Combining radiation therapy with a new drug for soft tissue sarcoma treatment

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This clinical trial evaluates the safety and tolerability of a combined modality treatment for patients with newly diagnosed, non-metastatic soft tissue sarcoma. The approach involves administering a DNA Damage Response inhibitor, AZD1390, alongside radiotherapy, with or without the immunotherapy durvalumab. The study aims to assess systemic toxicities, wound healing post-surgery, and to define the recommended phase 2 dose (RP2D) for these combinations. By enhancing the effectiveness of radiotherapy, the trial seeks to improve patient outcomes and reduce local relapses.

Why it matters

Who can join: the full rules

Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* 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

Where it's running

• Antoni van Leeuwenhoek
  Amsterdam, Netherlands Recruiting

Study contacts

• Principal investigator: Rick Haas, MD Prof — The Netherlands Cancer Institute
• Study coordinator: Rick Haas, MD Prof
• Email: r.haas@nki.nl
• Phone: +31205129111

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

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• Combining propranolol and pembrolizumab for advanced soft tissue sarcoma

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.