PASART 2

Phase 1

• Conditions: soft tissue sarcoma; MedDRA version: 19.0Level: HLTClassification code 10041298Term: Soft tissue sarcomas histology unspecifiedSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 19.0Level: PTClassification code 10024627Term: LiposarcomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 19.0Level: PTClassification code 10016632Term: FibrosarcomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 19.0Level: PTClassification code 10049067Term: Spindle cell sarcomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 19.0Level: PTClassification code 10024189Term: LeiomyosarcomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

• Registration Number: EUCTR2015-004134-95-GB
• Lead Sponsor: The Netherlands Cancer Institute

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-06-10
• Last Update Posted: 23 January 2017

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 35

Inclusion Criteria

•Histologically confirmed newly diagnosed intermediate to high grade soft tissue sarcoma localized to the extremities, trunk and chest wall or the head and neck area, for which the standard treatment is a combination of and radiotherapy and surgery(deep seated, > 5cm according to the RECIST 1.1 criteria and/or an anticipated close resection margin, grade II/III according to the FNLCC definition)
•Age = 18 years
•WHO performance status of = 1
•Able and willing to undergo blood sampling for PK and PD analysis
•Able to swallow and retain oral medication
•Able and willing to undergo MRI scanning
•Able and willing to undergo tumor biopsies
•Adequate organ functions as described by the laboratory findings in the table 1. For thyroid function, the T4 and TSH values must be within normal values of the range of the participating centers
•Written informed consent prior to performance of study-specific procedures or assessments and must be willing to comply with treatment and follow up.

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion Criteria

•Prior malignancies; except another malignancy and disease-free for = 5 years, or completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma.
•Patients with recurrent sarcomas (even without prior radiotherapy)
•Ewing sarcoma and other PNET family tumors, rhabdomyosarcomas (both pediatric and adult), osteosarcomas
•Clinically significant gastrointestinal abnormalities which might interfere with oral dosing diagnosed as:
?Active peptic ulcer disease
?Inflammatory bowel disease, ulcerative colitis, 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
?Major resection of the stomach or small bowel
•Poorly controlled hypertension [defined as systolic blood pressure (SBP) of =140 mmHg or diastolic blood pressure (DBP) of = 90mmHg]
Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. Following antihypertensive medication initiation or adjustment, blood pressure (BP) must be re-assessed three times at approximately 2-minute intervals. At least 24 hours must have elapsed between anti-hypertensive medication initiation or adjustment and BP measurement. These three values should be averaged to obtain the mean diastolic blood pressure and the mean systolic blood pressure. The mean SBP / DBP ratio must be <140/90 mmHg (or 150/90 mm Hg, if this criterion is approved by the Principal Investigator) in order for a subject to be eligible for the study.
•Unstable or serious concurrent condition (e.g., active infection requiring systemic therapy)
•Prolongation of corrected QT interval (QTc) > 480 msecs on ECG
•History of any of more of the following cardiovascular conditions within the past 6 months:
?Cardiac angioplasty or stenting
?Myocardial infarction
?Unstable angina
?Symptomatic peripheral vascular disease
?Coronary artery by-pass graft surgery
?Class II, III or IV congestive heart failure as defined by the New York Heart Association (NYHA)
?History of cerebrovascular accident, pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months
•Macroscopic hematuria
•Hemoptysis that is clinically relevant within 4 weeks of first dose of pazopanib
•Evidence of active bleeding or bleeding diathesis
•Prior major surgery or trauma within 28 days prior to first dose of study medication and/or presence of any non-healing wound, fracture, or ulcer
•Chemotherapy or radiation therapy within 2 weeks prior to the first dose of study medication
•Biological therapy or treatment with an investigational agent within 28 days or five half-lives, whichever is longer prior to the first dose of study medication
•Prohibited medications listed in the protocol for 14 days or five half-lives of a drug (whichever is longer) prior to visit 1 and for the duration of the study
•Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib
•Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
•Female patients who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified