Soft Tissue Sarcoma AdultPhase 1SADDRIN-1NCT05116254
Sarcomas and DDR-Inhibition; a Combined Modality Study
A Phase 1 study testing AZD1390 + radiotherapy and AZD1390 + durvlaumab + radiotherapy in people with Soft Tissue Sarcoma Adult, run by The Netherlands Cancer Institute at 1 site in Netherlands.
Trial summary
To assess the safety and tolerability profile, in the pre- and perioperative period (up to 30 days post-surgery), of combined modality treatment (CMT) by administering AZD1390 with or without durvalumab and RT concurrently treating newly diagnosed, non-metastatic soft tissue sarcoma patients with DDRi-based CMT, in… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Soft Tissue Sarcoma Adult
- What is being tested?
- AZD1390 + radiotherapy and AZD1390 + durvlaumab + radiotherapy
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteNetherlands
- Study dates
- 18 Jul 2022to 9 Dec 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
Who may be able to join
- Histologically confirmed newly diagnosed intermediate to high grade soft tissue sarcoma localized to the extremities, for which the standard treatment is a combination of RT and surgery (in other words deep seated and/or > 5cm in largest tumor diameter and/or an anticipated close resection margin and/or grade II/III according to the FNCLCC definition);
- Patients staged by at least a CT scan of the chest (and a CT scan of the abdomen, if deemed indicated according to local practices, e.g. in case of a myxoid liposarcoma). Staging may also be performed by FDG-PET scanning and or total body MRI scans. This staging procedure should not reveal metastatic disease. If, however, a low metastatic burden is detected such that this does not preclude the application of both preoperative RT and definitive surgery, patients are allowed to participate;
- WHO Performance Status ≤ 2;
- Able and willing to undergo preoperative RT;
- Able and willing to undergo definitive surgery;
- Able and willing to comply with regular follow-up visits;
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- Able and willing to swallow and retain oral medication;
- Age ≥ 18 years;
- Body weight >30kg;
- Must have a life expectancy of at least 12 weeks;
- Adequate organ function as defined in Table 5;
- Signed written informed consent prior to any study specific procedures or sampling
Who cannot join
- Patients with any type soft tissue sarcoma located above the clavicles.
- Prior malignancies; except another malignancy and disease-free for ≥ 5 years, or completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma;
- Patients with recurrent sarcomas who underwent prior RT to the target lesion (if the primary sarcoma was managed by surgery only and no perioperative RT, patients are eligible);
- Ewing sarcoma and other PNET family tumors, rhabdomyosarcomas (both pediatric and adult), bone sarcomas;
- Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial;
- Female patients who are pregnant or breast feeding;
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- Intention to perform an isolated limb perfusion, instead of a tumor resection;
- Neoadjuvant chemotherapy to be scheduled between end of RT and definitive surgery is not allowed. (neoadjuvant chemotherapy before start of study RT is allowed);
- Concomitant treatment with medicines listed as 'prohibited' or 'excluded';
- Treatment with moderate and strong inhibitors or inducers of CYP3A4 within 2 weeks before the first dose of study treatment (3 weeks for St John's Wort);
- Additional criteria for durvalumab plus AZD1390:
- Past medical history of allogenic organ transplantation;
- Past medical history of leptomeningeal carcinomatosis;
- Past medical history or active autoimmune or inflammatory disorders
- History or presence of primary immunodeficiency
- Presence of active hepatitis infections or HIV
- Treatment with or prior use of immunosuppressive medication within 2 weeks before the start of treatment
- Prior treatment with anti-PD-1, anti PD-L1 or anti CTLA-4 immunotherapy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Sarcomas and DDR-Inhibition; a Neoadjuvant Phase I Combined Modality Study.
To assess the safety and tolerability profile, in the pre- and perioperative period (up to 30 days post-surgery), of combined modality treatment (CMT) by administering AZD1390 with or without durvalumab and RT concurrently treating newly diagnosed, non-metastatic soft tissue sarcoma patients with DDRi-based CMT, in the specific context of systemic toxicities, wound healing post-surgery and in defining the RP2D for the combinations to support further clinical evaluation.
Read the detailed description
Despite improvements in surgery and radiation for soft tissue sarcoma (STS) patients, local relapses remain an important event for these patients. Most STS subtypes are considered radioresistant and immune cold tumor due to a lack of T-cell infiltration. Investigations into radiosensitization mediated by combining systemic compounds with neoadjuvant radiotherapy (RT) may translate into an increased rate of pathological responses, an increased rate of R0 resections and thus fewer local relapses.
