Trial document





This trial has been registered retrospectively.
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  DRKS00003139

Trial Description

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Title

Phase II randomized clinical trial of Pazopanib alone and Pazopanib plus Gemcitabine in relapsed or metastatic soft tissue sarcoma

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Trial Acronym

PAPAGEMO

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URL of the Trial

[---]*

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Brief Summary in Lay Language

In this study can be involved patients with refractory soft tissue sarcoma, after prior chemotherapy. The use of chemotherapy is considered to be the standard therapy in most of the patients. To commend a drug or drug combination is still under investigation. 90 patients will be enrolled in this study. The patients receive pazopanib or the drug combination pazopanib and gemcitabine. The object of both treatment arms will be the decrease or cessation of tumour growth. If the additional administration of gemcitabin offers better response rates will be investigated within the study.

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Brief Summary in Scientific Language

Soft tissue sarcomas (STS) are malignant tumors of connective tissue (mesenchyme). STS have traditionally been managed by wide excision surgery and radiotherapy, being the only curative approach. However, in many patients even optimal local treatment does often not prevent the occurrence of distant metastasis, especially those with high-grade tumors. Primary sites of metastasizes are the lungs but also bone, liver and other organs, depending on the subtype. The use of chemotherapy has been reserved for advanced disease for systemic control.
Patients with relapsed or metastatic soft tissue sarcoma are candidates for clinical trials of new drugs because treatment outcomes remain unsatisfactory and are limited to palliation in the vast majority of cases.
Pazopanib is an orally available, multi-targeted tyrosine kinase inhibitor (TKI), which is currently tested in several clinical trials and diverse tumor types. Targets of this drug are VEGFR, PDGF and c-kit. Currently the approval for renal cell carcinoma in Europe is authorized. Therefore pazopanib represents an attractive therapeutic agent in combination with conventional chemotherapies in relapsed or metastatic STS.
In majority of cases single agent is far less active as combining with conventionell chemotherapy. Several clinical studies suggest that Gemcitabine is a promising partner drug with pazopanib in STS.
The objective of this trial is to assess the efficacy and toxicity of pazopanib alone or pazopanib plus gemcitabine in patients with relapsed or metastatic soft tissue sarcoma.

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Organizational Data

  •   DRKS00003139
  •   2012/01/17
  •   [---]*
  •   yes
  •   Approved
  •   2011-13, Ethikkommission der Medizinischen Fakultät der Martin-Luther-Universität Halle Wittenberg
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Secondary IDs

  •   U1111-1122-1691 
  •   2009-017261-32 
  •   4037327 
  •   KKSH-077  
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Health Condition or Problem studied

  •   relapsed or metastatic soft tissue sarcoma
  •   C49 -  Malignant neoplasm of other connective and soft tissue
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Interventions/Observational Groups

  •   active ingredient: Pazopanib
    trade name: Votrient
    800 mg orally once a day, permanently
    and
    active ingredient: Gemcitabin 1000 mg/m²
    d1, 8, intravenously,
    qd 21, treatment: until progression, ca 6 cycles
  •   active ingredient: Pazopanib
    trade name: Votrient
    800 mg orally once a day, permanently,
    treatment: until progression, ca 6 cycles
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Open (masking not used)
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  •   Active control (effective treament of control group)
  •   Treatment
  •   Parallel
  •   II
  •   No
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Primary Outcome

Progression-free survival Rate (PFSR) after 12 weeks

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Secondary Outcome

•Overall survival (OS)
•Time to Progression (TTP)
•Response Rate (Resist, version 1.1)
•Toxicity (CTCAE, version 4.0)
•Quality of live (EORTC, version 3.0)
[Baseline, d1 of each cycle, end of treatment, every 3 months after progression

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • [---]*
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Recruitment

  •   Actual
  •   2011/09/26
  •   90
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

