Patient Preference Study of Pazopanib Versus Sunitinib in Advanced or Metastatic Kidney Cancer

NCT01064310 | Completed Phase 3 Results

• 1 other identifier: 113046
• Study Type: interventional
• Target: 169
• Locations: 5 countries
• Sites: 51

Brief Summary

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.

Conditions

Carcinoma, Renal Cell

Keywords

renal cell carcinoma; Votrient; cancer; pazopanib; patient preference; quality of life

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Preference for Pazopanib Versus Sunitinib as Assessed by the Patient Preference Questionnaire (PPQ)

  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.

  End of treatment of both study drugs (maximum of 22 weeks)

• 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

  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.

  End of treatment of both study drugs (maximum of 22 weeks)

Secondary Outcomes (9)

• 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])

• 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])

• 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)

• Number of Participants With the Indicated Reason for Receiving a Dose Reduction

  End of second treatment period (maximum of 22 weeks)

Study Arms (2)

pazopanib followed by sunitinib

EXPERIMENTAL

800mg pazopanib orally for 10 weeks followed by 50mg sunitinib orally for 10 weeks

Drug: pazopanib; Drug: sunitinib

sunitinib followed by pazopanib

EXPERIMENTAL

50mg sunitinib orally for 10 weeks followed by 800mg pazopanib orally for 10 weeks

Drug: pazopanib; Drug: sunitinib

Interventions

pazopanib DRUG

oral anti-angiogenic treatment

Also known as: Votrient

pazopanib followed by sunitinib; sunitinib followed by pazopanib

sunitinib DRUG

oral anti-angiogenic treatment

Also known as: Sutent

pazopanib followed by sunitinib; sunitinib followed by pazopanib

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (51)

