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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00244764




Registration number
NCT00244764
Ethics application status
Date submitted
25/10/2005
Date registered
27/10/2005
Date last updated
27/03/2017

Titles & IDs
Public title
GW786034 In Subjects With Locally Recurrent Or Metastatic Clear Cell Renal Cell Carcinoma
Scientific title
A Phase II Study of GW786034 Using a Randomised Discontinuation Design in Subjects With Locally Recurrent or Metastatic Clear-Cell Renal Cell Carcinoma
Secondary ID [1] 0 0
VEG102616
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoma, Renal Cell 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GW786034
Treatment: Drugs - Placebo

Experimental: Pazopanib - All patients receive GW786034. At week 12, some subjects will be randomized based on response (SD) and the others will remain on drug. After the interim analysis, the design was changed to an open label, single arm study with all subjects receiving pazopanib.

Placebo comparator: Placebo - All patients receive GW786034. At week 12, some subjects will be randomized based on response (SD) and the others will remain on drug. After the interim analysis, the design was changed to an open label, single arm study with all subjects receiving pazopanib.


Treatment: Drugs: GW786034
All patients receive GW786034. At week 12, some subjects will be randomized based on response (SD) and the others will remain on drug. After the interim analysis, the design was changed to an open label, single arm study with all subjects receiving pazopanib.

Treatment: Drugs: Placebo
All patients receive GW786034. At week 12, some subjects will be randomized based on response (SD) and the others will remain on drug. After the interim analysis, the design was changed to an open label, single arm study with all subjects receiving pazopanib.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Response by RECIST Criteria
Timepoint [1] 0 0
Baseline to Response (up to 2.40 years). Assessments occurred at Week 12 and every 8 weeks thereafter.
Primary outcome [2] 0 0
Stable Disease at 12 Weeks - Interim Analysis of First 60 Participants
Timepoint [2] 0 0
Week 12
Secondary outcome [1] 0 0
Duration of Response
Timepoint [1] 0 0
First response until progression of disease (up to 2.40 years). Assessments occurred at Week 12 and every 8 weeks thereafter.
Secondary outcome [2] 0 0
Progression-free Survival
Timepoint [2] 0 0
From the first day of treatment to the earliest date of disease progression or death due to any cause (up to 2.40 years)

Eligibility
Key inclusion criteria
Inclusion criteria:

* Histologically or cytologically confirmed diagnosis of Renal Cell Carcinoma of predominantly clear-cell histology (excluding chromophobe, papillary, collecting duct, and undifferentiated tumors) which is metastatic or locally recurrent
* Either no prior systemic therapy or failed only 1 prior cytokine-based or bevacizumab-based therapy
* Evidence of documented measurable disease by RECIST criteria
* Male or female at least 21 years of age

A woman is eligible to enter and participate in the study if she is of:

1. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who:

* Has had a hysterectomy,
* Has had a bilateral oophorectomy (ovariectomy),
* Has had a bilateral tubal ligation,
* Is post-menopausal (total cessation of menses for >= 1 year).
2. Childbearing potential, has a negative serum pregnancy test at Screening Period and serum or urine pregnancy test at Day1, 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 follows:

* An intrauterine device (IUD) with a documented failure rate of less than 1% per year.
* Vasectomized partner who is sterile prior to the female subject's entry and is the sole sexual partner for that female.
* Complete abstinence from sexual intercourse for 14 days before exposure to investigation product, through the clinical trial, 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).

A man with a female partner of childbearing potential is eligible to enter and participate in the study if he uses a barrier method of contraception (e.g. condom) or abstinence during the study and for 28 days following the last dose of investigational drug.

* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1.
* Adequate bone marrow function.
* Adequate hepatic function.
* Adequate renal function.
* Adequate PT/PTT or INR/aPTT.
* Able to swallow and retain oral medications.
* Written informed consent.
Minimum age
21 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

* Received prior non-cytokine or non-bevacizumab therapies .
* Received chemotherapy for renal cell carcinoma.
* Have had any major surgery, radiotherapy, or immunotherapy within the last 28 days and/or not recovered from prior therapy.
* History of hypercalcemia within two months of start of therapy.
* Patients who are pregnant or lactating.
* Poorly controlled hypertension.
* QTc prolongation defined as a QTc interval = 480 msecs or other significant ECG abnormalities.
* Has Class II, III or IV heart failure as defined by the New York Heart Association functional classification system. A subject who has a history of Class II heart failure and is asymptomatic on treatment may be considered eligible.
* Any history of cerebrovascular accident [CVA].
* History of myocardial infarction, admission for unstable angina, cardiac angioplasty or stenting within the last 12 weeks.
* History of venous thrombosis in last 12 weeks.
* Current use of therapeutic warfarin.
* Use of antiplatelet agents other than aspirin (= 325 mg/day).
* Leptomeningeal or brain metastases.
* Prior history of malignancies other than renal cell carcinoma (except for basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, or the subject has been free of any other malignancies for > 5 years).
* Any serious and/or unstable pre-existing medical, psychiatric, or other condition (including lab abnormalities) that could interfere with subject safety or obtaining informed consent.
* History of malabsorption syndrome, disease significantly affecting gastrointestinal function or major resection of the stomach or small bowel that could affect absorption, distribution, metabolism or excretion of study drugs. Has any unresolved bowel obstruction or diarrhea.
* Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
* Is on any specifically prohibited medication or requires any of these medications during treatment with GW786034.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/10/2005
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/09/2013
Sample size
Target
Accrual to date
Final
225
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
GSK Investigational Site - Camperdown
Recruitment hospital [2] 0 0
GSK Investigational Site - Kogarah
Recruitment hospital [3] 0 0
GSK Investigational Site - Randwick
Recruitment hospital [4] 0 0
GSK Investigational Site - East Melbourne
Recruitment hospital [5] 0 0
GSK Investigational Site - Footscay
Recruitment hospital [6] 0 0
GSK Investigational Site - Heidelberg
Recruitment hospital [7] 0 0
GSK Investigational Site - Parkville
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2217 - Kogarah
Recruitment postcode(s) [3] 0 0
2031 - Randwick
Recruitment postcode(s) [4] 0 0
3002 - East Melbourne
Recruitment postcode(s) [5] 0 0
3011 - Footscay
Recruitment postcode(s) [6] 0 0
3084 - Heidelberg
Recruitment postcode(s) [7] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Indiana
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
Ohio
Country [7] 0 0
United States of America
State/province [7] 0 0
Tennessee
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
Belgium
State/province [9] 0 0
Bruxelles
Country [10] 0 0
Belgium
State/province [10] 0 0
Gent
Country [11] 0 0
Belgium
State/province [11] 0 0
Jette
Country [12] 0 0
Belgium
State/province [12] 0 0
Liège
Country [13] 0 0
Belgium
State/province [13] 0 0
Roeselare
Country [14] 0 0
Belgium
State/province [14] 0 0
Wilrijk
Country [15] 0 0
China
State/province [15] 0 0
Guangdong
Country [16] 0 0
China
State/province [16] 0 0
Jiangsu
Country [17] 0 0
China
State/province [17] 0 0
Shandong
Country [18] 0 0
China
State/province [18] 0 0
Zhejiang
Country [19] 0 0
China
State/province [19] 0 0
Beijing
Country [20] 0 0
China
State/province [20] 0 0
Shanghai
Country [21] 0 0
Czech Republic
State/province [21] 0 0
Brno
Country [22] 0 0
Czech Republic
State/province [22] 0 0
Hradec Kralove
Country [23] 0 0
Czech Republic
State/province [23] 0 0
Praha 2
Country [24] 0 0
Hong Kong
State/province [24] 0 0
Hong Kong
Country [25] 0 0
Hong Kong
State/province [25] 0 0
Kowloon
Country [26] 0 0
Hong Kong
State/province [26] 0 0
Tuen Mun
Country [27] 0 0
Israel
State/province [27] 0 0
Haifa
Country [28] 0 0
Israel
State/province [28] 0 0
Petach Tikva
Country [29] 0 0
Israel
State/province [29] 0 0
Tel Aviv
Country [30] 0 0
Israel
State/province [30] 0 0
Zrifin
Country [31] 0 0
Taiwan
State/province [31] 0 0
Taipei

