Clinical trial NCT02207309 (phase 2, status: terminated)
Conditions: sarcoma
ICD codes: C96.A, C46.9, C96.22, C46.0, C46.2, C92.31, C92.32
Drugs: pazopanib, placebo (for pazopanib)
SMILES: ClCCN(CCCl)P1(=O)NCCCO1, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Reason stopped: 
    poor recruitment
  
Eligibility criteria:

        Inclusion Criteria:

          -  Subjects must provide written informed consent prior to performance of study-specific
             procedures or assessments and must be willing to comply with treatment and follow up

          -  Patients must have histological evidence of high-grade soft tissue sarcoma (grade 2 -
             3) according to the FNLCC grading system, tumor size ≥ 5 cm and deep localization with
             regard to the superficial fascia, excluding the following tumor types:

               -  Embryonal rhabdomyosarcoma

               -  Chondrosarcoma (excluding extraskeletal myxoid chondrosarcoma)

               -  Osteosarcoma (excluding extraskeletal osteosarcoma)

               -  Ewing tumors / primitive neuroectodermal tumor (PNET)

               -  Gastro-intestinal stromal tumors (GIST)

               -  Dermatofibrosarcoma protuberans

          -  Patients who had undergone previous surgery with inadequate margins (tumour-free
             margins ≤1 cm or margins contaminated) are eligible if thermochemotherapy has been
             started within 8 weeks after surgery

          -  Unstained slides and ideally tumour blocks must be available for histological central
             review

          -  Completed 4 to 8 cycles of thermochemotherapy with doxorubicin and ifosfamide at least
             21 days but no more than 42 days prior to study entry

          -  No evidence of disease following completion of first-line thermochemotherapy and
             within ≤ 21 days of study entry

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  No other prior chemotherapy except thermochemotherapy with doxorubicin and ifosfamide

          -  Adequate organ system function

        Exclusion Criteria:

          -  No prior or concurrent second primary malignant tumors (except adequately treated in
             situ carcinoma of cervix, or basal cell carcinoma)

          -  No symptomatic or known Central nervous system (CNS) metastases at baseline

          -  Clinically significant gastrointestinal abnormalities that may increase the risk for
             gastrointestinal bleeding including, but not limited to:

               -  Active peptic ulcer disease

               -  Known intraluminal metastatic lesion/s with risk of bleeding

               -  Inflammatory bowel disease (e.g. ulcerative colitis, Chrohn's disease), or other
                  gastrointestinal conditions with increased risk of perforation

               -  History of abdominal fistula, gastrointestinal perforation, or intra abdominal
                  abscess within 28 days prior to beginning study treatment.

          -  Clinically significant gastrointestinal abnormalities that may affect absorption of
             investigational product including, but not limited to:

               -  Malabsorption syndrome

               -  Major resection of the stomach or small bowel.

          -  Corrected QT interval (QTc) > 480 msecs

          -  History of any one or more of the following cardiovascular conditions within the past
             6 months:

               -  Cardiac angioplasty or stenting

               -  Myocardial infarction

               -  Unstable angina

               -  Coronary artery bypass graft surgery

               -  Symptomatic peripheral vascular disease

               -  Class III or IV congestive heart failure, as defined by the New York Heart
                  Association (NYHA) (See Appendix D for description)

          -  Poorly controlled hypertension (SBP of ≤ 150 mmHg or DBP of ≤95 mmHg is acceptable
             provided that BP will be treated and monitored at least weekly. The goal is to attain
             controlled hypertension within 4 weeks of start of IMP which is defined as grade ≤1
             hypertension CTCAE Version 4.0)

          -  NYHA II at Screening for Patients > 65 years

          -  History of cerebrovascular accident including transient ischemic attack (TIA),
             pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.

        Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulating
        agents for at least 6 weeks are eligible

          -  Major surgery or trauma within 28 days prior to first dose of investigational product
             and/or presence of any non-healing wound, fracture, or ulcer (procedures such as
             catheter placement not considered to be major surgery).

          -  Evidence of active bleeding or bleeding diathesis.

          -  Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that
             increase the risk of pulmonary hemorrhage Note: Lesions infiltrating major pulmonary
             vessels (contiguous tumour and vessels) are excluded; however, the presence of a tumor
             that is touching, but not infiltrating (abutting) the vessels is acceptable (CT with
             contrast is strongly recommended to evaluate such lesions).

               -  Large protruding endobronchial lesions in the main or lobar bronchi are excluded;
                  however, endobronchial lesions in the segmented bronchi are allowed.

               -  Lesions extensively infiltrating the main or lobar bronchi are excluded; however,
                  minor infiltrations in the wall of the bronchi are allowed.

          -  Recent hemoptysis (≥½ teaspoon of red blood within 8 weeks before first dose of study
             drug).

          -  Any serious and/or unstable pre-existing medical, psychiatric, or other condition that
             could interfere with subject's safety, provision of informed consent, or compliance to
             study procedures.

          -  Treatment with any of the following anti-cancer therapies:

               -  radiation therapy, surgery or tumor embolization within 14 days prior to the
                  first dose of pazopanib OR

               -  chemotherapy, immunotherapy, biologic therapy, investigational therapy or
                  hormonal therapy within 14 days or five half-lives of a drug (whichever is
                  longer) prior to the first dose of pazopanib

          -  Administration of any non-oncologic investigational drug within 30 days or 5 half
             lives whichever is longer prior to receiving the first dose of study treatment

          -  Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is
             progressing in severity, except alopecia