Ignite Creation Date:
2025-12-26 @ 5:23 PM
Ignite Modification Date:
2026-01-01 @ 2:32 AM
Study NCT ID:
NCT03089606
Status:
COMPLETED
Last Update Posted:
2023-11-15
First Post:
2017-02-24
Is NOT Gene Therapy:
True
Has Adverse Events:
True
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:
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 1.1) 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) 1.1 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 1.1 at 12 weeks to pembrolizumab in patients with PD-1 inhibitor-naïve unresectable stage III or distant metastatic metastatic melanoma (AJCC stage III/IV).
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 (e.g. 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 (e.g. 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 2,3-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-1/PD-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 PET/CT 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 PET/CT scan without IV contrast, will be accepted for study purposes (i.e. 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 (i.e. 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 PET/CT 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 PET/CT 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) 1.1 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 1.1 at 12 weeks to pembrolizumab in patients with PD-1 inhibitor-naïve unresectable stage III or distant metastatic metastatic melanoma (AJCC stage III/IV).
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 (e.g. 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 (e.g. 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 2,3-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-1/PD-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 PET/CT 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 PET/CT scan without IV contrast, will be accepted for study purposes (i.e. 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 (i.e. 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 PET/CT 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 PET/CT 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:
True
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?: