, and/or death.
  • History of pneumonitis requiring hospitalization or systemic immune suppressive therapy.
  • Pregnant women are excluded from this study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Screening
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: FDG-PET/CT + FLT-PET/CT + PET/MR

-Baseline, Week 3 (between days 14-20), Week 6 (between days 35-41)

  • FDG-PET/CT - Patients required to fast for at least 4 hours prior to FDG administration. Roughly 60 minutes prior to PET/CT imaging, FDG will be administered via IV bolus injection. A CT will be performed immediately before PET imaging. Whole body PET imaging will be performed for a total of about 30 minutes.
  • FLT-PET/CT - Patients required to fast for at least 4 hours prior to FLT administration. Roughly 80 minutes prior to PET/CT imaging, FLT will be administered via IV bolus injection. A CT will be performed immediately before PET imaging. Whole body PET imaging will be performed for a total of about 30 minutes.
  • PET/MR - A limited whole body scan performed immediately following PET/CT imaging when possible. Should be performed at least once at each time-point. This scan will be of a more limited area and be performed for no more than 30 minutes.
Drug: fludeoxyglucose F 18
Other Names:
  • FDG
  • Fludeoxyglucose (18F)
Device: Positron emission tomography-computed tomography
Other Names:
  • PET/CT
Drug: 18F-fluorothymidine
Other Names:
  • FLT
Device: Positron emission tomography-magnetic resonance imaging
Other Names:
  • PET/MR
  • PET/MRI

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Mean difference in FLT uptake between responders and non-responders
Time Frame: Baseline and Week 3
Baseline and Week 3
Mean difference in FLT uptake between responders and non-responders
Time Frame: Baseline and Week 6
Baseline and Week 6

Secondary Outcome Measures

Outcome Measure
Time Frame
Mean difference in FDG uptake between responders and non-responders
Time Frame: Baseline and Week 3
Baseline and Week 3
Mean difference in FDG uptake between responders and non-responders
Time Frame: Baseline and Week 6
Baseline and Week 6
Change in ADC on DW-MRI
Time Frame: Baseline and Week 3
Baseline and Week 3
Change in ADC on DW-MRI
Time Frame: Baseline and Week 6
Baseline and Week 6

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Washington University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 10, 2016

Primary Completion (Actual)

December 31, 2017

Study Completion (Actual)

December 31, 2017

Study Registration Dates

First Submitted

August 31, 2016

First Submitted That Met QC Criteria

August 31, 2016

First Posted (Estimate)

September 7, 2016

Study Record Updates

Last Update Posted (Actual)

July 17, 2019

Last Update Submitted That Met QC Criteria

July 12, 2019

Last Verified

July 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 201602062

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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