non-metastatic sarcoma patients localized in the extremities, trunk and chest wall or the head and neck region MedDRA version: 18.1 Level: PT Classification code 10039491 Term: Sarcoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 18.1 Level: LLT Classification code 10039492 Term: Sarcoma bone System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: votrient
Pharmaceutical Form: Film-coated tablet
Sponsors
The Netherlands Cancer Institute
Eligibility
Sex/Gender
All
Inclusion criteria
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 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 WHO 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 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 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
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 • 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 cardiovascular conditions 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 • Female patients who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the proportion of patients with resection specimens demonstrating induction of a pathological (near) complete remission (= 95% tumor regression);Secondary Objective: To study tumour changes to pre-operative pazopanib and radiotherapy measured by diffusion-weighted and/or blood oxygenation level-dependent MR imaging (DW-MRI or BOLD-MRI), to assess tolerability and toxicity profile of pazopanib with radiotherapy in the pre-operative setting, to determine response to pazopanib and radiotherapy by RECIST 1.1. criteria, to describe any pathological evidence of tumor regression after pre-operative pazopanib and radiotherapy, to determine local control rates, to investigate the rate of R0 and R1 resections, to investigate the incidence of post-operative wound complications, to investigate recurrence rate at 5 years (local and/or distant disease);Primary end point(s): The resection specimen of each patient will evaluated for the individual percentage of tumor regression. For the analysis of this primary endpoint, a patient is either a “success” (a pathological (near) complete remission being = 95% tumor regression) or a “failure” (< 95% tumor regression). The proportion of patients with resection specimens demonstrating a pathological (near) complete remission will be calculated. The percentage tumor regression is the proportion of the tumor mass replaced with other tissue where the tumor has regressed, usually fibrous or fibro- inflammatory tissue, necrosis, calcifications or acellular mucin pools;Timepoint(s) of evaluation of this end point: 6 weeks post treatment at surgery | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): not applicable;Timepoint(s) of evaluation of this end point: not applicable | — |
Countries
Netherlands
Contacts
Public ContactDirector
The Netherlands Cancer Institute
Outcome results
None listed