Study of Preoperative Therapy With Pazopanib (Votrient®) to Treat High-risk Soft Tissue Sarcoma (NOPASS)
Primary Purpose
Sarcoma, Soft-tissue
Status
Terminated
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
pazopanib
Sponsored by
About this trial
This is an interventional treatment trial for Sarcoma, Soft-tissue focused on measuring soft-tissue sarcoma, pazopanib, antiangiogenetic treatment, endothelial progenitor cells, preoperative therapy
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
The following tumor types are ineligible
- Embryonal rhabdomyosarcoma
- Chondrosarcoma
- Osteosarcoma
- 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.
Sites / Locations
- Klinikum Frankfurt-Höchst
- German Cancer Research Center, Medical PET Group - Biological Imaging
- University Hospital Heidelberg / National Centre for Tumor Diseases
- University Hospital Mannheim, Dpt. of Surgery
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Pazopanib
Arm Description
Outcomes
Primary Outcome Measures
Metabolic response rate
Metabolic response rate is defined as the proportion of patients achieving a metabolic response, i.e. a 50% reduction of the mean standardized uptake value (SUVmean) in the post-treatment compared to the pre-treatment FDG-PET-CT
Secondary Outcome Measures
Percentage of tumor tissue with regressive alterations upon resection ("Histopathological Response")
Decrease in tumor size in MRI according to RECIST 1.1 criteria
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")
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
Number of patients in which adverse events occur during treatment
Adverse events are graded according to NCI Common Terminology Criteria for Adverse Events v4.0 (NCI CTCAE v4)
Disease-free survival
Local recurrence-free survival
Distant recurrence-free survival
Overall survival
Decrease in vascularisation in MRI according to adapted Choi Criteria
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
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.
Full Information
NCT ID
NCT01543802
First Posted
February 10, 2012
Last Updated
January 22, 2021
Sponsor
Heidelberg University
Collaborators
Universitätsmedizin Mannheim, Klinikum Frankfurt Höchst, German Cancer Research Center, GlaxoSmithKline, University Hospital Heidelberg
1. Study Identification
Unique Protocol Identification Number
NCT01543802
Brief Title
Study of Preoperative Therapy With Pazopanib (Votrient®) to Treat High-risk Soft Tissue Sarcoma
Acronym
NOPASS
Official Title
A Phase II Window-of-opportunity Study of Preoperative Therapy With Pazopanib (Votrient®) in High-risk Soft Tissue Sarcoma
Study Type
Interventional
2. Study Status
Record Verification Date
December 2015
Overall Recruitment Status
Terminated
Why Stopped
slow recruitment
Study Start Date
April 2013 (undefined)
Primary Completion Date
October 2016 (Actual)
Study Completion Date
October 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Heidelberg University
Collaborators
Universitätsmedizin Mannheim, Klinikum Frankfurt Höchst, German Cancer Research Center, GlaxoSmithKline, University Hospital Heidelberg
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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),
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sarcoma, Soft-tissue
Keywords
soft-tissue sarcoma, pazopanib, antiangiogenetic treatment, endothelial progenitor cells, preoperative therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pazopanib
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
pazopanib
Other Intervention Name(s)
Votrient
Intervention Description
Treatment with pazopanib 800 mg qd for 21 days followed by resection of the tumor after a 7-14 days break
Primary Outcome Measure Information:
Title
Metabolic response rate
Description
Metabolic response rate is defined as the proportion of patients achieving a metabolic response, i.e. a 50% reduction of the mean standardized uptake value (SUVmean) in the post-treatment compared to the pre-treatment FDG-PET-CT
Time Frame
day 22-28 (time of post-treatment PET-CT)
Secondary Outcome Measure Information:
Title
Percentage of tumor tissue with regressive alterations upon resection ("Histopathological Response")
Time Frame
day 28-35
Title
Decrease in tumor size in MRI according to RECIST 1.1 criteria
Time Frame
baseline and day 22-28
Title
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")
Description
Absolute values of all parameters of FDG kinetics will be used for discriminant analysis evaluation.
Time Frame
baseline and day 22-28
Title
Number of days for which planned resection is delayed after treatment
Time Frame
day 28-35
Title
Number of patients in which adverse events occur during treatment
Description
Adverse events are graded according to NCI Common Terminology Criteria for Adverse Events v4.0 (NCI CTCAE v4)
Time Frame
day 1-21
Title
Disease-free survival
Time Frame
3 years
Title
Local recurrence-free survival
Time Frame
3 years
Title
Distant recurrence-free survival
Time Frame
3 years
Title
Overall survival
Time Frame
3 years
Title
Decrease in vascularisation in MRI according to adapted Choi Criteria
Description
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.
Time Frame
baseline and day 22-28
Title
Decrease in MRI apparent diffusion coefficient (ADC) values
Description
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.
Time Frame
baseline and day 22-28
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
The following tumor types are ineligible
Embryonal rhabdomyosarcoma
Chondrosarcoma
Osteosarcoma
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter Hohenberger, MD
Organizational Affiliation
University Hospital Mannheim, Department of Surgery
Official's Role
Principal Investigator
Facility Information:
Facility Name
Klinikum Frankfurt-Höchst
City
Frankfurt am Main
ZIP/Postal Code
65929
Country
Germany
Facility Name
German Cancer Research Center, Medical PET Group - Biological Imaging
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
University Hospital Heidelberg / National Centre for Tumor Diseases
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
University Hospital Mannheim, Dpt. of Surgery
City
Mannheim
ZIP/Postal Code
68135
Country
Germany
12. IPD Sharing Statement
Citations:
PubMed Identifier
30843160
Citation
Ronellenfitsch U, Karampinis I, Dimitrakopoulou-Strauss A, Sachpekidis C, Jakob J, Kasper B, Nowak K, Pilz L, Attenberger U, Gaiser T, Derigs HG, Schwarzbach M, Hohenberger P. Preoperative Pazopanib in High-Risk Soft Tissue Sarcoma: Phase II Window-of Opportunity Study of the German Interdisciplinary Sarcoma Group (NOPASS/GISG-04). Ann Surg Oncol. 2019 May;26(5):1332-1339. doi: 10.1245/s10434-019-07183-4. Epub 2019 Mar 6.
Results Reference
derived
PubMed Identifier
26739732
Citation
Ronellenfitsch U, Dimitrakopoulou-Strauss A, Jakob J, Kasper B, Nowak K, Pilz LR, Attenberger U, Gaiser T, Egerer G, Frohling S, Derigs HG, Schwarzbach M, Hohenberger P. Preoperative therapy with pazopanib in high-risk soft tissue sarcoma: a phase II window-of-opportunity study by the German Interdisciplinary Sarcoma Group (GISG-04/NOPASS). BMJ Open. 2016 Jan 6;6(1):e009558. doi: 10.1136/bmjopen-2015-009558.
Results Reference
derived
Links:
URL
http://www.gisg.de
Description
General info on German Interdisciplinary Sarcoma Group, under whose auspices the trial is conducted
Learn more about this trial
Study of Preoperative Therapy With Pazopanib (Votrient®) to Treat High-risk Soft Tissue Sarcoma
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