RT is highly potent in inducing DNA damage. Normal cells are usually sufficiently able to repair this damage timely before the next fraction because of an intact DNA Damage Response (DDR) pathway. Frequently, tumor cells have (partial or complete) defects in the DDR pathways rendering them more sensitive to radiation than normal tissues. Inhibition of constituents of the DDR pathways may further widen the therapeutic window of fractionated radiotherapy, and combined with radiotherapy may result in increased tumor T-cell infiltration, creating an opportunity for immunotherapy. Clinical studies into radiosensitization of STS by combinations of radiotherapy and DDR inhibitors with or without immunotherapy are warranted. In this study the DDR candidate inhibitor is new drug candidate AZD1390 targeting ATM (Ataxia Telangiectasia Mutated). The immunotherapy candidate of this study is durvalumab (MEDI4736) targeting PD-L1 (programmed death-ligand 1).
- Conditions
- Soft Tissue Sarcoma Adult
- Being tested
- AZD1390 + radiotherapy, AZD1390 + durvlaumab + radiotherapy
- Keywords
- soft tissue sarcoma, radiotherapy, DNA Damage Response
- Medical subject headings
- Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD1390 + radiotherapyCombination product
AZD1390 combined with preoperative radiotherapy
AZD1390 + durvlaumab + radiotherapyCombination product
AZD1390 combined with durvalumab and preoperative radiotherapy
| Study group | Role | What they receive |
|---|---|---|
| AZD1390 | Other | The experimental oral drug AZD1390 (starting dose once daily 20 mg) will be combined with radiotherapy. Drug will be taken at same day as radiotherapy for 5 weeks at weekdays.
When starting dose of 20 mg is proven safe the next cohort will be 100 and thereafter 200, 400 mg Receives: Combination Product: AZD1390 + radiotherapy |
| AZD1390 + durvalumab | Other | The experimental oral drug AZD1390 (starting dose once daily 20 mg) will be combined with radiotherapy and durvalumab (fixed dose 1500 mg Q4W, until surgery). Drug will be taken at same day as radiotherapy for 5 weeks at weekdays. The dose of AZD1390 in the AZD1390 plus durvalumab cohort will follow the dosing of the AZD1390 only cohort. When starting dose of 20 mg and the next dose of AZD1390 only has been proven safe, the next cohort will be 100 and thereafter 200, 400 mg. Receives: Combination Product: AZD1390 + durvlaumab + radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Drug safety
all adverse events
Measured: 2 years
Drug tolerability
adverse events and more specific woundhealing
Measured: 30 days
Secondary outcomes (4)
Tumor regression
pathological remission
Measured: After 5 weeks of RT and DDRi-based drug treatment
Local control rates
Histopathological response and MRI
Measured: 2 years
Rate of R0 resection
Histological examination of surgical specimens
Measured: Directly after surgery
Rate of R1 resection
Histological examination of surgical specimens
Measured: Directly after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2021
- Study start18 Jul 2022
- Primary completion9 Dec 2025
- Study completion9 Dec 2025
Why it stopped: Endpoint has been reached.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Soft Tissue Sarcoma AdultStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- I: AZD1390 and RT II: AZD1390, durvalumab and RT
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Netherlands Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Leiden University Medical Center, University Medical Center Nijmegen
- Responsible party
- Sponsor
- Investigators
- Rick Haas, MD Prof, Principal investigator, The Netherlands Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05116254
- Sponsor's protocol ID
- M21SAD
- Acronym
- SADDRIN-1
- Status last verified
- Jan 2026
- First submitted
- 14 Oct 2021
- Last updated
- 23 Jan 2026
- 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 23 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sarcomas and DDR-Inhibition; a Neoadjuvant Phase I Combined Modality Study.
- ClinicalTrials.gov ID
- NCT05116254
- Acronym / sponsor ID
- SADDRIN-1 / M21SAD
- Conditions
- Soft Tissue Sarcoma Adult
- Keywords
- soft tissue sarcoma, radiotherapy, DNA Damage Response
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Endpoint has been reached.
- Enrolment
- 12 participants (actual)
- Lead sponsor
- The Netherlands Cancer InstituteUniversity, hospital or other
- Collaborators
- Leiden University Medical Center, University Medical Center Nijmegen
- Study start
- 18 Jul 2022 (actual)
- Primary completion
- 9 Dec 2025 (actual)
- Study completion
- 9 Dec 2025 (actual)
- First posted
- 10 Nov 2021 (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.
To assess the safety and tolerability profile, in the pre- and perioperative period (up to 30 days post-surgery), of combined modality treatment (CMT) by administering AZD1390 with or without durvalumab and RT concurrently treating newly diagnosed, non-metastatic soft tissue sarcoma patients with DDRi-based CMT, in the specific context of systemic toxicities, wound healing post-surgery and in defining the RP2D for the combinations to support further clinical evaluation.
Detailed description
Despite improvements in surgery and radiation for soft tissue sarcoma (STS) patients, local relapses remain an important event for these patients. Most STS subtypes are considered radioresistant and immune cold tumor due to a lack of T-cell infiltration. Investigations into radiosensitization mediated by combining systemic compounds with neoadjuvant radiotherapy (RT) may translate into an increased rate of pathological responses, an increased rate of R0 resections and thus fewer local relapses.
