Cancer Soft tissue sarcoma
Conditions
Interventions
Experimental arm (A):
Nintedanib 200 mg twice daily orally.
Nintedanib will be given continuously until clinically relevant disease
progression according to the investigator's assessment or until ot
Sponsors
European Organisation for Research in Treatment of Cancer (EORTC)
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: SELECTION CRITERIA, *Written informed consent *Histologically proven advanced, inoperable (medical or surgical) and/or metastatic malignant STS of intermediate or high grade, excluding the following tumor types: * Well-differentiated liposarcoma/atypical lipoma * Embryonal rhabdomyosarcoma * Chondrosarcoma (extraskeletal myxoid chondrosarcoma is eligible) * Osteosarcoma (extraskeletal osteosarcoma is eligible) * Ewing family of tumors/primitive neuroectodermal tumor * Gastro-intestinal stromal tumor * Dermatofibrosarcoma protuberans * For STS where no established grading system exists, or sarcoma subtypes which are very indolent or have an unpredictable clinical behavior, patient entry requires prospective approval in writing, on a case-by-case basis by the Study Coordinator of this trial and EORTC Headquarters (HQ). *Representative formalin fixed, paraffin embedded tumor blocks or unstained tissue slides, either from the primary tumor or a metastatic lesion, must be available for histological central review. * One (and no less or more than one) line of previous systemic chemotherapy for advanced, inoperable and/or metastatic malignant STS. Note: Patients treated in first line with doxorubicin/olaratumab or doxorubicin/placebo +/- olaratumab/placebo maintenance qualify for the trial and such treatment will be considered as one line according to the protocol. * Prior neoadjuvant, adjuvant and or first-line maintenance systemic chemotherapy for locally advanced or metastatic STS is allowed and does count as zero lines of treatment, provided that the disease did not progress during neoadjuvant and/or adjuvant therapy or within 12 weeks after completion of the perioperative treatment. In case the disease progressed during neoadjuvant, adjuvant and or first-line maintenance systemic chemotherapy or within 12 weeks after its completion, the treatment is counted as one line and the patient can theoretically participate in the trial, provided all other selection criteria are met. * Prior to study enrolment, all patients need to have confirmed RECIST 1.1 disease progression based on local investigator's assessment. * Presence of measurable disease according to RECIST 1.1. * Age 18 years or older. * WHO performance status (PS) 0-2. * Life expectancy of at least 3 months. Adequate bone marrow, liver and renal function and coagulation parameters: * neutrophils >= 1.5 x 10^9/L; * hemoglobin >= 9 g/dL (or >= 5.6 mmol/L). Blood transfusions or the administration of hematopoietic growth factors are allowed to achieve these baseline values; * platelets >= 100 x 10^9/L. Platelet transfusions or the administration of hematopoietic growth factors are allowed to achieve these baseline values; * Total bilirubin <= ULN; * Patients with Gilbert syndrome and/or bilirubin < 2xULN and normal AST/ALT are eligible; * SGPT/ALT and SGOT/AST <= 2.5 x ULN for patients with liver metastasis; * SGPT/ALT and SGOT/ AST <= 1.5x ULN for patients without liver metastasis; * Serum creatinine or creatinine clearance/eGFR within normal limits to baseline assessed as per local standard method; * International normalized ratio (INR) <= 2; *Prothrombin time (PT) and partial thromboplastin time (PTT) <= 1.5x ULN *Normal cardiac function (left ventricular ejection fraction (LVEF) * Absenc
Exclusion criteria
Exclusion criteria: See section D4a
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary endpoint: Progression free survival (RECIST 1.1) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoints: · Progression-free rate at 12 weeks (binary) · Overall survival · Objective response rate · Clinical benefit rate · Response duration · Total duration of treatment with nintedanib (including treatment beyond RECIST progression) | — |
Countries
Netherlands
Outcome results
None listed