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

NCT01521715 | Completed Phase 4

• 2 other identifiers: iOM-6052011-001138-40
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 8

Brief 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. 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.

Conditions

Locally Advanced and/or Metastatic Renal Cell Carcinoma; Carcinoma, Renal Cell; Clear-cell Metastatic Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (5)

• Overall survival of poor risk patients treated with pazopanib.

  from registration until death of any cause assessed up 24 months

• Number, characteristics and severity of Adverse Events

  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

  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

  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)

  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

Study Arms (1)

Pazopanib

EXPERIMENTAL

800 mg (2x400mg) pazopanib per day

Drug: Pazopanib

Interventions

Pazopanib DRUG

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.

Also known as: Votrient

Pazopanib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• iOMEDICO AG: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (8)

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

Erlangen, 91054, Germany

Location

Universitätsklinikum Essen, Klinik f. Urologie

Essen, 45122, Germany

Location

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

Frankfurt, 60590, Germany

Location

Medizinisches Versorgungszentrum (MVZ) Osthessen GmbH

Fulda, 36043, Germany

Location

Universitätsmedizin Greifswald

Greifswald, 17475, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

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

München, 81377, Germany

Location

Universitätsklinikum Münster

Münster, 48149, Germany

Location

Related Publications (2)

• 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.

  PMID: 32738823 DERIVED

• 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.

  PMID: 27101285 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell; Clear-cell metastatic renal cell carcinoma

Interventions

pazopanib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Michael Staehler, PD MD

  Ludwig-Maximilians-Universität München, Klinikum Grosshadern

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2011
• First Posted: January 31, 2012
• Study Start: January 24, 2012
• Primary Completion: June 30, 2017
• Study Completion: July 31, 2017
• Last Updated: August 23, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will not share

Locations

DE (8)