•Histologically confirmed malignant soft tissue sarcoma (relapsed or metastatic) including any subtypes except:
o Chondrosarcoma
o Osteosarcoma
o Ewing tumors and primitive neuroectodermal tumors
o Gastrointestinal stromal tumors
o Dermofibromatosis sarcoma protuberans
o Inflammatory myofibroblastic sarcoma
o Malignant mesothelioma
o Mixed mesodermal tumors of the uterus
•Relapse or progress after one or two prior chemotherapies including either an antrazyclin or ifosfamid or both. Patients with relapse or progress with liposarcoma or leiomyosarcoma must be offered a treatment with Trabectedin. •Pretreatment with trabectedine is permitted
•ECOG performance status 0-2
•At least 18 years old
•Life expectancy > 3 months
•Patients with at least one measurable lesion according to RECIST criteria (v1.1)
•Able to swallow and retain oral medication
•Adequate organ function as defined in protocol
•A female is eligible to enter and participate in this study if she is either of non childbearing potential (defined in protocol) or childbearing potential with negativ pregnancy test within 2 weeks prior to the first dose of study and agrees to use adequate contraception (as defined in protocol)•Male with childbearing potential agree to use adequate contraception
•Subjects must provide written informed consent prior to performance of study-specific procedures or assessments, and must be willing to comply with treatment and follow up. Procedures conducted as part of the subject’s routine clinical management (e.g., blood count, imaging study) and obtained prior to signing of informed consent may be utilized for screening or baseline purposes provided these procedures are conducted as specified in the protocol.

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Exclusion Criteria

•Patient has received prior treatment with any anti angiogenic drug (including bevacizumab and tyrosine kinase inhibitors)
•Active malignancy or any malignancy in the last 5 years prior to first dose of study drug other than STS.
•History of clinical evidence of CNS metastases or leptomeningeal carcinomatosis (more information see protocol)
•Clinically significant gastrointestinal disorders/ abnormalities (defined in protocol)
•Poorly controlled hypertension (defined in protocol)
•Prolongation of corrected QT interval (QTc) > 480msec
•Clinically significant cardiovascular disease, for example Cerebrovascular accident, myocardial infarction (< 6 months before treatment start), unstable angina, NYHA Class II CHF, arrhythmia requiring medication
•Major surgery or trauma within 28 days or any non- healing wound, fracture or ulcer
•Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to Pazopanib or Gemcitabine
•Presence of uncontrolled infection
•Women who are pregnant or breast feeding
•Chemotherapy or radiotherapy within 14 days prior to the first dose of study drug (defined in protocol)
•Evidence of active bleeding or bleeding diathesis
•Hemoptysis in excess of 2.5 mL (or one half teaspoon) within 8 weeks of first dose of study drug.
•Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels
•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
•History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months
•Unable or unwilling to discontinue use of prohibited medications as defined in protocol for at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study drug and for the duration of the study
•Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is progressing in severity, except alopecia.
•Existing medication with prohibited and interactional drugs with the study drug must be asked in detail. Indispensable use of long term medication with CYP-inhibitors or inductors, explicitly (changes in long term medication is possible; defined in protocol) is prohibited.
•Insufficient liver function (defined in protocol)
•Autoimmune disease
•Uncontrolled hypothyroidism


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Addresses

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    • Universitätsklinikum Halle (Saale)
    • Ernst-Grube-Str. 40
    • 06097  Halle (Saale)
    • Germany
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    • Universitätsklinikum Halle (Saale)
    • Prof. Dr. med.  Hans-Joachim  Schmoll 
    • Ernst-Grube-Str. 40
    • 06097  Halle (Saale)
    • Germany
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    • Universitätsklinikum Halle (Saale)
    • Mr.  Prof. Dr. med.  Hans-Joachim  Schmoll 
    • Ernst-Grube-Str. 40
    • 06097  Halle (Saale)
    • Germany
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Sources of Monetary or Material Support

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    • GlaxoSmithKline GmbH & Co.KG
    • 80339  München
    • Germany
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Status

  •   Recruiting complete, follow-up complete
  •   2016/10/05
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Trial Publications, Results and other Documents

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* This entry means the parameter is not applicable or has not been set.