Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
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  DRKS00004095

Trial Description

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Title

A Single Arm Multicentre Study Evaluating Pazopanib in First-line Treatment of Poor-risk Patients With Locally Advanced or Metastatic Renal Cell Carcinoma

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Trial Acronym

FLIPPER

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URL of the Trial

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Brief Summary in Lay Language

Patients with advanced renal cell carcinoma (RCC) are classified according to Memorial
Sloan-Kettering Cancer Center (MSKCC) criteria in three risk-groups: favourable,
intermediate and poor. To our knowledge there is only one study which examined the poor risk
group (Hudes et al.), which led to the approval of temsirolimus in this population. However
temsirolimus demonstrated a low response rate of 8.6% according to Response Evaluation
Criteria In Solid Tumor (RECIST) criteria and a Progression free Survival (PFS) of 5.5
months and not all patients are suitable for temsirolimus treatment.

Thus, in clinical routine high-risk patients are also treated with multi Tyrosinkinase
Inhibitors (mTKI). To date, a prospective data acquisition and control of effectiveness of a
mTKI-treatment in high-risk patients has not been conducted.

Pazopanib was recently approved for the first-line treatment of advanced renal cell
carcinoma in Europe and the USA. In the pivotal Phase III trial only nine patients in the
pazopanib group were poor risk according to MSKCC risk criteria and no analysis of this
subgroup was performed. Therefore further data in this group of patients with high medical
need is needed.

Currently there are no well-established predictive or prognostic biomarkers in RCC-mTKI
treatment. This is one of the most important scientific questions in this field. In addition
to the clinical endpoints in this study, the comprehensive biomarker program seeks to
evaluate biomarker candidates and will help to learn more about the effects of pazopanib on
the human organism.

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Brief Summary in Scientific Language

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Do you plan to share individual participant data with other researchers?

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Description IPD sharing plan:

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Organizational Data

  •   DRKS00004095
  •   2013/06/06
  •   2011/12/21
  •   no
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Secondary IDs

  •   2011-001138-40 
  •   NCT01521715  (ClinicalTrials.gov)
  •   iOM-605  (iOMEDICO AG)
  •   2011-001138-40 
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Health Condition or Problem studied

  •   Locally Advanced and/or Metastatic Renal Cell Carcinoma
  •   Carcinoma, Renal Cell
  •   Clear-cell Metastatic Renal Cell Carcinoma
  •   C64 -  Malignant neoplasm of kidney, except renal pelvis
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Interventions/Observational Groups

  •   Drug: Pazopanib
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Characteristics

  •   Interventional
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  •   Single arm study
  •   Open (masking not used)
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  •   Uncontrolled/Single arm
  •   Treatment
  •   Single (group)
  •   IV
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Primary Outcome

- Rate of poor risk patients as defined by the Memorial Sloan-Kettering Cancer Center (MSKCC) criteria who are free of disease progression at 6 months after start of first line treatment with pazopanib.; time frame: from registration until progression of disease or death, assessed up to 6 months

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Secondary Outcome

- Number, characteristics and severity of Adverse Events; time frame: from first dose of pazopanib until 30 days after last dose, death or end of study, whichever came first
- Progression free survival of patients treated with pazopanib; time frame: From date of registration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 20 months
- Overall response rate and duration of response according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1; time frame: From date of registration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 20 months
- Relation between biomarkers and clinical outcome (response, stable disease, progression of disease); time frame: From date of registration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 20 months
- Overall survival of poor risk patients treated with pazopanib.; time frame: from registration until death of any cause assessed up 24 months

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

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Recruitment

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  •   2011/12/31
  •   80
  •   Multicenter trial
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Inclusion Criteria

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

- Histologically confirmed metastatic or locally advanced (defined as non operable
tumor), predominantly clear cell renal cell carcinoma.

