Melanoma, Pancreas Cancer
Conditions
Brief summary
The goal of this investigator-initiated tumour profiling study is to analyse the relation between genomic alterations and the tumour immune contexture in patients with advanced melanoma and pancreatic cancer with resistance to (immuno)therapy, aiming to identify targets and approaches for future (combination) treatment. The main endpoint of this study is the number of patients for whom both tumour WGS and immune profiles could be adequately obtained. The co-primary endpoint is the frequency of "inflamed" vs "immune excluded/desert" tumours (based on tumour infiltrating immune cells) in patients with i) NRAS/KRAS mutant vs wild-type tumours and ii) High vs low mutational tumour load. Participants will undergo an extra tumour biopsy procedure and venepuncture once during a tumour biopsy procedure done performed as part of standard treatment.
Interventions
PROCEDUREBiopsy
Participants will undergo an extra tumour biopsy procedure and venepuncture once.
Sponsors
Amsterdam UMC, location VUmc
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of locally advanced or metastatic cutaneous/mucosal melanoma or pancreatic cancer, meeting the following characteristics: a. Melanoma i. Patients with histologically proven locally advanced or metastatic melanoma (stage IV), with intrinsic or acquired resistance to treatment with immune checkpoint inhibition (anti-PD1 antibody +/- ipilimumab) ii. Patients with locoregional or distant recurrence either during, or within 3 months after completion or discontinuation of (neo)adjuvant anti-PD1-based immunotherapy for stage III melanoma. b. Pancreatic cancer i. Patients with histologically proven metastatic pancreatic cancer with progression under or after standard first-line chemotherapy with FOLFIRINOX. 2. Patients must be willing and able to provide written informed consent and be willing and able to comply with the study protocol. 3. Patients must be ≥18 years of age. 4. Metastatic or locoregional lesion of which a tumour needle biopsy can be safely obtained according to routine clinical practice.
Exclusion criteria
\- Patients with metastatic or locally advanced lesions which are not considered to be technically and/or safely biopsied.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of tumour WGS and immune profiles | through study completion, an average of 1 year | number of patients for whom both tumour WGS and immune profiles could be adequately obtained |
| "inflamed" vs "immune excluded/desert" tumours | through study completion, an average of 1 year | The co-primary endpoint is the frequency of "inflamed" vs "immune excluded/desert" tumours (based on tumour infiltrating immune cells) in patients with i) NRAS/KRAS mutant vs wild-type tumours and ii) High vs low mutational tumour load |
Secondary
| Measure | Time frame |
|---|---|
| The percentage of patients with evaluable tumour DNA, RNA and (tissue and peripheral) immune profiles | Through study completion, an average of 2 year |
| The frequency of (potentially) actionable genomic alterations | Through study completion, an average of 2 year |
| Differences between the post-immunotherapy and post-chemotherapy mutational/RNA-profiles with pre-treatment profiles (e.g. copy numbers, mutational load, genetic aberrations) of a similar cohort of patients who participated | After study completion, an average of 2 year |
| The relation between tumour and peripheral immune profiles and changes over time in patients with intrinsic vs acquired resistance to immune checkpoint inhibition | After study completion, an average of 2 year |
| The percentage of patients with melanoma with evaluable (phospho)proteomic profiles | After study completion, an average of 2 year |
Countries
Netherlands
Outcome results
None listed