E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
non-metastatic sarcoma patients localized in the extremities, trunk and chest wall or the head and neck region |
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E.1.1.1 | Medical condition in easily understood language |
sarcoma localized in extremities, trunk and chest wall or the head and neck region |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039491 |
E.1.2 | Term | Sarcoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10039492 |
E.1.2 | Term | Sarcoma bone |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate the proportion of patients with resection specimens demonstrating induction of a pathological (near) complete remission (≥ 95% tumor regression) |
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E.2.2 | Secondary objectives of the trial |
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) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
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E.4 | Principal 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 |
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E.5 End points |
E.5.1 | 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 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
6 weeks post treatment at surgery |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |