Conditions: Melanoma
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 27
Healthy volunteers: no

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.

Arms:
arm 1: This is a single arm study. All participants completed the study interventions which are pembrolizumab treatment, FDG PET, C11-AMT PET and CT scans.

Interventions: intervention 1: FDG PET/CT scan intervention 2: C11-AMT PET scan intervention 3: Pembrolizumab intervention 4: CT scan
Intervention descriptions: intervention 1: 18F-fluorodeoxy glucose (FDG) positron emission tomography (PET) with intravenous (IV) contrast images are obtained before and at the end study treatment (pembrolizumab infusion). intervention 2: 11C-methyl-L-tryptophan (C11-AMT) positron emission tomography (PET) images are obtained before study treatment (pembrolizumab infusion). intervention 3: 200 mg Pembrolizumab IV administered over 30 minutes on day 1. Repeat every 3 weeks for 4 cycles, until progression, or subject withdrawal for other reasons intervention 4: Computerized tomography (CT) images are taken without IV contrast before the treatment (pembrolizumab infusion) and with IV contrast 3 months after the treatment start.

Protocol document:
Prot_SAP_000.pdf: