MedDRA version: 15.1 Level: HLGT Classification code 10041299 Term: Soft tissue sarcomas System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Votrient
Product Name: Pazopanib
Product Code: GW786034
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: PAZOPANIB HYDROCHLORIDE
CAS Number: 635702-64-6
Concentration unit: mg
Sponsors
Klinikum der Universität München
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 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. Note: Informed consent may be obtained prior to start of the specified screening window. Note: Procedures conducted as part of the subject’s routine clinical management (e.g., blood count, imaging study such as bone scan) and obtained prior to signing of informed consent may be utilized for screening or baseline purposes provided these procedures are conducted as specified in the protocol 2. Age = 18 years 3. 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, 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 4. 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 of surgery. The decision of a re-resection after 4 cycles of thermochemotherapy will be made by the multidisciplinary tumor board. 5. Unstained slides and ideally tumour blocks must be available for histological central review 6. 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 7. No evidence of disease following completion of first-line thermochemotherapy and within = 21 days of study entry 8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 9. No other prior chemotherapy except thermochemotherapy with doxorubicin and ifosfamide 10. Adequate organ system function as defined in Table 2 11. Women of childbearing potential must have a negative serum pregnancy test within 14 days of first dose of study treatment and agree to use effective contraception as defined in section 7.1.11 Inclusion criteria during the study and for 14 days following the last dose of investigational product. 12. Male patients with female partners of childbearing potential must meet one of the following criteria: o At least 6 weeks after surgical sterilization by vasectomy with documentation of azoospermia o Correct use of two reliable contraception methods for 14 days before exposure to IMP, through the dosing period, and for at least 21 days after the last dose of IMP. This includes every combination of a hormonal contraceptive (such as oral, injection, transdermal patch, implant, cervical ring) or an IUD/IUS with a barrier method (diaphragm, cervical cap, Lea contraceptive, femidom, or condom). o Complete sexual abstinence for 14 days before exposure to IMP, through the dosing period, and for at least 21 days after the last dose of IMP. 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 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: 1. No prior or concurrent second primary malignant tumors (except adequately treated in situ carcinoma of cervix, or basal cell carcinoma). 2. No symptomatic or known Central nervous system (CNS) metastases at baseline. 3. 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. 4. 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. 5. Corrected QT interval (QTc) > 480 msecs Note: Correction method should be reported in CRF 6. 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) 7. 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) Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. BP must be re-assessed twice with an interval of at least 1h before start of treatment and should be =140/90 mmHg for a subject to be eligible for the study. However, BP of =150/95 mmHg is acceptable provided the above measures are employed. 8. NYHA II at Screening for Patients > 65 years 9. 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 10. 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). 11. Evidence of active bleeding or bleeding diathesis. 12. 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. 13. Recent hemoptysis (=½ teaspoon of red blood within 8 weeks befo
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objective: To compare the effectiveness, as measured by PFS according to RECIST v 1.1, of maintenance pazopanib given as a continuous daily dose over maximally 24 months versus placebo maintenance in patients with high-risk retroperitoneal or visceral soft tissue sarcomas who show no evidence of disease after multimodal treatment including neo- and/or adjuvant doxorubicin / ifosfamide chemotherapy with regional hyperthermia, tumor resection and radiotherapy, if indicated.;Secondary Objective: Secondary objectives: Key secondary objectives: · To describe the toxic effects of pazopanib given in a continuous daily schedule · To determine LPFS, DPFS and OS of treated patients Other secondary objectives are to assess health related quality of life (QOL) as assessed by EORTC QLQC30, and to investigate predictive biomarkers.;Primary end point(s): Primary efficacy endpoint: PFS calculated as time from date of randomization until the date of first objective documentation of disease progression, treatment failure, or death due to any cause, whichever occurs first.;Timepoint(s) of evaluation of this end point: Date of first objective documentation of disease progression, treatment failure, or death due to any cause, whichever occurs first. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints: Key secondary endpoints: · Rates of grade 3 or 4 toxicities during pazopanib or placebo maintenance · Local progression-free survival (LPFS), defined as time from randomization to the date of local tumor relapse or death, whichever occurred first and irrespective of any occurrence of distant metastases · Distant progression-free survival (DPFS), defined as time from randomization to the date of metastasis formation whichever occurred first. · Overall survival (OS) will be calculated from date of randomization to date of death (from any cause). Patients alive will be censored at time of last follow-up. Further secondary endpoints: · QoL: Quality of life questionnaire (QLQ-C30; Appendix B) will be collected at baseline (day -21 to 1), after 3, 6, 9, 12, 15, 18, 21 and 24 months from date of randomization and 3 months after last dose (end of treatment (EOT)). · Biomarker assessment to predict PFS at 2 years from date of randomization;Timepoint(s) of evaluation of this end point: Please refer to E.5.2 Secondary Endpoints | — |
Countries
Germany
Contacts
Public ContactMed. Klinik und Poliklinik III
Klinikum derUniversität München
Outcome results
None listed