Clinical trial NCT03888950: Interim FDG PET-CT in Melanoma Metastatic Patient's Treated by Anti-PD1 Therapy
Official title: Early Response Assessment With Interim FDG PET-CT Imaging in Patients With Advanced Melanoma Treated by Immune Checkpoint Inhibitors Therapy Anti-PD1
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Metastatic Melanoma
Lead sponsor: Centre Hospitalier Universitaire de Nice
Sponsor class: OTHER
First posted: 2019-03-25
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: The objective of this study is to assess whether FDG (18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose) PET-CT could be an early predictive method of therapeutic response to anti-PD-1 immunotherapy in metastatic melanoma after 2 cycles of ANTI-PD1.

20 patients will be enrolled and undergo three PET/CT scans: a baseline PET-CT, an early research PET-CT after 2 cycles of anti-PD1 (PET1) and a PET-CT at 3 months of initiation of treatment. Treatment response on FDG PET-CT will be assessed according to PERCIST criteria.

Detailed description: The management and prognosis of patients with metastatic cutaneous melanoma have changed dramatically with the advent of immunotherapy, especially anti-PD-1 antibodies. These immune-checkpoint inhibitor block the programmend cell death receptor 1 (PD1). Currently, two anti-PD-1 antibodies, nivolumab and pembrolizumab are available. Recent data for pembrolizumab show that the overall survival rate at almost 3 years is 50% and the overall response rate is 42%. Despite these results so far never achieved, about 60% of patients do not respond to anti-PD-1 immunotherapy and, at present, no clinical, imaging or biological markers are predictive of the therapeutic response. The identification of such markers is essential in order to guide the clinician in the choice of optimal treatment.

The objective of this study is to assess whether FDG (18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose) PET-CT could be an early predictive method of therapeutic response to anti-PD-1 immunotherapy in metastatic melanoma.

The anti-tumor immune response to anti-PD-1 is related to the activation of immune cells infiltrating the tumor, in particular CD8+ (cluster of differentiation 8) T cells whose phenotype is that of "exhausted T cells". This immune activation is such that it sometimes causes (about 10% of cases) a transient increase in the size and/or number of lesions. This phenomenon, has been called "pseudo-progression" and it cannot be interpreted routinely by RECIST1.1 criteria. The exact kinetics and timing of CD8+ T cell activation leading to response to treatment is still unknown. It is possible that this cellular activation has an early metabolic translation detectable by 18FDG PET-CT. The investigator's hypothesis is that early 18FDG PET-CT, ie after 2 cycles of anti-PD1 in metastatic patient melanoma, could be predictive of the therapeutic response. 20 patients will be enrolled and undergo three PET/CT scans: a baseline PET-CT (PET0) before the start of anti-PD1 treatment, an early PET-CT after 2 cycles of anti-PD1 (PET1) and a third PET-CT after 3 months of initiation of treatment. Treatment response on FDG PET will be assessed according to PERCIST criteria. Changes in FDG uptake will be correlated with blood results.

Eligibility criteria: Inclusion Criteria:

* Age greater than or equal to 18 years,
* Patient with advanced melanoma proved histologically, not BRAF mutated, BRAFV600 mutated and wild mutated, cutaneous or unknown primary melanoma having an indication of treatment with anti-PD-1 immunotherapy by nivolumab or Pembrolizumab,
* Patient having social insurance,
* Patient who has signed informed consent.

Exclusion Criteria:

* Age less than 18 years,
* Patient with ocular or mucosal melanoma,
* Contraindication to PET CT examination: Severe claustrophobia, unbalanced diabetes (fasting hairy blood glucose ≥ 11 mmol),
* Patient with only metastatic lesions less than 8 mm in size, with the exception of pulmonary nodules,
* HIV and/or HCV (hepatitis C virus) and/or HBV (hepatitis B virus) positive serology, active autoimmune disease,
* Withdrawal of informed consent,
* Metastatic disease not confirmed histologically.

Primary outcomes:
measure: Quantifying changes in FDG uptake according to PERCIST criteria:Single-lesion analysis
timeFrame: Before the start of anti-PD1 treatment (PET0)(day 0), after 2 cycles of anti-PD1 (PET1) (between day 21 and day 31) and after 3 months of initiation of treatment(PET2)
measure: Quantifying changes in FDG uptake according to PERCIST criteria: Five lesion analysis
timeFrame: Before the start of anti-PD1 treatment (PET0)(day 0), after 2 cycles of anti-PD1 (PET1) (between day 21 and day 31) and after 3 months of initiation of treatment(PET2)
measure: Determine the number of lesions
timeFrame: Before the start of anti-PD1 treatment (PET0)(day 0), after 2 cycles of anti-PD1 (PET1) (between day 21 and day 31) and after 3 months of initiation of treatment(PET2)
Secondary outcomes:
measure: Analysis of SUL peak of the most avid lesions
timeFrame: Before the start of anti-PD1 treatment (PET0)(day 0), after 2 cycles of anti-PD1 (PET1) (between day 21 and day 31) and after 3 months of initiation of treatment(PET2)
Other outcomes:
Locations:
city: Nice
country: France
facility: CHU de Nice
state: Chu de Nice
Study officials:
affiliation: Centre Hospitalier Universitaire de Nice
name: Micheline RAZZOUK-CADET, MD
role: PRINCIPAL_INVESTIGATOR
References: