Neuroendocrine (NE) TumorsPROGRESS-TMZNCT07121998
Study of Acquired Resistance to Alkylator Chemotherapy in Endocrine Neoplasms
An observational study of Neuroendocrine (NE) Tumors and Endocrine Cancer, run by Uppsala University at 1 site in Sweden.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neuroendocrine (NE) Tumors, Endocrine Cancer
- What is being tested?
- Core needle biopsy and Phlebotomy
- Type of treatment
- Surgery or procedure
- How many people
- 94 participants
- Where
- 1 siteSweden
- Study dates
- 1 Mar 2025to 1 Mar 2030
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with endocrine neoplasms who have or will receive treatment with alkylating chemotherapy
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Sweden1 site, 1 recruiting
- Recruiting
Akademiska Sjukhuset
Uppsala
Lovisa Falkman, MD, +46186110000, lovisa.falkman@uu.se
About this study
Official title: Longitudinal Biomarker Study in Endocrine Neoplasms to Study Acquired Resistance to Alkylator Chemotherapy
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
- Being tested
- Core needle biopsy, Phlebotomy
- Keywords
- Alkylating chemotherapy, Treatment resistance
- Medical subject headings
- Neoplasms, Endocrine Gland Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Core needle biopsyProcedure or surgery
Core needle biopsy of metastatic lesions
PhlebotomyProcedure or surgery
Phlebotomy of peripheral vein
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: Procedure: Core needle biopsy; Procedure: Phlebotomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Through study completion, an average of 2 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2025
- Study start1 Mar 2025
- Primary completion1 Mar 2028 (estimated)
- Study completion1 Mar 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neuroendocrine (NE) TumorsStudies of the same condition, open and under way.
- More trials run by Uppsala UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 94 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Uppsala University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Joakim Crona, Uppsala University Hospital
- Investigators
- Joakim Crona, MD PhD, Principal investigator, Uppsala University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07121998
- Sponsor's protocol ID
- V1.1
- Acronym
- PROGRESS-TMZ
- Status last verified
- Jul 2025
- First submitted
- 17 Jun 2025
- Last updated
- 14 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Longitudinal Biomarker Study in Endocrine Neoplasms to Study Acquired Resistance to Alkylator Chemotherapy
- ClinicalTrials.gov ID
- NCT07121998
- Acronym / sponsor ID
- PROGRESS-TMZ / V1.1
- Conditions
- Neuroendocrine (NE) Tumors, Endocrine Cancer
- Keywords
- Alkylating chemotherapy, Treatment resistance
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 94 participants (estimated)
- Lead sponsor
- Uppsala UniversityUniversity, hospital or other
- Study start
- 1 Mar 2025 (actual)
- Primary completion
- 1 Mar 2028 (estimated)
- Study completion
- 1 Mar 2030 (estimated)
- First posted
- 14 Aug 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with endocrine neoplasms who have or will receive treatment with alkylating chemotherapy. | – | Procedure: Core needle biopsy, Procedure: PhlebotomyGroup A (about to start alkylating chemotherapy) Group B (at progression, previous alkylating chemotherapy) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with endocrine neoplasms who have or will receive treatment with alkylating chemotherapy
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Core needle biopsyCore needle biopsy of metastatic lesions | Procedure or surgery | Patients with endocrine neoplasms who have or will receive treatment with alkylating chemotherapy. |
| PhlebotomyPhlebotomy of peripheral vein | Procedure or surgery | Patients with endocrine neoplasms who have or will receive treatment with alkylating chemotherapy. |
Primary outcome
Proportion of pancreatic neuroendocrine tumor patients with hypermutation and/or mismatch repair deficiency after treatment with alkylating chemotherapy
Time frame: 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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2025.
- Individual participant dataSharing planned: No
Related trials for Neuroendocrine (NE) Tumors
RecruitingPhase 1
Pilot Study for Detection of PSMA-Low CRPC-NE Tumors With Fluciclovine PET/CT
Advanced Prostate Cancer, Metastatic Prostate Cancer
RecruitingObservational study
Multicenter Study for External Validation of the TB-NET Score
Tumor Burden, Neuroendocrine (NE) Tumors
Not yet recruitingObservational study
Real-World Study of the Safety and Efficacy of Surufatinib in the Treatment of Neuroendocrine Tumors
Neuroendocrine (NE) Tumors
Not yet recruitingPhase 2
AUR103 Calcium in Advanced Neuroendocrine Tumours (BHARAT-3 Study)
Neuroendocrine (NE) Tumors, Advanced NET of GI Origin
Enrolling by invitationPhase 2
Ultralow Dose PET Imaging of 18F-FDOPA
Heathy Volunteer, Parkinsonian Syndromes
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Joakim Crona, MD PhD principal investigator
Uppsala University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Neuroendocrine (NE) Tumors and Endocrine Cancer, run by Uppsala University at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 14 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Lovisa Falkman, MD (+46186110000, lovisa.falkman@uu.se), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of pancreatic neuroendocrine tumor patients with hypermutation and/or mismatch repair deficiency after treatment with alkylating chemotherapy (time frame: Through study completion, an average of 2 years.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2025.