Last updated: 11/04/2018 13:11:09
This product has been transferred to Novartis. GSK Clinical Study Register is no longer maintained for this study. The most up to date information is available on clinicaltrials.gov.
GW786034 In Subjects With Locally Recurrent Or Metastatic Clear Cell Renal Cell Carcinoma
EudraCT ID
EU CT Number
Not applicable
Trial status
No longer a GSK study
No longer a GSK study
Trial overview
Official title: A Phase II Study of GW786034 Using a Randomised Discontinuation Design in Subjects with Locally Recurrent or Metastatic Clear-Cell Renal Cell Carcinoma
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Single Group Assignment
Masking:
None (Open Label)
Allocation:
Non-randomized
Primary outcomes:
Overall Response by RECIST criteria
Timeframe: Baseline to Response (up to 2.40 years). Assessments occurred at Week 12 and every 8 weeks thereafter.
Stable disease at 12 weeks - Interim Analysis of first 60 participants
Timeframe: Week 12
Secondary outcomes:
Duration of response
Timeframe: First response until progression of disease (up to 2.40 years). Assessments occurred at Week 12 and every 8 weeks thereafter.
Progression-free Survival
Timeframe: From the first day of treatment to the earliest date of disease progression or death due to any cause (up to 2.40 years)
Interventions:
Drug: GW786034
Drug: Placebo
Enrollment:
225
Observational study model:
Not applicable
Primary completion date:
2008-24-03
Time perspective:
Not applicable
Clinical publications:
Bonate PL, Suttle B. Modeling Tumor Growth Kinetics After Treatment With Pazopanib or Placebo in Patients with Renal Cell Carcinoma. Cancer Chemother Pharmacol. 2013;72(1):231-40.
Hutson TE, Davis ID, Machiels JP, De Souza PL, Rottey S, Hong BF, Epstein RJ, Baker KL, McCann L, Crofts T, Liu Y, Pandite L, Figlin R. Efficacy and Safety of Pazopanib (GW786034) in Patients with Metastatic Renal Cell Carcinoma. [J Clin Oncol]. 2010;28(3):475-480.
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;8(August 13):827-37.
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;131(3):e92-4.
Xu CF, Reck BH, Goodman VL, Xue Z, Huang L, Barnes M, Spraggs CF, Mooser VE, Cardon LR, Pandite L. Association of the Hemochromatosis Gene With Pazopanib-Induced Transaminase Elevation in Renal Cell Carcinoma. [J Hepatol]. 2011;54(6):1237-43.
Xu C-f, Reck BH, Xue Z, Huang L, Baker K, Chen M, Chen EP, Ellens HE, Mooser V, Cardon LR, Spraggs C, Pandite L. Pazopanib-induced hyperbilirubinemia is associated with Gilbert’s syndrome UGT1A1 polymorphism. [Br J Cancer]. 2010;102(9):1371-1377.
Choueiri T, Fay AP, Gagnon R, et al. The role of aberrant VHL/HIF pathway elements in predicting clinical outcome to pazopanib therapy in patients with metastatic clear-cell renal cell carcinoma. Clin. Cancer Res. 2013;19(18):5218-26.
Choueiri T, Figueroa D, Fay A, et al.Correlation of PD-L1 Tumor Expression and Treatment Outcomes in Patients with Renal Cell Carcinoma Receiving Sunitinib or Pazopanib: Results from COMPARZ, a Randomized Controlled Trial.Clin Cancer Res.2014;21(5):1071-7
Hutson TE, Davis ID, Machiels JP, et al. Efficacy and Safety of Pazopanib (GW786034) in Patients with Metastatic Renal Cell Carcinoma. J Clin Oncol. 2010;28(3):475-480.
Suttle AB, Ball HA, Molimard M, et al.Relationship Between Exposure to Pazopanib and Efficacy in Patients with Advanced Renal Cell Carcinoma.Br J Cancer.2014;(Oct 28)
Suttle AB, Ball HA, Molimard M, et al.Relationship Between Exposure to Pazopanib and Efficacy in Patients with Advanced Renal Cell Carcinoma.Br J Cancer.2014;111(10):1909-1916
Tran HT, Liu Y, Zurita AJ, et al. 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;13(8):827-37.
Xu C-F, Reck BH, Xue Z, et al. Pazopanib-induced hyperbilirubinemia is associated with Gilbert’s syndrome UGT1A1 polymorphism. Br J Cancer. 2010;102(9):1371-1377.
Xu CF, Reck BH, Goodman VL, et al. Association of the Hemochromatosis Gene With Pazopanib-Induced Transaminase Elevation in Renal Cell Carcinoma. J Hepatol. 2011;54(6):1237-43.
Medical condition
Carcinoma, Renal Cell
Product
pazopanib
Collaborators
Not applicable
Study date(s)
October 2005 to September 2013
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
21+ years
Accepts healthy volunteers
No
- 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
- Received prior non-cytokine or non-bevacizumab therapies .
- Received chemotherapy for renal cell carcinoma.
Inclusion and exclusion 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: a. 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). b. 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.
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.
Trial location(s)
Location
GSK Investigational Site
San Francisco, California, United States, 94115
Status
Study Complete
Location
GSK Investigational Site
Orange, California, United States, 92868
Status
Study Complete
Location
GSK Investigational Site
Aurora, Colorado, United States, 80010
Status
Study Complete
Location
GSK Investigational Site
Duarte, California, United States, 91010-3000
Status
Study Complete
Location
GSK Investigational Site
New York, New York, United States, 10032-3713
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Randwick, New South Wales, Australia, 2031
Status
Study Complete
Location
GSK Investigational Site
East Melbourne, Victoria, Australia, 3002
Status
Study Complete
Location
GSK Investigational Site
Indianapolis, Indiana, United States, 46202
Status
Study Complete
Location
GSK Investigational Site
Kogarah, New South Wales, Australia, 2217
Status
Study Complete
Location
GSK Investigational Site
Camperdown, New South Wales, Australia, 2050
Status
Study Complete
Location
GSK Investigational Site
Nashville, Tennessee, United States, 37203
Status
Study Complete
Location
GSK Investigational Site
Hradec Kralove, Czech Republic, 500 05
Status
Study Complete
Location
GSK Investigational Site
Los Angeles, California, United States, 90095
Status
Study Complete
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
No longer a GSK study
Actual primary completion date
2008-24-03
Actual study completion date
2013-10-09
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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