Novartis Investigative Site

Helsinki, 00029, Finland

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Novartis Investigative Site

Joensuu, 80210, Finland

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Novartis Investigative Site

Lahti, 15850, Finland

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Novartis Investigative Site

Seinäjoki, 60220, Finland

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Novartis Investigative Site

Turku, 20520, Finland

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Novartis Investigative Site

Vaasa, 65130, Finland

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Novartis Investigative Site

Angers, 49933, France

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Novartis Investigative Site

Bordeaux, 33075, France

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Novartis Investigative Site

Caen, 14076, France

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Novartis Investigative Site

Colmar, 68024, France

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Novartis Investigative Site

Hyères, 83400, France

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Novartis Investigative Site

Lille, 59020, France

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Novartis Investigative Site

Lyon, 69373, France

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Novartis Investigative Site

Marseille, 13273, France

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Novartis Investigative Site

Paris, 75908, France

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Novartis Investigative Site

Rennes, 35042, France

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Novartis Investigative Site

Rouen, 76031, France

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Novartis Investigative Site

Saint-Priest-en-Jarez, 42271, France

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Novartis Investigative Site

Strasbourg, 67085, France

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Novartis Investigative Site

Strasbourg, 67091, France

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Novartis Investigative Site

Villejuif, 94805, France

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Novartis Investigative Site

Ravensburg, Baden-Wurttemberg, 88212, Germany

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Novartis Investigative Site

Fürth, Bavaria, 90766, Germany

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Novartis Investigative Site

Munich, Bavaria, 81675, Germany

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Novartis Investigative Site

Goslar, Lower Saxony, 38642, Germany

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Novartis Investigative Site

Aachen, North Rhine-Westphalia, 52074, Germany

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Novartis Investigative Site

Bonn, North Rhine-Westphalia, 53127, Germany

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Novartis Investigative Site

Neuss, North Rhine-Westphalia, 41462, Germany

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Novartis Investigative Site

Mainz, Rhineland-Palatinate, 55131, Germany

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Novartis Investigative Site

Berlin, State of Berlin, 10117, Germany

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Novartis Investigative Site

Lecce, Apulia, 73100, Italy

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Novartis Investigative Site

Meldola (FC), Emilia-Romagna, 47014, Italy

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Novartis Investigative Site

Aviano (PN), Friuli Venezia Giulia, 33081, Italy

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Novartis Investigative Site

Rome, Lazio, 00152, Italy

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Novartis Investigative Site

Bergamo, Lombardy, 24128, Italy

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Novartis Investigative Site

Monza, Lombardy, 20052, Italy

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Novartis Investigative Site

Pavia, Lombardy, 27100, Italy

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Novartis Investigative Site

Taormina, Sicily, Italy

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Novartis Investigative Site

Lido Di Camaiore (LU), Tuscany, 55043, Italy

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Novartis Investigative Site

Pisa, Tuscany, 56126, Italy

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Novartis Investigative Site

Chieti, 66100, Italy

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Novartis Investigative Site

Birmingham, B9 5SS, United Kingdom

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Novartis Investigative Site

Bournemouth, BH7 7DW, United Kingdom

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Novartis Investigative Site

Cottingham, HU16 5JQ, United Kingdom

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Novartis Investigative Site

Manchester, M20 4BX, United Kingdom

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Novartis Investigative Site

Newcastle upon Tyne, NE7 7DN, United Kingdom

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Novartis Investigative Site

Norwich, NR4 7UY, United Kingdom

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Novartis Investigative Site

Plymouth, PL6 8DH, United Kingdom

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Novartis Investigative Site

Preston, PR2 9HT, United Kingdom

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Novartis Investigative Site

Shrewsbury, SY3 8XQ, United Kingdom

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Novartis Investigative Site

Wolverhampton, WV10 0QP, United Kingdom

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Related Publications (4)

• Aldin A, Besiroglu B, Adams A, Monsef I, Piechotta V, Tomlinson E, Hornbach C, Dressen N, Goldkuhle M, Maisch P, Dahm P, Heidenreich A, Skoetz N. First-line therapy for adults with advanced renal cell carcinoma: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2023 May 4;5(5):CD013798. doi: 10.1002/14651858.CD013798.pub2.

  PMID: 37146227 DERIVED

• Oudard S, Benhamouda N, Escudier B, Ravel P, Tran T, Levionnois E, Negrier S, Barthelemy P, Berdah JF, Gross-Goupil M, Sternberg CN, Bono P, Porta C, De Giorgi U, Parikh O, Hawkins R, Highley M, Wilke J, Decker T, Tanchot C, Gey A, Terme M, Tartour E. Decrease of Pro-Angiogenic Monocytes Predicts Clinical Response to Anti-Angiogenic Treatment in Patients with Metastatic Renal Cell Carcinoma. Cells. 2021 Dec 22;11(1):17. doi: 10.3390/cells11010017.

  PMID: 35011579 DERIVED

• Lai JS, Beaumont JL, Diaz J, Khan S, Cella D. Validation of a short questionnaire to measure symptoms and functional limitations associated with hand-foot syndrome and mucositis in patients with metastatic renal cell carcinoma. Cancer. 2016 Jan 15;122(2):287-95. doi: 10.1002/cncr.29655. Epub 2015 Oct 12.

  PMID: 26457466 DERIVED

• Escudier B, Porta C, Bono P, Powles T, Eisen T, Sternberg CN, Gschwend JE, De Giorgi U, Parikh O, Hawkins R, Sevin E, Negrier S, Khan S, Diaz J, Redhu S, Mehmud F, Cella D. Randomized, controlled, double-blind, cross-over trial assessing treatment preference for pazopanib versus sunitinib in patients with metastatic renal cell carcinoma: PISCES Study. J Clin Oncol. 2014 May 10;32(14):1412-8. doi: 10.1200/JCO.2013.50.8267. Epub 2014 Mar 31.

  PMID: 24687826 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell; Neoplasms; Patient Preference

Interventions

pazopanib; Sunitinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; 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; Patient Satisfaction; Treatment Adherence and Compliance; Health Behavior; Behavior

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

The study remained open to allow subjects currently on treatment continued access to treatment with open label pazopanib.

Results Point of Contact

• Title: Clinical Disclosure Office
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2010
• First Posted: February 8, 2010
• Study Start: May 17, 2010
• Primary Completion: October 19, 2011
• Study Completion: November 23, 2015
• Last Updated: April 17, 2017
• Results First Posted: August 23, 2012

Record last verified: 2017-03

Locations

GB (10); FR (15); DE (9); FI (6); IT (11)