pazopanib maintenance phase ii

Conditions: Sarcoma

Summary: this trial compares pazopanib to placebo as maintenance treatment over 2 years in patients with retroperitoneal and visceral high-risk soft tissue sarcomas after multimodal treatment including prior neo- and/or adjuvant doxorubicin / ifosfamide chemotherapy with regional hyperthermia.


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

Keywords: high-risk soft tissue sarcoma pazopanib retroperitoneal soft tissue sarcoma visceral soft tissue sarcoma votrient