Study of Preoperative Therapy With Pazopanib (Votrient®) to Treat High-risk Soft Tissue Sarcoma (NOPASS)
Verified January 2014 by Heidelberg University
Klinikum Frankfurt Höchst
German Cancer Research Center
Information provided by (Responsible Party):
Peter Hohenberger, University Hospital Mannheim
First received: February 10, 2012
Last updated: January 24, 2014
Last verified: January 2014
The purpose of this study is to examine if a short-term treatment with pazopanib, an oral drug inhibiting the growth of blood vessel, can reduce the metabolism of soft-tissue sarcomas and thus facilitate their resection when given prior to surgery. Moreover, the study assesses the prognostic and predictive value of several new biomarkers (endothelial progenitor cells, soluble vascular epithelial growth factor),
||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||A Phase II Window-of-opportunity Study of Preoperative Therapy With Pazopanib (Votrient®) in High-risk Soft Tissue Sarcoma
Primary Outcome Measures:
Secondary Outcome Measures:
- Percentage of tumor tissue with regressive alterations upon resection ("Histopathological Response") [ Time Frame: day 28-35 ] [ Designated as safety issue: No ]
- Decrease in tumor size in MRI according to RECIST 1.1 criteria [ Time Frame: baseline and day 22-28 ] [ Designated as safety issue: No ]
- Change of FDG influx as well as of transport rates k1-k4 and distribution volume VB and fractal dimension in dynamic PET-CT ("Dynamic PET-CT Response") [ Time Frame: baseline and day 22-28 ] [ Designated as safety issue: No ]
Absolute values of all parameters of FDG kinetics will be used for discriminant analysis evaluation.
- Number of days for which planned resection is delayed after treatment [ Time Frame: day 28-35 ] [ Designated as safety issue: Yes ]
- Number of patients in which adverse events occur during treatment [ Time Frame: day 1-21 ] [ Designated as safety issue: Yes ]
Adverse events are graded according to NCI Common Terminology Criteria for Adverse Events v4.0 (NCI CTCAE v4)
- Disease-free survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- Local recurrence-free survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- Distant recurrence-free survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- Decrease in vascularisation in MRI according to adapted Choi Criteria [ Time Frame: baseline and day 22-28 ] [ Designated as safety issue: No ]
Adapted Choi Criteria as defined ín Stacchiotti S, Collini P, Messina A, Morosi C, Barisella M, Bertulli R, et al. High-grade soft-tissue sarcomas: tumor response assessment--pilot study to assess the correlation between radiologic and pathologic response by using RECIST and Choi criteria. Radiology 2009;251(2):447-56.
- Decrease in MRI apparent diffusion coefficient (ADC) values [ Time Frame: baseline and day 22-28 ] [ Designated as safety issue: No ]
ADC values as defined by Dudeck O, Zeile M, Pink D, Pech M, Tunn PU, Reichardt P, et al. Diffusion-weighted magnetic resonance imaging allows monitoring of anticancer treatment effects in patients with soft-tissue sarcomas. J Magn Reson Imaging 2008;27(5):1109-13.
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||June 2015 (Final data collection date for primary outcome measure)
Treatment with pazopanib 800 mg qd for 21 days followed by resection of the tumor after a 7-14 days break
Other Name: Votrient
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- Written informed consent prior to performance of study-specific procedures or assessments and must be willing to comply with treatment and follow-up.
- Age ≥ 18 years or legal age of consent if different from 18 years.
- Non-metastatic primary tumor or locoregional recurrence of histologically confirmed high-risk (G2/3, diameter ≥5 cm) soft tissue sarcoma (STS) of any location (extremities, girdle, trunk, retroperitoneum); or metachronous solitary metastasis of STS for which surgical resection is planned according to the individual choice of the multidisciplinary treatment team (no grade or size restrictions apply for metastasis).
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Measurable disease according to RECIST 1.1
- Resectable and solitary tumor, as assessed by the investigator based on staging exams (CT scan of the chest, CT or MRI of the abdomen, MRI of the limb in case of extremity STS).
- Adequate organ system function
- 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, during the study and until after surgery has been performed.
- Female subjects who are lactating should discontinue nursing prior to the first dose of study drug and should refrain from nursing throughout the treatment period and for 14 days following the last dose of study drug.
The following tumor types are ineligible
- Embryonal rhabdomyosarcoma
- Ewing tumors / PNET
- Gastro-intestinal stromal tumors
- Dermofibromatosis sarcoma protuberans
- Inflammatory myofibroblastic sarcoma
- Malignant mesothelioma
- Prior malignancy.
- History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis.
- Prior or concurrent systemic chemotherapy or molecularly targeted therapy for STS or other malignancies within five years before study entry.
- Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding.
- Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product
- Corrected QT interval (QTc) > 480 msecs (calculation according to Bazett).
- Presence of uncontrolled infection.
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)
- Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥140 mmHg or diastolic blood pressure (DBP) of ≥ 90mmHg].
- Cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.
- 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 are not considered to be major surgery).
- Evidence of active bleeding or bleeding diathesis.
- Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage.
- Recent hemoptysis (more than ½ teaspoon of red blood within 8 weeks before first dose of study drug).
- Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.
- Inability or unwillingness to discontinue use of prohibited medications for at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of investigational product and for the duration of the study.
Treatment with any of the following therapies:
- radiation therapy, surgery targeting the lesion under study other than incisional biopsy, or tumor embolization, prior to the first dose of pazopanib OR
- chemotherapy, immunotherapy, biologic therapy, antiangiogenic therapy, investigational therapy or hormonal therapy, targeting the lesion under study, prior to the first dose of pazopanib OR
- chemotherapy, immunotherapy, biologic therapy, antiangiogenic therapy, investigational therapy or hormonal therapy, targeting any other lesion / disease, within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib
- Administration of any non-oncologic investigational drug within 30 days or 5 half lives whichever is longer prior to receiving the first dose of study treatment.
- Any ongoing toxicity from prior anti-cancer therapy that is > grade 1 and/or that is progressing in severity, except alopecia.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01543802
|Frankfurt am Main, Germany, 65929 |
|Contact: Hans-Günter Derigs, MD +49-69-31063320 email@example.com |
|Principal Investigator: Hans-Günter Derigs, MD |
|German Cancer Research Center, Medical PET Group - Biological Imaging
|Heidelberg, Germany, 69120 |
|Contact: Antonia Prof. Dr. Antonia Dimitrakopoulou-Strauss, MD +49-6221-422500 firstname.lastname@example.org |
|Principal Investigator: Antonia Antonia Dimitrakopoulou-Strauss, MD |
|University Hospital Mannheim, Dpt. of Surgery
|Mannheim, Germany, 68135 |
|Contact: Ulrich Ronellenfitsch, MD +49-621-3831501 email@example.com |
|Principal Investigator: Peter Hohenberger, MD |
Klinikum Frankfurt Höchst
German Cancer Research Center
||Peter Hohenberger, MD
||University Hospital Mannheim, Department of Surgery
No publications provided
||Peter Hohenberger, Head, Division of Surgical Oncology and Thoracic Surgery, University Hospital Mannheim
History of Changes
|Other Study ID Numbers:
|Study First Received:
||February 10, 2012
||January 24, 2014
||Germany: Ethics Commission
Germany: Federal Institute for Drugs and Medical Devices
Germany: Federal Office for Radiation Protection
Keywords provided by Heidelberg University:
endothelial progenitor cells
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on July 26, 2014
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type