Ignite Creation Date:
2024-05-06 @ 9:49 AM
Last Modification Date:
2024-10-26 @ 12:20 PM
Study NCT ID:
NCT03089606
Status:
COMPLETED
Last Update Posted:
2023-11-15
First Post:
2017-02-24
Brief Title:
Pembrolizumab TX-naive Distant Mets Melanoma and Use of C11-AMT PET at Baseline as Imaging Biomarker
Sponsor:
UNC Lineberger Comprehensive Cancer Center
Organization:
UNC Lineberger Comprehensive Cancer Center
Study Overview
Official Title:
Pembrolizumab in Systemic Treatment-Naïve Distant Metastatic Melanoma and Exploration of Use of Baseline 11C-methyl-L-tryptophan C11-AMT PET Imaging as a Predictive Imaging Biomarker of Antitumor Response
Status:
COMPLETED
Status Verified Date:
2023-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Explore the association between intensity of 11C-methyl-L-tryptophan C11-AMT positron emission tomography PET at baseline as measured by mean standardized uptake value SUVmax at each lesion total tumor metabolic volume measurement of intra-tumoral and inter-lesional heterogeneity with objective response rate ORR at 12 weeks as defined via RECIST 11 to pembrolizumab in patients with treatment-naïve metastatic melanoma
Detailed Description:
Objectives
Primary Objective
Explore the association between intensity of C11-AMT PET at baseline as measured by mean standardized uptake value SUVmax at each lesion total tumor metabolic volume measurement of intra-tumoral and inter-lesional heterogeneity with objective response rate ORR at 12 weeks as defined via Response evaluation criteria in solid tumors RECIST 11 to pembrolizumab in patients with Programmed Death PD-1 inhibitor-naïve unresectable American Joint Committee on Cancer AJCC stage III or distant metastatic stage IV melanoma
Secondary Objectives
Estimate ORR CR PR by RECIST 11 at 12 weeks to pembrolizumab in patients with PD-1 inhibitor-naïve unresectable stage III or distant metastatic metastatic melanoma AJCC stage IIIIV
Estimate progression-free survival PFS in patients with unresectable stage III or distant metastatic melanoma treated with pembrolizumab as front-line therapy
Explore associations in SUVmax and other PET parameters eg total tumor metabolic volume measurement of intra-tumoral and inter-lesional heterogeneity between C11-AMT PET and fluorodeoxyglucose FDG-PET at baseline
Explore associations between SUVmax and other PET parameters eg total tumor metabolic volume measurement of intra-tumoral and inter-lesional heterogeneity identified at baseline C11-AMT PET imaging with expression of components of the Indoleamine-pyrrole 23-dioxygenase IDO pathway detected by immunohistochemistry IHC or immunofluorescence L -type amino acid transporter 1 LAT1 IDO tryptophan hydroxylase TPH1 and lymphocyte subtypes CD4 cluster of differentiation 8 CD8 FoxP3 MDSC PD-1PD-L1 and other immune checkpoint pathways lymphocyte-associated gene 3 LAG3 glucocorticoid-induced tumor necrosis factor receptor GITR T-cell immunoglobulin and mucin domain-3 TIM3 in freshly acquired tumor specimens prior to treatment with pembrolizumab
Assess metabolic changes at week 12 or earlier if patient progresses following treatment with pembrolizumab using baseline and week 12 FDG PET
Outline
Screening
Physical exam medical history and laboratory tests as per standard of care Brain Magnetic resonance imaging MRI and Whole body FDG PET Computed tomography CT scan with IV contrast will be performed at least 24 hours before C11-AMT PET scanning Although the FDG PETCT scan with IV contrast is preferred the following baseline measurements may be used if they have occurred within the below specified windows
1 Whole body FDG PETCT scan without IV contrast will be accepted for study purposes ie correlation between baseline FDG PET scan and baseline C11-AMT scan if it has occurred within 28 days before the C11-AMT PET scan In this case the patient will only be required to have a baseline CT scan of the chest abdomen and pelvis also neck if applicable with IV contrast within 28 days of starting pembrolizumab
2 CT scan with intravenous IV contrast will be accepted for study purposes ie baseline tumor assessment if it has occurred within 28 days of starting pembrolizumab In this case the patient will only be required to have a baseline PET scan without CT coregistration 28 days prior to C11-AMT This is to correlate baseline FDG PET with baseline C11-AMT PET parameters
If eligibility criteria are met patients will proceed to Study Related Scans and Biopsy
C11-AMT PET will be performed at least 24 hours before pembrolizumab treatment and at least 24 hours after FDG PETCT scan A research biopsy will be performed before pembrolizumab treatment
After screening and study related scans and biopsy treatment will consist of the following
Pembrolizumab 200mg IV flat dose will be administered over 30 minutes on Day 1 Pembrolizumab dosing will be repeated every 3 weeks until progression or subject withdrawal for other reasons
At the end of treatment
Whole body FDG PETCT scan with IV contrast
Projected Accrual
Up to 25 subjects who have not received prior therapy for their recent diagnosis of distant metastatic melanoma
Primary Objective
Explore the association between intensity of C11-AMT PET at baseline as measured by mean standardized uptake value SUVmax at each lesion total tumor metabolic volume measurement of intra-tumoral and inter-lesional heterogeneity with objective response rate ORR at 12 weeks as defined via Response evaluation criteria in solid tumors RECIST 11 to pembrolizumab in patients with Programmed Death PD-1 inhibitor-naïve unresectable American Joint Committee on Cancer AJCC stage III or distant metastatic stage IV melanoma
Secondary Objectives
Estimate ORR CR PR by RECIST 11 at 12 weeks to pembrolizumab in patients with PD-1 inhibitor-naïve unresectable stage III or distant metastatic metastatic melanoma AJCC stage IIIIV
Estimate progression-free survival PFS in patients with unresectable stage III or distant metastatic melanoma treated with pembrolizumab as front-line therapy
Explore associations in SUVmax and other PET parameters eg total tumor metabolic volume measurement of intra-tumoral and inter-lesional heterogeneity between C11-AMT PET and fluorodeoxyglucose FDG-PET at baseline
Explore associations between SUVmax and other PET parameters eg total tumor metabolic volume measurement of intra-tumoral and inter-lesional heterogeneity identified at baseline C11-AMT PET imaging with expression of components of the Indoleamine-pyrrole 23-dioxygenase IDO pathway detected by immunohistochemistry IHC or immunofluorescence L -type amino acid transporter 1 LAT1 IDO tryptophan hydroxylase TPH1 and lymphocyte subtypes CD4 cluster of differentiation 8 CD8 FoxP3 MDSC PD-1PD-L1 and other immune checkpoint pathways lymphocyte-associated gene 3 LAG3 glucocorticoid-induced tumor necrosis factor receptor GITR T-cell immunoglobulin and mucin domain-3 TIM3 in freshly acquired tumor specimens prior to treatment with pembrolizumab
Assess metabolic changes at week 12 or earlier if patient progresses following treatment with pembrolizumab using baseline and week 12 FDG PET
Outline
Screening
Physical exam medical history and laboratory tests as per standard of care Brain Magnetic resonance imaging MRI and Whole body FDG PET Computed tomography CT scan with IV contrast will be performed at least 24 hours before C11-AMT PET scanning Although the FDG PETCT scan with IV contrast is preferred the following baseline measurements may be used if they have occurred within the below specified windows
1 Whole body FDG PETCT scan without IV contrast will be accepted for study purposes ie correlation between baseline FDG PET scan and baseline C11-AMT scan if it has occurred within 28 days before the C11-AMT PET scan In this case the patient will only be required to have a baseline CT scan of the chest abdomen and pelvis also neck if applicable with IV contrast within 28 days of starting pembrolizumab
2 CT scan with intravenous IV contrast will be accepted for study purposes ie baseline tumor assessment if it has occurred within 28 days of starting pembrolizumab In this case the patient will only be required to have a baseline PET scan without CT coregistration 28 days prior to C11-AMT This is to correlate baseline FDG PET with baseline C11-AMT PET parameters
If eligibility criteria are met patients will proceed to Study Related Scans and Biopsy
C11-AMT PET will be performed at least 24 hours before pembrolizumab treatment and at least 24 hours after FDG PETCT scan A research biopsy will be performed before pembrolizumab treatment
After screening and study related scans and biopsy treatment will consist of the following
Pembrolizumab 200mg IV flat dose will be administered over 30 minutes on Day 1 Pembrolizumab dosing will be repeated every 3 weeks until progression or subject withdrawal for other reasons
At the end of treatment
Whole body FDG PETCT scan with IV contrast
Projected Accrual
Up to 25 subjects who have not received prior therapy for their recent diagnosis of distant metastatic melanoma
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None