Phase II clinical study of concurrent Pazopanib for non-metastatic Sarcoma patients to be treated with Radiotherapy, localized in the extremities, trunk and chest wall or the head and neck region.

Phase 2

Completed

Conditions: sarcoma
soft tissue tumor
10028389

Registration Number: NL-OMON47205

Lead Sponsor: Antoni van Leeuwenhoek Ziekenhuis

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 27

Inclusion Criteria

* Histologically confirmed newly diagnosed non-metastatic 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 radiotherapy and surgery (deep seated and/or > 5cm according to the RECIST 1.1 criteria and/or an anticipated close resection margin and/or grade II/III according to the FNCLCC 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 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

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]
* 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 one 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 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 5 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
Note: Lactating females who discontinue nursing prior to the first dose of study drug and agree to refrain from nursing throughout the treatment period and for 14 days following the last dose of study drug are eligible.
AND:
Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered postmenopausal if they are amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
* Women <50 years old would be considered postmenopausal if they hav

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The resection specimen of each patient will evaluated for the individual<br /><br>percentage of tumor regression. For the analysis of this primary endpoint, a<br /><br>patient is either a success (a pathological (near) complete remission being <br /><br>95% tumor regression) or a failure* (< 95% tumor regression). The proportion<br /><br>of patients with resection specimens demonstrating a pathological (near)<br /><br>complete remission will be calculated. The percentage tumor regression is the<br /><br>proportion of the tumor mass replaced with other tissue where the tumor has<br /><br>regressed, usually fibrous or fibro- inflammatory tissue, necrosis,<br /><br>calcifications or acellular mucin pools</p><br>

Secondary Outcome Measures