GW786034 In Subjects With Locally Recurrent Or Metastatic Clear Cell Renal Cell Carcinoma

NCT ID: NCT00244764

Last Updated: 2017-03-27

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

225 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-10-31

Study Completion Date

2013-09-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Carcinoma, Renal Cell

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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.

Group Type EXPERIMENTAL

GW786034

Intervention Type DRUG

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

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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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.

Intervention Type DRUG

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 Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.

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.
Minimum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

GlaxoSmithKline

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

GSK Investigational Site

Duarte, California, United States

Site Status

GSK Investigational Site

Los Angeles, California, United States

Site Status

GSK Investigational Site

Orange, California, United States

Site Status

GSK Investigational Site

San Francisco, California, United States

Site Status

GSK Investigational Site

Aurora, Colorado, United States

Site Status

GSK Investigational Site

Tucker, Georgia, United States

Site Status

GSK Investigational Site

Indianapolis, Indiana, United States

Site Status

GSK Investigational Site

New York, New York, United States

Site Status

GSK Investigational Site

Cleveland, Ohio, United States

Site Status

GSK Investigational Site

Cleveland, Ohio, United States

Site Status

GSK Investigational Site

Nashville, Tennessee, United States

Site Status

GSK Investigational Site

Dallas, Texas, United States

Site Status

GSK Investigational Site

Camperdown, New South Wales, Australia

Site Status

GSK Investigational Site

Kogarah, New South Wales, Australia

Site Status

GSK Investigational Site

Randwick, New South Wales, Australia

Site Status

GSK Investigational Site

East Melbourne, Victoria, Australia

Site Status

GSK Investigational Site

Footscay, Victoria, Australia

Site Status

GSK Investigational Site

Heidelberg, Victoria, Australia

Site Status

GSK Investigational Site

Parkville, Victoria, Australia

Site Status

GSK Investigational Site

Brussels, , Belgium

Site Status

GSK Investigational Site

Brussels, , Belgium

Site Status

GSK Investigational Site

Ghent, , Belgium

Site Status

GSK Investigational Site

Jette, , Belgium

Site Status

GSK Investigational Site

Liège, , Belgium

Site Status

GSK Investigational Site

Roeselare, , Belgium

Site Status

GSK Investigational Site

Wilrijk, , Belgium

Site Status

GSK Investigational Site

Guangzhou, Guangdong, China

Site Status

GSK Investigational Site

Nanjing, Jiangsu, China

Site Status

GSK Investigational Site

Jinan, Shandong, China

Site Status

GSK Investigational Site

Hangzhou, Zhejiang, China

Site Status

GSK Investigational Site

Beijing, , China

Site Status

GSK Investigational Site

Beijing, , China

Site Status

GSK Investigational Site

Shanghai, , China

Site Status

GSK Investigational Site

Brno, , Czechia

Site Status

GSK Investigational Site

Hradec Králové, , Czechia

Site Status

GSK Investigational Site

Prague, , Czechia

Site Status

GSK Investigational Site

Hong Kong, , Hong Kong

Site Status

GSK Investigational Site

Kowloon, , Hong Kong

Site Status

GSK Investigational Site

Tuenmen, , Hong Kong

Site Status

GSK Investigational Site

Haifa, , Israel

Site Status

GSK Investigational Site

Petah Tikva, , Israel

Site Status

GSK Investigational Site

Tel Aviv, , Israel

Site Status

GSK Investigational Site

Zrifin, , Israel

Site Status

GSK Investigational Site

Taipei, , Taiwan

Site Status

GSK Investigational Site

Taipei, , Taiwan

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States Australia Belgium China Czechia Hong Kong Israel Taiwan

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 23715625 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20008644 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22759480 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17920711 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21145803 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20389299 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26702763 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

VEG102616

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.