A Randomised Double-blind Cross-over Patient Preference Study of Pazopanib Versus Sunitinib in Treatment naïve Locally Advanced or Metastatic Renal Cell Carcinoma.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 169
- 试验地点
- 1
- 主要终点
- Number of Participants With Preference for Pazopanib Versus Sunitinib as Assessed by the Patient Preference Questionnaire (PPQ)
研究概览
简要总结
This is a randomised, double-blind, cross-over study of pazopanib versus sunitinib in patients with locally advanced or metastatic renal cell carcinoma (mRCC) who have received no prior systemic therapy for advanced or metastatic RCC. Approximately 160 eligible patients will be stratified based on the ECOG performance status (0 vs. 1) and number of metastatic sites of disease (0 and 1 vs. >=2). The study consists of two treatment periods of 10 weeks with a 2-week wash-out period between the two treatment periods. Patients will receive pazopanib and sunitinib treatment sequentially in a double-blinded fashion. The primary objective of the study is to assess how the tolerability and safety differences between pazopanib and sunitinib translate into patient preference, defined by the patient's stated preference for which drug they may prefer to continue treatment with at end of study. The secondary objectives are 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; and to evaluate safety.
详细描述
This is a randomised, double-blind, cross-over study to evaluate the patient preference of pazopanib versus sunitinib in patients with locally advanced or metastatic RCC who have received no prior systemic therapy for advanced or metastatic RCC. Approximately 160 eligible patients will be stratified based on the ECOG performance status (0 vs. 1) and number of metastatic sites of disease (0 and 1 vs. 2+).
The study consists of two 10-weeks treatment periods with a two-week wash-out period between the treatment periods. Patients will receive pazopanib and sunitinib treatment sequentially. At the end of the second treatment period, patient preference and disease assessment are evaluated and the patients are unblinded. Further treatment is at the discretion of the physician. Further treatment with pazopanib is available within the study. Patients requiring other treatments will complete the study at this point.
Patients will be randomized in a 1:1 ratio to receive blinded (overencapsulated) study drug: either 800mg pazopanib orally for 10 weeks followed by 50mg sunitinib orally for 10 weeks or 50mg sunitinib orally for 10 weeks followed by 800mg pazopanib orally for 10 weeks. A two-week washout period will separate the treatment periods (the medical monitor should be consulted if ongoing AEs need to be resolved and the wash-out period needs to be extended). The regimen for sunitinib is 4 weeks of treatment followed by 2 weeks off treatment. To maintain the double-blind during the two weeks off drug for patients on sunitinib ('Treatment Holiday'), patients will be taking matching placebo. No study drug will be taken during the wash-out period in either arm.
Following the two-week wash-out period and disease assessment, all patients are planned to cross over to the second treatment. Patients will be informed of their disease assessment result and any patient that wishes to come off study at this point due to a very significant response, defined as more than a 50% reduction in tumour size (or complete response if non-measurable disease), will have the option to be unblinded to continue with whichever treatment they were on, however each patient case will need to be discussed with the medical monitor prior to unblinding. Patients who were on sunitinib will leave the study and continue treatment outside the study. Patients who were on pazopanib will continue on pazopanib within the pazopanib open-label part of the study. Conversely, should a patient have a very significant response and wish to cross over or complete the study, this must be documented in the patients notes.
Patients crossing over with progressive disease will follow the same visit schedule and assessments and investigators will have the option for these patients to be unblinded or not. The patients' preference will be collected and analysed but will not contribute to the primary, but an exploratory analysis because of the bias caused by progressing on the first treatment. Even if unblinded, patients may continue to receive the second treatment and may receive open label pazopanib after the second treatment within the study if they did not progress on pazopanib.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •Received no prior systemic therapy (including interleukin-2, interferon-alpha, 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.
- •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.
- •ECOG PS of 0 or 1
- •Age >= 18 years
- •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.
- •Adequate organ system functions
- •Total serum calcium concentration <12.0mg/dL
- •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.
- •Patient is able to swallow and retain oral tablets
排除标准
- •Poor MSKCC risk group
- •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.
- •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:
- •Are asymptomatic,
- •Have had no evidence of active CNS metastases for >=6 months prior to enrolment ,
- •Have no requirement for steroids or enzyme-inducing anticonvulsants (EIAC).
- •Any clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding or affect absorption of investigational product including, but not limited to:
- •Malabsorption syndrome
- •Major resection of the stomach or small bowel that could affect the absorption of study drug
- •Active peptic ulcer disease
- •Inflammatory bowel disease
- •Ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation
- •History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment.
- •Presence of uncontrolled infection.
- •Corrected QT interval (QTc) >480 msecs using Bazett's formula
- •History of one or more of the following cardiovascular conditions within the past 6 months:
- •Cardiac angioplasty or stenting
- •Myocardial infarction
- •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 (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.
- •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.
- •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).
- •Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels.
- •Evidence of active bleeding or bleeding diathesis.
- •Significant haemoptysis within 6 weeks prior to first dose of study drug.
- •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.
- •Use any prohibited medications within 14 days of the first dose of study medication.
- •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.
- •Radiation therapy, surgery or tumour embolisation within 14 days prior to the first dose of study treatment.
- •Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib or sunitinib.
- •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.
研究组 & 干预措施
sunitinib followed by pazopanib
50mg sunitinib orally for 10 weeks followed by 800mg pazopanib orally for 10 weeks
干预措施: sunitinib (Drug)
pazopanib followed by sunitinib
800mg pazopanib orally for 10 weeks followed by 50mg sunitinib orally for 10 weeks
干预措施: pazopanib (Drug)
pazopanib followed by sunitinib
800mg pazopanib orally for 10 weeks followed by 50mg sunitinib orally for 10 weeks
干预措施: sunitinib (Drug)
sunitinib followed by pazopanib
50mg sunitinib orally for 10 weeks followed by 800mg pazopanib orally for 10 weeks
干预措施: pazopanib (Drug)
结局指标
主要结局
Number of Participants With Preference for Pazopanib Versus Sunitinib as Assessed by the Patient Preference Questionnaire (PPQ)
时间窗: End of treatment of both study drugs (maximum of 22 weeks)
The PPQ is used to measure participants' preference for pazopanib or sunitinib for renal cell carcinoma management and is used to determine a participant's preference for 1 of the 2 drugs given in the 2 double-blind treatment periods. Participants were asked to select 1 of the following: 1. prefer the drug taken as the first treatment; 2. prefer the drug taken as the second treatment; or 3, no preference. Those participants who indicated a preference were asked to select the factors that had an influence on their treatment preference, as well as the most important reason for their preference.
Number of Participants Answering "Yes," "no," or Not Applicable (N/A) to the Question of Whether the Indicated Factors Influenced Their Preference for Sunitinib or Pazopanib Treatment as Assessed by the Patient Preference Questionnaire
时间窗: End of treatment of both study drugs (maximum of 22 weeks)
The PPQ is used to measure participants' preference for pazopanib or sunitinib for renal cell carcinoma management and is used to determine a participant's preference for 1 of the 2 drugs given in the 2 double-blind treatment periods. Participants were asked to select 1 of the following: 1. prefer the drug taken as the first treatment; 2. prefer the drug taken as the second treatment; or 3, no preference. Those participants who indicated a preference were asked to select the factors that had an influence on their treatment preference, as well as the most important reason for their preference.
次要结局
- Number of Participants With the Indicated AEs Leading to Permanent Discontinuation of Study Treatment(Baseline to end of study (maximum of 22 weeks))
- Change From Baseline (BL) in Systolic Blood Pressure (SBP) and Diastolic BP (DBP)(Baseline of Period (P) 1 (Screening); Period 1 Weeks 2 and 6 (Study Weeks 2 and 6); Baseline of Period 2 (Washout=Study Week 12); Period 2 Weeks 2, 6, and 10 (Study Weeks 14, 18, and 22))
- Number of Participants With Grade 1 to Grade 5 Adverse Events (AEs)(Baseline to end of study (maximum of 22 weeks))
- Quality of Life as Assessed by the EuroQoL-5 Dimensions (EQ-5D) Thermometer and Utility Scores(Day 1 (Period 1 Pre-dose); during 2-week Wash-out Period (Study Weeks 11 and 12); and End of Study (Week 10 of Period 2 [Study Week 22]))
- Number of Participants With the Indicated Reason for Receiving a Dose Reduction(End of second treatment period (maximum of 22 weeks))
- Change From Period Baseline (BL) in Fatigue as Assessed by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score(Day 1 (Period [P] 1 Pre-dose); Weeks 2, 4, 6, 8, and 10 of P 1; during 2-week Wash-out Period (Study Weeks 11 and 12); Weeks 2, 4, 6, and 8 of P 2 (Study Weeks 14, 16, 18, 20, and 22, respectively); End of Study (Week 10 of P 2 [Study Week 22]))
- Time to Dose Modification(End of second treatment period (maximum of 22 weeks))
- Number of Participants With the Indicated Number of Dose Reductions(End of second treatment period (maximum of 22 weeks))
- Change From Baseline (BL) in Heart Rate(Baseline of Period (P) 1 (Screening); Period 1 Weeks 2 and 6 (Study Weeks 2 and 6); Baseline of Period 2 (Washout=Study Week 12); Period 2 Weeks 2, 6, and 10 (Study Weeks 14, 18, and 22))