A phase II multicenter study comparing the efficacy of the oral angiogenesis inhibitor nintedanib with the intravenous cytotoxic compound ifosfamide for treatment of patients with advanced metastatic soft tissue sarcoma after failure of systemic non-oxazaphosporine-based first line chemotherapy for inoperable disease ANITA

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 22

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

See section D4a

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary endpoint: Progression free survival (RECIST 1.1)</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary endpoints:<br /><br>· Progression-free rate at 12 weeks (binary)<br /><br>· Overall survival<br /><br>· Objective response rate<br /><br>· Clinical benefit rate<br /><br>· Response duration<br /><br>· Total duration of treatment with nintedanib (including treatment beyond<br /><br>RECIST progression)</p><br>