Chemoradiotherapy at soft tissue sarcomas

Phase 1

• Conditions: soft tissue sarcomas; MedDRA version: 20.0Level: HLTClassification code 10041293Term: Soft tissue neoplasms malignant and unspecified NEC (excl sarcomas)System Organ Class: 100000004864; MedDRA version: 20.0Level: HLTClassification code 10024628Term: Liposarcomas malignantSystem Organ Class: 100000004864; MedDRA version: 20.0Level: HLTClassification code 10024190Term: LeiomyosarcomasSystem Organ Class: 100000004864; MedDRA version: 20.0Level: HLTClassification code 10041298Term: Soft tissue sarcomas histology unspecifiedSystem Organ Class: 100000004864; MedDRA version: 20.0Level: HLTClassification code 10016634Term: Fibrosarcomas malignantSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2021-000042-17-NL
• Lead Sponsor: etherlands Cancer Institute

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-12-07
• Last Update Posted: 26 September 2023

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 30

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 radiotherapy and surgery (In other words: either 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 radiotherapy and definitive surgery, patients are allowed to participate;
•WHO Performance Status = 2;
•Able and willing to undergo preoperative radiotherapy;
•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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 24
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 6

Exclusion Criteria

Pathological diagnosis
•Patients with any type soft tissue sarcoma located above the clavicles;
•Patients with recurrent sarcomas who underwent prior radiotherapy to the target lesion (if the primary sarcoma was managed by surgery only and no perioperative radiotherapy, patients are eligible);
•Ewing sarcoma and other PNET family tumors, rhabdomyosarcomas (both pediatric and adult), bone sarcomas;

Concurrent therapies
•Neoadjuvant chemotherapy to be scheduled between end of radiotherapy and definitive surgery is not allowed. (neoadjuvant chemotherapy before start of study radiotherapy is allowed);
•Intention to perform an isolated limb perfusion, instead of a tumor resection;
•Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug;

Medical History
•Prior malignancies; except another malignancy and disease-free for = 5 years, or completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma;
•Prior surgical procedure within 28 days prior to the first dose of durvalumab, excluding minor surgical procedures e.g procedures only recuing local anesthesia.
•Past medical history of interstitial lung disease (ILD ), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease;
•History or presence of myopathy or raised CK >5 x ULN on 2 occasions at screening. CK should not be measured following strenuous exercise or in the presence of a plausible alternative cause of CK increase, which may confound interpretation of the results. If CK levels are significantly elevated at baseline (>5 x ULN) a confirmatory test should be carried out within 5 – 7 days. If the repeat test confirms a baseline CK >5 x ULN, treatment should not be started;

Cardiac function
•Cardiac dysfunction defined as: Myocardial infarction within six months of study entry, NYHA Class II/III/IV heart failure, unstable angina or unstable cardiac arrhythmias;
?Mean resting corrected QT interval (QTcF) > 470 msec obtained from 3 electrocardiograms (ECGs) (QTc interval will be calculated using Fridericia’s formula);
?Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG, e.g., complete left bundle branch block, third degree heart block;
?Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years-of-age. Patients stable on concomitant medications known to prolong the QT interval may be allowed to participate in the study provided that their mean resting corrected QT interval (QTcF) is < 470 msec at baseline and after discussion with the Medical Monitor;

Concurrent and prior medication
•Concomitant treatment with medicines listed as ‘prohibited’ or ‘excluded’ (section 3.1.4);
•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);
•Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients;

Prior and concurrent clinical trials
•Participation in another clinical study with an investigational product during the last 3 months;
•Concurrent enrolment in another clinical study or, unless it is an observational (non-interventional) clinical study o

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified