Sarcomas and DDR-Inhibition; a Combined Modality Study

NCT05116254 | Terminated Phase 1

• 1 other identifier: M21SAD
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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 the specific context of systemic toxicities, wound healing post-surgery and in defining the RP2D for the combinations to support further clinical evaluation.

Conditions

Soft Tissue Sarcoma Adult

Keywords

soft tissue sarcoma; radiotherapy; DNA Damage Response

Outcome Measures

Primary Outcomes (2)

• Drug safety

  all adverse events

  2 years

• Drug tolerability

  adverse events and more specific woundhealing

  30 days

Secondary Outcomes (4)

• Tumor regression

  After 5 weeks of RT and DDRi-based drug treatment

• Local control rates

  2 years

• Rate of R0 resection

  Directly after surgery

• Rate of R1 resection

  Directly after surgery

Study Arms (2)

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

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.

Combination Product: AZD1390 + durvlaumab + radiotherapy

Interventions

AZD1390 + radiotherapy COMBINATION_PRODUCT

AZD1390 combined with preoperative radiotherapy

AZD1390

AZD1390 + durvlaumab + radiotherapy COMBINATION_PRODUCT

AZD1390 combined with durvalumab and preoperative radiotherapy

AZD1390 + durvalumab

Eligibility Criteria

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

You may qualify if:

• 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;
• 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

You may not qualify if:

• 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;
• 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

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead
• Leiden University Medical Center: collaborator
• University Medical Center Nijmegen: collaborator

Study Sites (1)

Antoni van Leeuwenhoek

Amsterdam, 1066CX, Netherlands

Location

MeSH Terms

Conditions

Sarcoma

Interventions

AZD1390; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Rick Haas, MD Prof

  The Netherlands Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: I: AZD1390 and RT II: AZD1390, durvalumab and RT

Study Record Dates

• First Submitted: October 14, 2021
• First Posted: November 10, 2021
• Study Start: July 18, 2022
• Primary Completion: December 9, 2025
• Study Completion: December 9, 2025
• Last Updated: January 23, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)