Neuroendocrine (NE) Tumors, Endocrine Cancer
Conditions
Keywords
Alkylating chemotherapy, Treatment resistance
Brief summary
It has been showed that alkylating chemotherapy, particularly the widely used agent temozolomide, may cause high tumor mutational burden (TMB) in certain tumors by causing inactivating mutations in the DNA mismatch repair (MMR) system. This can cause therapy resistance and tumor progression but may also predict response for immunotherapy. Hypermutation is very uncommon in neuroendocrine tumors. However, small studies indicate that around 30% of pancreatic tumors develop high TMB after alkylating chemotherapy. The aim of this study is therefore to study the occurrence and frequency of DNA hypermutation after alkylating chemotherapy in endocrine neoplasms and to investigate non-invasive methods that may capture the development of hypermutation (imaging, ctDNA etc.). This is a prospective multicenter study. 94 patients from Swedish endocrine cancer centers in Uppsala, Stockholm, Göteborg and Lund will be included and divided into two groups. Group A will include patients that are about to start treatment with alkylating chemotherapy. Blood samples for liquid biopsy will be collected at baseline and at follow-up and if the tumor progresses, tissue biopsy will be obtained from two different lesions and analyzed with GMS560. Group B will include patients experiencing tumor progression after having received alkylating chemotherapy at any point in their disease course before. At inclusion, both liquid and tissue biopsy will be obtained and analyzed as described above.
Interventions
PROCEDURECore needle biopsy
Core needle biopsy of metastatic lesions
PROCEDUREPhlebotomy
Phlebotomy of peripheral vein
Sponsors
Uppsala University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Informed consent * Age ≥18 years * Histopathology confirmed endocrine neoplasm * Treatment with alkylating chemotherapy: Arm A; about to start alkylating chemotherapy, or Arm B; at disease progression or recurrence with previous alkylating chemotherapy treatment.
Exclusion criteria
* If planned tissue biopsy: risk factors for biopsy-related complications accordingly to local investigator, including coagulation disorder * Long term treatment with anticoagulant that cannot be temporarily paused without unacceptable risk * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of pancreatic neuroendocrine tumor patients with hypermutation and/or mismatch repair deficiency after treatment with alkylating chemotherapy | Through study completion, an average of 2 years. | Proportion of pancreatic neuroendocrine tumor patients with hypermutation (tumour mutation burden \>30) and/or mismatch repair deficiency (by DNA sequencing or immunohistochemistry) in tissue or liquid biopsy at any timepoint after treatment with alkylating chemotherapy. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Proportion of non-pancreatic endocrine neoplasms that develop hypermutation and/or mismatch repair deficiency after treatment with alkylating chemotherapy | Through study completion, an average of 2 years. | Do non-pancreatic endocrine neoplasms (adrenocortical carcinoma, pheochromocytoma and paraganglioma, lung carcinoids and intestinal neuroendocrine tumors) develop hypermutation (tumor mutation burden \>30) and/or mismatch repair deficiency (by DNA sequencing or immunohistochemistry) in tissue or liquid biopsy at any timepoint after treatment with alkylating chemotherapy? |
Countries
Sweden
Contacts
Primary ContactLovisa Falkman, MD
Outcome results
None listed