18F-FLT PET Imaging in Patients With Advanced Melanoma

NCT02891616 | Terminated Phase 1 FDA Drug FDA Device

• 1 other identifier: 201602062
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Melanoma

Keywords

Melanoma; 18F-FLT; 18F-FDG; PET/CT; PET/MR

Outcome Measures

Primary Outcomes (2)

• Mean difference in FLT uptake between responders and non-responders

  Baseline and Week 3

• Mean difference in FLT uptake between responders and non-responders

  Baseline and Week 6

Secondary Outcomes (4)

• Mean difference in FDG uptake between responders and non-responders

  Baseline and Week 3

• Mean difference in FDG uptake between responders and non-responders

  Baseline and Week 6

• Change in ADC on DW-MRI

  Baseline and Week 3

• Change in ADC on DW-MRI

  Baseline and Week 6

Study Arms (1)

FDG-PET/CT + FLT-PET/CT + PET/MR

EXPERIMENTAL

-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; Device: Positron emission tomography-computed tomography; Drug: 18F-fluorothymidine; Device: Positron emission tomography-magnetic resonance imaging

Interventions

fludeoxyglucose F 18 DRUG

Also known as: Fludeoxyglucose (18F), FDG

FDG-PET/CT + FLT-PET/CT + PET/MR

Positron emission tomography-computed tomography DEVICE

Also known as: PET/CT

FDG-PET/CT + FLT-PET/CT + PET/MR

18F-fluorothymidine DRUG

Also known as: FLT

FDG-PET/CT + FLT-PET/CT + PET/MR

Positron emission tomography-magnetic resonance imaging DEVICE

Also known as: PET/MRI, PET/MR

FDG-PET/CT + FLT-PET/CT + PET/MR

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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
• History of pneumonitis requiring hospitalization or systemic immune suppressive therapy.
• Pregnant women are excluded from this study

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Melanoma

Interventions

Fluorodeoxyglucose F18; Positron Emission Tomography Computed Tomography; alovudine

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Deoxyglucose; Deoxy Sugars; Carbohydrates; Positron-Emission Tomography; Tomography, Emission-Computed; Image Interpretation, Computer-Assisted; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Tomography, X-Ray Computed; Multimodal Imaging; Radiographic Image Enhancement; Image Enhancement; Photography; Radiography; Tomography, X-Ray; Radionuclide Imaging; Tomography; Diagnostic Techniques, Radioisotope

Study Officials

• Richard L Wahl, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2016
• First Posted: September 7, 2016
• Study Start: October 10, 2016
• Primary Completion: December 31, 2017
• Study Completion: December 31, 2017
• Last Updated: July 17, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)