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

Carcinoma, Renal Cell Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00244764
• Other study ID #: VEG102616
• Status: Completed
• Phase: Phase 2
• First received: October 25, 2005
• Last updated: September 24, 2015
• Start date: October 2005
• Est. completion date: September 2013

Study information

• Verified date: August 2014
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: Czech Republic: Státní ústav pro kontrolu léciv, Oddelení klinického hodnoceníEuropean Union: European Medicines AgencyBelgium: Agence Fédérale des Médicaments et des Produits de la SantéMalaysia: Ministry of HealthTaiwan: Department of HealthAustralia: Department of Health and Ageing Therapeutic Goods AdministrationChina: Food and Drug AdministrationUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 225
• Est. completion date: September 2013
• Est. primary completion date: March 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell

Intervention

Drug:
• 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.
• 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.

Locations

Country	Name	City	State
Australia	GSK Investigational Site	Camperdown	New South Wales
Australia	GSK Investigational Site	East Melbourne	Victoria
Australia	GSK Investigational Site	Footscay	Victoria
Australia	GSK Investigational Site	Heidelberg	Victoria
Australia	GSK Investigational Site	Kogarah	New South Wales
Australia	GSK Investigational Site	Parkville	Victoria
Australia	GSK Investigational Site	Randwick	New South Wales
Belgium	GSK Investigational Site	Bruxelles
Belgium	GSK Investigational Site	Bruxelles
Belgium	GSK Investigational Site	Gent
Belgium	GSK Investigational Site	Jette
Belgium	GSK Investigational Site	Liège
Belgium	GSK Investigational Site	Roeselare
Belgium	GSK Investigational Site	Wilrijk
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Guangzhou	Guangdong
China	GSK Investigational Site	Hangzhou	Zhejiang
China	GSK Investigational Site	Jinan	Shandong
China	GSK Investigational Site	Nanjing	Jiangsu
China	GSK Investigational Site	Shanghai
Czech Republic	GSK Investigational Site	Brno
Czech Republic	GSK Investigational Site	Hradec Kralove
Czech Republic	GSK Investigational Site	Praha 2
Hong Kong	GSK Investigational Site	Hong Kong
Hong Kong	GSK Investigational Site	Kowloon
Hong Kong	GSK Investigational Site	Tuen Mun
Israel	GSK Investigational Site	Haifa
Israel	GSK Investigational Site	Petach Tikva
Israel	GSK Investigational Site	Tel Aviv
Israel	GSK Investigational Site	Zrifin
Taiwan	GSK Investigational Site	Taipei
Taiwan	GSK Investigational Site	Taipei
United States	GSK Investigational Site	Aurora	Colorado
United States	GSK Investigational Site	Cleveland	Ohio
United States	GSK Investigational Site	Cleveland	Ohio
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Duarte	California
United States	GSK Investigational Site	Indianapolis	Indiana
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Nashville	Tennessee
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	Orange	California
United States	GSK Investigational Site	San Francisco	California
United States	GSK Investigational Site	Tucker	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  China,  Czech Republic,  Hong Kong,  Israel,  Taiwan, 

References & Publications (6)

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. — View Citation

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. — View Citation

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. — View Citation

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. Epub 2007 Oct 24. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response by RECIST Criteria	The overall response is the number of participants who experience a confirmed complete (CR) or partial response (PR) of the total analysis population. Per the Response Evaluation Criteria In Solid Tumors (RECIST): CR = all detectable tumor has disappeared, PR = a >=30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum, Progressive disease (PD) = a >=20% increase in target lesions, Stable Disease = small changes that do not meet previously given criteria.	Baseline to Response (up to 2.40 years). Assessments occurred at Week 12 and every 8 weeks thereafter.	No
Primary	Stable Disease at 12 Weeks - Interim Analysis of First 60 Participants	The protocol called for an interim analysis of the first 60 participants to determine their status at Week 12, and to determine the number of participants with stable disease, although all categories were reported. Stable disease is defined as a disease that has not grown enough to be called progressive disease and has not shrunk enough to be called partial/complete response.	Week 12	No
Secondary	Duration of Response	Using RECIST criteria: date of first confirmed tumor response (CR or PR) to date of tumor progression or to death. Participants who did not progress or die were censored at their last radiologic assessment. Only participants who had a response were analyzed.	First response until progression of disease (up to 2.40 years). Assessments occurred at Week 12 and every 8 weeks thereafter.	No
Secondary	Progression-free Survival	Progression-free Survival is defined as the interval between the first day of treatment and the earliest date of disease progression or death due to any cause, whichever occurred first. Progressive disease is defined as a >=20% increase in target lesions.	From the first day of treatment to the earliest date of disease progression or death due to any cause (up to 2.40 years)	No