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Phase II, multi-center, two-stage study utilising a randomised discontinuation design to evaluate the safety and efficacy of GW786034 (pazopanib) in adult subjects with locally recurrent or metastatic clear-cell Renal Cell Carcinoma (RCC). After the interim analysis, the design was changed to an open label, single arm study with all subjects receiving pazopanib.
Trial website
https://clinicaltrials.gov/study/NCT00244764
Trial related presentations / publications
Bonate PL, Suttle AB. Modeling tumor growth kinetics after treatment with pazopanib or placebo in patients with renal cell carcinoma. Cancer Chemother Pharmacol. 2013 Jul;72(1):231-40. doi: 10.1007/s00280-013-2191-0. Epub 2013 May 29.
Hutson TE, Davis ID, Machiels JP, De Souza PL, Rottey S, Hong BF, Epstein RJ, Baker KL, McCann L, Crofts T, Pandite L, Figlin RA. Efficacy and safety of pazopanib in patients with metastatic renal cell carcinoma. J Clin Oncol. 2010 Jan 20;28(3):475-80. doi: 10.1200/JCO.2008.21.6994. Epub 2009 Dec 14.
Tran HT, Liu Y, Zurita AJ, Lin Y, Baker-Neblett KL, Martin AM, Figlin RA, Hutson TE, Sternberg CN, Amado RG, Pandite LN, Heymach JV. Prognostic or predictive plasma cytokines and angiogenic factors for patients treated with pazopanib for metastatic renal-cell cancer: a retrospective analysis of phase 2 and phase 3 trials. Lancet Oncol. 2012 Aug;13(8):827-37. doi: 10.1016/S1470-2045(12)70241-3. Epub 2012 Jul 2.
White AJ, LaGerche A, Toner GC, Whitbourn RJ. Apical ballooning syndrome during treatment with a vascular endothelial growth factor receptor antagonist. Int J Cardiol. 2009 Jan 24;131(3):e92-4. doi: 10.1016/j.ijcard.2007.07.066. Epub 2007 Oct 24.
Xu CF, Reck BH, Goodman VL, Xue Z, Huang L, Barnes MR, Koshy B, Spraggs CF, Mooser VE, Cardon LR, Pandite LN. Association of the hemochromatosis gene with pazopanib-induced transaminase elevation in renal cell carcinoma. J Hepatol. 2011 Jun;54(6):1237-43. doi: 10.1016/j.jhep.2010.09.028. Epub 2011 Feb 12.
Xu CF, Reck BH, Xue Z, Huang L, Baker KL, Chen M, Chen EP, Ellens HE, Mooser VE, Cardon LR, Spraggs CF, Pandite L. Pazopanib-induced hyperbilirubinemia is associated with Gilbert's syndrome UGT1A1 polymorphism. Br J Cancer. 2010 Apr 27;102(9):1371-7. doi: 10.1038/sj.bjc.6605653. Epub 2010 Apr 13.
Goldstein D, Rosenberg JE, Figlin RA, Townsend RR, McCann L, Carpenter C, Pandite L. Is change in blood pressure a biomarker of pazopanib and sunitinib efficacy in advanced/metastatic renal cell carcinoma? Eur J Cancer. 2016 Jan;53:96-104. doi: 10.1016/j.ejca.2015.10.006. Epub 2015 Dec 15.
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00244764