| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Locally Advanced and/or Metastatic Renal Cell Carcinoma |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10050513 |
| E.1.2 | Term | Metastatic renal cell carcinoma |
|
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To assess how the tolerability and safety differences between pazopanib and sunitinib translate into patient preference. |
|
| E.2.2 | Secondary objectives of the trial |
•To evaluate the reason for patient preference as assessed by a patient preference questionnaire
•To evaluate fatigue as assessed by FACIT-Fatigue and quality of life as assessed by EuroQoL EQ-5D.
•To evaluate dose modifications and time to dose modification
•To evaluate the safety and tolerability (including AEs, SAEs, withdrawal of treatment due to AE, vital signs, ECG and clinical laboratory).
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
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.Received no prior systemic therapy (including interleukin-2, interferon-α, chemotherapy, bevacizumab, mTOR inhibitor, sunitinib, sorafenib or other VEGF TKI) for advanced or metastatic RCC. Patients who received adjuvant treatment with a cancer vaccine are eligible.
3.Locally advanced (defined as disease not amenable to curative surgery or radiation therapy) or metastatic renal cell carcinoma of any histology (equivalent to Stage IV RCC according to AJCC staging). Patients with non-measurable disease are allowed if metastatic disease can be confirmed.
4.ECOG PS of 0 or 1
5.Age ≥18 years
6.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 two weeks prior to the first dose of study treatment, preferably as close to the first dose as possible and agrees to use adequate contraception (A list of GSK acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are given in the appendix 11.4 of the protocol).
7.Adequate organ system functions as defined in Table 2 of the protocol.
8.Total serum calcium concentration <12.0mg/dL
9.Left ventricular ejection fraction (LVEF) ≥lower limit of institutional normal (LLN) as assessed by echocardiography (ECHO) or multigated acquisition (MUGA) scan. The same modality used at baseline must be applied for subsequent evaluations.
10.Patient is able to swallow and retain oral tablets
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 or of a health insurance valid in France.
|
|
| E.4 | Principal exclusion criteria |
1.Poor MSKCC risk group
2.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.
3.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,
b.Have had no evidence of active CNS metastases for ≥6 months prior to enrolment ,
c.Have no requirement for steroids or enzyme-inducing anticonvulsants (EIAC).
4.Any clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding or affect absorption of investigational product 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.
5.Presence of uncontrolled infection.
6.Corrected QT interval (QTc) >480 msecs using Bazett’s formula
7.History of one or more of the following cardiovascular conditions within the past 6 months:
a.Cardiac angioplasty or stenting
b.Myocardial infarction
c.Unstable angina
d.Coronary artery bypass graft surgery
e.Symptomatic peripheral vascular disease
f.Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)
8.Poorly controlled hypertension (defined as systolic blood pressure (SBP) of > 150mmHg or diastolic blood pressure (DBP) of > 90mmHg) at baseline.
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 1 hour within a visit. 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.History of cerebrovascular accident (CVA) including transient ischemic attack (TIA), 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.
10.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 (procedures such as catheter placement not considered to be major).
11.Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels.
12.Evidence of active bleeding or bleeding diathesis.
13.Significant haemoptysis within 6 weeks prior to first dose of study drug.
14.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.
15.Use any prohibited medications within 14 days of the first dose of study medication.
16.Use of an investigational agent, including an investigational anti-cancer agent, within 28 days or 5 half-lives, whichever is longer, prior to the first dose of study drug.
17.Radiation therapy, surgery or tumour embolisation within 14 days prior to the first dose of study treatment.
18.Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib or sunitinib.
19.Pregnant or lactating female
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.
Patients in France: the patient has participated in any study using an investigational drug during the previous 30 days or 5 half-lives of the investigational drug (whichever is longer).
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|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| •Patient preference (pazopanib vs. sunitinib) as assessed by patient preference questionnaire |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | Yes |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 45 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| last subject last visit, as per protocol |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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