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Locally Advanced and/or Metastatic Renal Cell CarcinomaPhase 4FLIPPERNCT01521715

First Line Pazopanib in Poor Risk Patients With Metastatic Renal Cell Carcinoma

A Phase 4 study testing Pazopanib in people with Locally Advanced and/or Metastatic Renal Cell Carcinoma and Carcinoma, Renal Cell, run by iOMEDICO AG at 8 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Pazopanib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
44 participants
Where
8 sitesGermany
Study dates
24 Jan 2012to 31 Jul 2017
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 17Show fewer
  • 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

Who cannot join

  • 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).
Show all 27Show fewer
  • 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

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

Germany8 sites

  • Urolog. Klinik im Waldkrankenhaus St. Marien, Friedrich-Alexander-Universität

    Erlangen, 91054

  • Universitätsklinikum Essen, Klinik f. Urologie

    Essen, 45122

  • Med. Klinik II, Johann-Wolfgang-Goethe-Universität

    Frankfurt, 60590

  • Medizinisches Versorgungszentrum (MVZ) Osthessen GmbH

    Fulda, 36043

  • Universitätsmedizin Greifswald

    Greifswald, 17475

  • Medizinische Hochschule Hannover

    Hanover, 30625

  • Ludwig-Maximilians-Universität (LMU) München, Klinikum Grosshadern

    München, 81377

  • Universitätsklinikum Münster

    Münster, 48149

Other trials in Germany

About this study

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

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.

Read more

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.

Being tested
Pazopanib
Medical subject headings
Carcinoma, Renal Cell, Clear-cell metastatic renal cell carcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PazopanibDrug

    Also called Votrient

    800 mg (2x400mg) pazopanib per day should be taken orally without food at least one hour before or two hours after a meal until progression or occurrence of intolerable toxicity.

Study groups in NCT01521715
Study groupRoleWhat they receive
PazopanibExperimental800 mg (2x400mg) pazopanib per day
Receives: Drug: Pazopanib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: from registration until progression of disease or death, assessed up to 6 months

Secondary outcomes (5)

  1. Overall survival of poor risk patients treated with pazopanib.

    Measured: from registration until death of any cause assessed up 24 months

  2. Number, characteristics and severity of Adverse Events

    Measured: from first dose of pazopanib until 30 days after last dose, death or end of study, whichever came first

  3. Progression free survival of patients treated with pazopanib

    Measured: 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

  4. Overall response rate and duration of response according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1

    Measured: 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

  5. Relation between biomarkers and clinical outcome (response, stable disease, progression of disease)

    Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Jan 2012 (estimated)
  2. Study start24 Jan 2012
  3. Primary completion30 Jun 2017
  4. Study completion31 Jul 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
44 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01521715
Sponsor's protocol ID
iOM-605
Other IDs
2011-001138-40
Acronym
FLIPPER
Status last verified
Aug 2017
First submitted
21 Dec 2011
Last updated
23 Aug 2017
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • Staehler M, Panic A, Goebell PJ, Merling M, Potthoff K, Herrmann E, de Geeter P, Vannier C, Hogrefe C, Marschner N, Grunwald V. First-line pazopanib in intermediate- and poor-risk patients with metastatic renal cell carcinoma: Final results of the FLIPPER trial. Int J Cancer. 2021 Feb 15;148(4):950-960. doi: 10.1002/ijc.33238. Epub 2020 Aug 18.

    PubMed 32738823

  • Nel I, Gauler TC, Bublitz K, Lazaridis L, Goergens A, Giebel B, Schuler M, Hoffmann AC. Circulating Tumor Cell Composition in Renal Cell Carcinoma. PLoS One. 2016 Apr 21;11(4):e0153018. doi: 10.1371/journal.pone.0153018. eCollection 2016.

    PubMed 27101285

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Pazopanib in people with Locally Advanced and/or Metastatic Renal Cell Carcinoma and Carcinoma, Renal Cell, run by iOMEDICO AG at 8 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01521715, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Aug 2017.

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