RT is highly potent in inducing DNA damage. Normal cells are usually sufficiently able to repair this damage timely before the next fraction because of an intact DNA Damage Response (DDR) pathway. Frequently, tumor cells have (partial or complete) defects in the DDR pathways rendering them more sensitive to radiation than normal tissues. Inhibition of constituents of the DDR pathways may further widen the therapeutic window of fractionated radiotherapy, and combined with radiotherapy may result in increased tumor T-cell infiltration, creating an opportunity for immunotherapy. Clinical studies into radiosensitization of STS by combinations of radiotherapy and DDR inhibitors with or without immunotherapy are warranted. In this study the DDR candidate inhibitor is new drug candidate AZD1390 targeting ATM (Ataxia Telangiectasia Mutated). The immunotherapy candidate of this study is durvalumab (MEDI4736) targeting PD-L1 (programmed death-ligand 1).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- I: AZD1390 and RT II: AZD1390, durvalumab and RT
| Arm | Type | Receives |
|---|---|---|
| AZD1390 | Other | Combination Product: AZD1390 + radiotherapyThe experimental oral drug AZD1390 (starting dose once daily 20 mg) will be combined with radiotherapy. Drug will be taken at same day as radiotherapy for 5 weeks at weekdays. When starting dose of 20 mg is proven safe the next cohort will be 100 and thereafter 200, 400 mg |
| AZD1390 + durvalumab | Other | Combination Product: AZD1390 + durvlaumab + radiotherapyThe experimental oral drug AZD1390 (starting dose once daily 20 mg) will be combined with radiotherapy and durvalumab (fixed dose 1500 mg Q4W, until surgery). Drug will be taken at same day as radiotherapy for 5 weeks at weekdays. The dose of AZD1390 in the AZD1390 plus durvalumab cohort will follow the dosing of the AZD1390 only cohort. When starting dose of 20 mg and the next dose of AZD1390 only has been proven safe, the next cohort will be 100 and thereafter 200, 400 mg. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Histologically confirmed newly diagnosed intermediate to high grade soft tissue sarcoma localized to the extremities, for which the standard treatment is a combination of RT and surgery (in other words deep seated and/or > 5cm in largest tumor diameter and/or an anticipated close resection margin and/or grade II/III according to the FNCLCC definition);
- Patients staged by at least a CT scan of the chest (and a CT scan of the abdomen, if deemed indicated according to local practices, e.g. in case of a myxoid liposarcoma). Staging may also be performed by FDG-PET scanning and or total body MRI scans. This staging procedure should not reveal metastatic disease. If, however, a low metastatic burden is detected such that this does not preclude the application of both preoperative RT and definitive surgery, patients are allowed to participate;
- WHO Performance Status ≤ 2;
- Able and willing to undergo preoperative RT;
- Able and willing to undergo definitive surgery;
Key exclusion criteria (18 listed)
- Patients with any type soft tissue sarcoma located above the clavicles.
- Prior malignancies; except another malignancy and disease-free for ≥ 5 years, or completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma;
- Patients with recurrent sarcomas who underwent prior RT to the target lesion (if the primary sarcoma was managed by surgery only and no perioperative RT, patients are eligible);
- Ewing sarcoma and other PNET family tumors, rhabdomyosarcomas (both pediatric and adult), bone sarcomas;
- Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial;
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 |
|---|---|---|
| AZD1390 + radiotherapyAZD1390 combined with preoperative radiotherapy | Combination product | AZD1390 |
| AZD1390 + durvlaumab + radiotherapyAZD1390 combined with durvalumab and preoperative radiotherapy | Combination product | AZD1390 + durvalumab |
Primary outcome
Drug safety
Time frame: 2 years
all adverse events
Drug tolerability
Time frame: 30 days
adverse events and more specific woundhealing
4 secondary outcomes
Tumor regression
Time frame: After 5 weeks of RT and DDRi-based drug treatment
Local control rates
Time frame: 2 years
Rate of R0 resection
Time frame: Directly after surgery
Rate of R1 resection
Time frame: Directly after surgery
Results and safety
The study was stopped early (reason given: Endpoint has been reached.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2026.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Rick Haas, MD Prof principal investigator
The Netherlands Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AZD1390 + radiotherapy and AZD1390 + durvlaumab + radiotherapy in people with Soft Tissue Sarcoma Adult, run by The Netherlands Cancer Institute at 1 site in Netherlands.
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 12 inclusion and 18 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: stopped early, as of the sponsor's last update on 23 Jan 2026. 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 Netherlands. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Endpoint has been reached.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Drug safety (time frame: 2 years). The study lists 2 primary outcomes in all. 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 23 Jan 2026.