- At least three of the following five predictors of short survival are required:

- Lactate Dehydrogenase (LDH) > 1.5 x Upper Limit of Normal (ULN)

- Hemoglobin < Lower Limit of Normal (LLN)

- corrected serum calcium level > 10 mg/dl (2.5 mmol/l)

- time from initial diagnosis of renal-cell carcinoma to occurrence of metastases
of less than 1 year

- Karnofsky Status of 60 or 70

- Karnofsky Status ≥ 60

- Age ≥ 18 years or legal age of consent if greater than 18 years

- Dated and signed written informed consent prior to performance of study-specific
procedures or assessments

- Patients with at least one measurable disease, as defined by RECIST 1.1

- Fresh or archived tumor tissue should be provided for all subjects for biomarker
analysis before or during treatment with pazopanib.

- Adequate organ system function as defined as:

- Subjects may not have had a transfusion within 7 days of screening assessment.

- Subjects receiving anticoagulant therapy are eligible if their International
Normalized Ratio (INR) is stable and within the recommended range for the desired
level of anticoagulation.

- Concomitant elevations in bilirubin and aspartate aminotransferase (AST) or alanine
aminotransferase (ALT) above 1.0 x ULN are not permitted. Patients with Gilbert's
disease and elevation of indirect bilirubin only can be considered like patients with
normal bilirubin.

- Compliance of the patient

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Exclusion Criteria

- Other malignancy. (Patients who have undergone prior radical or partial nephrectomy
for RCC are allowed). Subjects who have had another malignancy and have been
disease-free for five years, or subjects with a history of completely resected
non-melanomatous skin carcinoma or successfully treated in situ carcinoma are
eligible.

- Prior systemic treatment for renal cell carcinoma. (NB: all treatments, neo-adjuvant,
adjuvant or for locally advanced or metastatic RCC are not permitted.)

- History or clinical evidence of central nervous system (CNS) metastases or
leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS
metastases, are asymptomatic, and have had no requirement for steroids or
anti-seizure medication for 6 months prior to first dose of study drug. Screening
with CNS imaging studies (computed tomography (CT) or magnetic resonance imaging
(MRI) is required only if clinically indicated or if the subject has a history of CNS
metastases.

- Clinically significant gastrointestinal abnormalities that may increase the risk for
gastrointestinal bleeding

- Clinically significant gastrointestinal abnormalities that may affect absorption of
investigational product including, but not limited to: Malabsorption syndrome, major
resection of the stomach or small bowel.

- Presence of uncontrolled infection (> grade 2 NCI-CTCAE Version 4.03).

- Corrected QT interval (QTc) > 480 msecs using Bazett's formula

- History of any one or more of the following cardiovascular conditions within the past
6 months:

- Myocardial infarction

- Cardiac angioplasty or stenting

- 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

- History of cerebrovascular accident including transient ischemic attack (TIA),
pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6
months. Note: Subjects with recent DVT who have been treated with therapeutic
anti-coagulating agents for at least 6 weeks are eligible

- Prior major surgery or trauma within 28 days prior to first dose of study drug and/or
presence of any non-healing wound, fracture, or ulcer.

- Evidence of active bleeding or bleeding diathesis.

- Known endobronchial lesions or lesions infiltrating major pulmonary vessels

- Hemoptysis in excess of 2.5 ml (or one half teaspoon ) within 8 weeks prior to first
dose of study drug

- Any serious or unstable pre-existing medical, mental, or other condition, medical,
social or mental impairment or drug abuse that could comprise or interfere with the
subject's safety, provision of informed consent, or compliance to study procedures.

- Unable or unwilling 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 study
drug and for the duration of the study.

- Simultaneous participation in another clinical drug study

- Known infection with Human Immunodeficiency Virus (HIV) or chronic hepatitis B or C

- Pregnant or breast-feeding women. Female subjects of childbearing potential need to
be negatively tested prior and as close to the start of therapy as possible, at least
within 14 days. Women participating in this trial are required to use adequate
contraception. 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

- Subjects who are unable to take oral medication

- Known hypersensitive reaction to any of the components of study treatments

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Addresses

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    • iOMEDICO AG
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    • Ludwig-Maximilians-Universität München, Klinikum Grosshadern
    • Michael Staehler, PD MD 
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    • iOMEDICO AG 
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Sources of Monetary or Material Support

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    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   7
  •   2016/01/14


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