Study of Acquired Resistance to Alkylator Chemotherapy in Endocrine Neoplasms

NCT07121998 | Recruiting

• 1 other identifier: V1.1
• Study Type: observational
• Target: 94
• Locations: 1 country
• Sites: 1

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.

Conditions

Neuroendocrine (NE) Tumors; Endocrine Cancer

Keywords

Alkylating chemotherapy; Treatment resistance

Outcome Measures

Primary Outcomes (1)

• Proportion of pancreatic neuroendocrine tumor patients with hypermutation and/or mismatch repair deficiency after treatment with alkylating chemotherapy

  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.

  Through study completion, an average of 2 years.

Other Outcomes (1)

• 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.

Study Arms (1)

Patients with endocrine neoplasms who have or will receive treatment with alkylating chemotherapy.

Group A (about to start alkylating chemotherapy) Group B (at progression, previous alkylating chemotherapy)

Procedure: Core needle biopsy; Procedure: Phlebotomy

Interventions

Core needle biopsy PROCEDURE

Core needle biopsy of metastatic lesions

Patients with endocrine neoplasms who have or will receive treatment with alkylating chemotherapy.

Phlebotomy PROCEDURE

Phlebotomy of peripheral vein

Patients with endocrine neoplasms who have or will receive treatment with alkylating chemotherapy.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with endocrine neoplasms who have or will receive treatment with alkylating chemotherapy

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Uppsala University: lead

Study Sites (1)

Akademiska Sjukhuset

Uppsala, Sweden

RECRUITING

MeSH Terms

Conditions

Neoplasms; Endocrine Gland Neoplasms

Interventions

Biopsy, Large-Core Needle; Phlebotomy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biopsy, Needle; Biopsy; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Punctures; Investigative Techniques; Blood Specimen Collection; Therapeutics

Study Officials

• Joakim Crona, MD PhD

  Uppsala University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lovisa Falkman, MD

CONTACT

+46186110000; lovisa.falkman@uu.se

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor, Clinical oncologist

Study Record Dates

• First Submitted: June 17, 2025
• First Posted: August 14, 2025
• Study Start: March 1, 2025
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2030
• Last Updated: August 14, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)