Clinical trial NCT02891616: 18F-FLT PET Imaging in Patients With Advanced Melanoma
Official title: Early Assessment of Response to Dual Checkpoint Inhibitor Therapy in Patients With Advanced Melanoma Using 18F-FLT PET/CT and PET/MR
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Melanoma
Keywords: Melanoma
18F-FLT
18F-FDG
PET/CT
PET/MR
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2016-09-07
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SCREENING

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.


Eligibility criteria: 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

Primary outcomes:
measure: Mean difference in FLT uptake between responders and non-responders
timeFrame: Baseline and Week 3
measure: Mean difference in FLT uptake between responders and non-responders
timeFrame: Baseline and Week 6
Secondary outcomes:
measure: Mean difference in FDG uptake between responders and non-responders
timeFrame: Baseline and Week 3
measure: Mean difference in FDG uptake between responders and non-responders
timeFrame: Baseline and Week 6
measure: Change in ADC on DW-MRI
timeFrame: Baseline and Week 3
measure: Change in ADC on DW-MRI
timeFrame: Baseline and Week 6
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Richard L Wahl, M.D.
role: PRINCIPAL_INVESTIGATOR
References: