Study of Acquired Resistance to Alkylator Chemotherapy in Endocrine Neoplasms

Recruiting

• Conditions: Neuroendocrine (NE) Tumors; Endocrine Cancer

• Registration Number: NCT07121998
• Lead Sponsor: Uppsala University

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2025-03-01
• Study First Submitted: 2025-06-17
• Status Verified: 2025-07
• Study First Submitted QC: 2025-08-10
• Last Update Submitted: 2025-08-10
• Study First Posted: 2025-08-14
• Last Update Posted: 2025-08-14
• Primary Completion: 2028-03-01
• Study Completion: 2030-03-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 94

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (1)

Akademiska Sjukhuset; 🇸🇪 Uppsala, Sweden