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.
• 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