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Study of Preoperative Therapy With Pazopanib (Votrient®) to Treat High-risk Soft Tissue Sarcoma (NOPASS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2014 by Heidelberg University
Sponsor:
Collaborators:
Universitätsmedizin Mannheim
Klinikum Frankfurt Höchst
German Cancer Research Center
GlaxoSmithKline
University Hospital Heidelberg
Information provided by (Responsible Party):
Peter Hohenberger, Universitätsmedizin Mannheim
ClinicalTrials.gov Identifier:
NCT01543802
First received: February 10, 2012
Last updated: November 21, 2014
Last verified: November 2014
  Purpose

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),


Condition Intervention Phase
Sarcoma, Soft-tissue
Drug: pazopanib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Window-of-opportunity Study of Preoperative Therapy With Pazopanib (Votrient®) in High-risk Soft Tissue Sarcoma

Resource links provided by NLM:


Further study details as provided by Heidelberg University:

Primary Outcome Measures:
  • Metabolic response rate [ Time Frame: day 22-28 (time of post-treatment PET-CT) ] [ Designated as safety issue: No ]
    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") [ 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: 35
Study Start Date: April 2013
Estimated Study Completion Date: June 2018
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pazopanib Drug: pazopanib
Treatment with pazopanib 800 mg qd for 21 days followed by resection of the tumor after a 7-14 days break
Other Name: Votrient

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Written informed consent prior to performance of study-specific procedures or assessments and must be willing to comply with treatment and follow-up.
  2. Age ≥ 18 years or legal age of consent if different from 18 years.
  3. 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).
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  5. Measurable disease according to RECIST 1.1
  6. 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).
  7. Adequate organ system function
  8. 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.
  9. 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:

  1. 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
  2. Prior malignancy.
  3. History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis.
  4. Prior or concurrent systemic chemotherapy or molecularly targeted therapy for STS or other malignancies within five years before study entry.
  5. Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding.
  6. Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product
  7. Corrected QT interval (QTc) > 480 msecs (calculation according to Bazett).
  8. Presence of uncontrolled infection.
  9. 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)
  10. Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥140 mmHg or diastolic blood pressure (DBP) of ≥ 90mmHg].
  11. Cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.
  12. 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).
  13. Evidence of active bleeding or bleeding diathesis.
  14. Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage.
  15. Recent hemoptysis (more than ½ teaspoon of red blood within 8 weeks before first dose of study drug).
  16. 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.
  17. 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.
  18. 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
  19. 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.
  20. Any ongoing toxicity from prior anti-cancer therapy that is > grade 1 and/or that is progressing in severity, except alopecia.
  Contacts and Locations
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

Contacts
Contact: Ulrich Ronellenfitsch, MD +49-621-3831501 ulrich.ronellenfitsch@umm.de

Locations
Germany
Klinikum Frankfurt-Höchst Recruiting
Frankfurt am Main, Germany, 65929
Contact: Hans-Günter Derigs, MD    +49-69-31063320    derigs@klinikumfrankfurt.de   
Principal Investigator: Hans-Günter Derigs, MD         
German Cancer Research Center, Medical PET Group - Biological Imaging Recruiting
Heidelberg, Germany, 69120
Contact: Antonia Prof. Dr. Antonia Dimitrakopoulou-Strauss, MD    +49-6221-422500    a.dimitrakopoulou-strauss@dkfz.de   
Principal Investigator: Antonia Antonia Dimitrakopoulou-Strauss, MD         
University Hospital Heidelberg / National Centre for Tumor Diseases Recruiting
Heidelberg, Germany, 69120
Contact: Gerlinde Egerer, MD    +49-6221-568002    Gerlinde.Egerer@med.uni-heidelberg.de   
Principal Investigator: Gerlinde Egerer, MD         
Sub-Investigator: Stefan Froehling, MD         
University Hospital Mannheim, Dpt. of Surgery Recruiting
Mannheim, Germany, 68135
Contact: Ulrich Ronellenfitsch, MD    +49-621-3831501    ulrich.ronellenfitsch@umm.de   
Principal Investigator: Peter Hohenberger, MD         
Sponsors and Collaborators
Heidelberg University
Universitätsmedizin Mannheim
Klinikum Frankfurt Höchst
German Cancer Research Center
GlaxoSmithKline
University Hospital Heidelberg
Investigators
Principal Investigator: Peter Hohenberger, MD University Hospital Mannheim, Department of Surgery
  More Information

Additional Information:
No publications provided

Responsible Party: Peter Hohenberger, Head, Division of Surgical Oncology and Thoracic Surgery, Universitätsmedizin Mannheim
ClinicalTrials.gov Identifier: NCT01543802     History of Changes
Other Study ID Numbers: GISG-04
Study First Received: February 10, 2012
Last Updated: November 21, 2014
Health Authority: Germany: Ethics Commission
Germany: Federal Institute for Drugs and Medical Devices
Germany: Federal Office for Radiation Protection

Keywords provided by Heidelberg University:
soft-tissue sarcoma
pazopanib
antiangiogenetic treatment
endothelial progenitor cells
preoperative therapy

Additional relevant MeSH terms:
Sarcoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Connective and Soft Tissue

ClinicalTrials.gov processed this record on November 25, 2014