Letzte Aktualisierung: 18.06.2019

AN 28/09 - PISCES

A randomised double-blind cross-over patient preference study of pazopanib versus sunitinib in treatment naïve locally advanced or metastatic renal cell carcinoma

Status: Planmäßig beendet

ISRCTN EudraCT Clinicaltrials.gov DRKS
2009-014249-10 NCT01064310

Diagnose

  • Nierenzellkarzinom

Studienziel / Fragestellung

Patientenmerkmale

Stadium

Lokal fortgeschritten, metastasiert

Alter

18-100

Ausschlusskriterien

Patients meeting any of the following criteria must not be enrolled in the study:
1. History of another malignancy. Note: Patients who have had another malignancy and have been disease-free for 3 years or patients with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible.
2. History or clinical evidence of central nervous system (CNS) metastases. Note: Patients who have previously-treated CNS metastases (surgery ± radiotherapy,
radiosurgery, or gamma knife) and meet all 3 of the following criteria are eligible:
a. Are asymptomatic and,
b. Have had no evidence of active CNS metastases for ≥6 months prior to enrolment and,
c. Have no requirement for steroids or enzyme-inducing anticonvulsants (EIAC)
3. Clinically significant gastrointestinal abnormalities including, but not limited to:
a. Malabsorption syndrome
b. Major resection of the stomach or small bowel that could affect the absorption of study drug
c. Active peptic ulcer disease
d. Inflammatory bowel disease
e. Ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation
f. History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment.
4. Presence of uncontrolled infection.
5. History of any one or more of the following cardiovascular conditions within the past 12 months:
a. Myocardial infarction
b. Unstable angina
c. Symptomatic peripheral vascular disease
d. Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)
6. History of cerebrovascular accident (CVA) including transient ischemic attack (TIA)
7. History of pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. Note: Patients with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible.
8. Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥155mmHg or diastolic blood pressure (DBP) of ≥ 95mmHg]. Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study
entry. Blood pressure must be re-assessed on two  occasions that are separated by a minimum of 24 hours. The mean SBP/DBP values from each blood pressure assessment must be <150/90mmHg in order for a patient to be eligible for the study.
9. 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.
10. Evidence of active bleeding or bleeding diathesis
11. Significant haemoptysis within 6 weeks of first dose of study drug.
12. Any serious and/or unstable pre-existing medical, psychiatric, or other conditions that could interfere with patient’s safety, obtaining informed consent or compliance to the study.
13. Use any prohibited medications within 14 days of the first dose of study medication.
14. Use of an investigational agent, including an  investi-gational anti-cancer agent, within 28 days or 5 half-lives, whichever is longer, prior to the first dose of study drug.
15. Is now undergoing and/or has undergone in the 14 days immediately prior to first dose of study drug, any cancer therapy (surgery, tumour embolisation, chemotherapy, radiation therapy, immunotherapy, biological therapy, or hormonal therapy)
16. Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is progressing in severity.
17. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib or sunitinib.

Einschlusskriterien

Patients eligible for enrolment in the study must meet all of the following criteria:
1. Patients must provide written informed consent prior to performance of any study-specific procedures or assessments, and must be willing to comply with treatment and follow up. Procedures conducted as part of the patient’s routine clinical management (e.g. blood count,
imaging study) and obtained prior to signing of informed consent may be utilised for screening or baseline purposes provided these procedures are conducted as specified in the protocol.
2. Diagnosis of renal cell carcinoma with clear-cell component histology.
3. Received no prior systemic therapy (interleukin-2, interferon-α, chemotherapy, bevacizumab, mTOR inhibitor, sunitinib, sorafenib or other VEGF TKI) for advanced or metastatic RCC.
4. Locally advanced (defined as disease not amenable to curative surgery or radiation therapy) or metastatic RCC (equivalent to Stage IV RCC according to AJCC staging).
5. ECOG PS of 0 or 1
6. Age ≥ 18 years old
7. A female is eligible to enter and participate in this study if she is of: Non-childbearing potential (i.e., physiologically incapable of becoming pregnant) Childbearing potential, including any female who has had a negative serum pregnancy test within 2 weeks prior to the first dose of study treatment, preferably as close to the first dose as
possible, and agrees to use adequate contraception. GSK acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follow:
• An intrauterine device.
• Vasectomised partner who is sterile prior to the female patient’s entry and is the sole sexual partner for that female.
• Complete abstinence from sexual intercourse for 14 days before exposure to investigational product, through the dosing period, and for at least 21 days after the last
dose of investigational product.
• Double-barrier contraception (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide; or male condom and diaphragm with spermicide).
Note: Oral contraceptives are not reliable due to potential drug-drug interactions. Female patients 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. A male with a female partner of childbearing potential is eligible to enter and participate in the
study if he uses a barrier method of contraception or abstinence during the study.
8. Adequate organ system functions as defined in Table 1.
Table 1 Definitions for Adequate Organ Function

System Laboratory Values

Haematologic
Absolute neutrophil count (ANC) ≥1.5 X 109/L
Haemoglobin1 ≥9 g/dL
Platelets ≥100 X 109/L
International normalized ratio (INR) ≤1.2 X upper limit of normal (ULN)
Partial thromboplastin time (PTT) ≤1.2 X ULN

Hepatic
Total bilirubin ≤1.5 X ULN
AST and ALT ≤2.5 X ULN

Renal
Calculated creatinine clearance ≥30 mL/min
1. Patients may not have had a transfusion within 7 days of screening assessment.
9. Total serum calcium concentration <12.0mg/dL
10. Left ventricular ejection fraction (LVEF) ≥lower limit of institutional normal (LLN) as assessed by echocardio-graphy (ECHO) or multigated acquisition (MUGA) scan. The same modality used at baseline must be applied for subsequent evaluations. French patients: In France, a patient will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Studiendesign

  • Cross-over
  • Doppelblind
  • Multizentrisch
  • Phase III
  • Prospektiv
  • Randomisiert
  • Zweiarmig

Intervention

Dokumente (passwortgeschützt)

Zuständigkeiten Gesamtstudie

Sponsor

  • Novartis Pharma GmbH

Prüfzentrum 1

 

  • Universitätsklinikum Bonn

Studienbüro

  • Klinisches Studienzentrum Urologie

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