Clinical trial NCT00244764: GW786034 In Subjects With Locally Recurrent Or Metastatic Clear Cell Renal Cell Carcinoma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carcinoma, Renal Cell
Keywords: Angiogenesis
Renal Cell Carcinoma
Solid tumors
Pazopanib(GW786034)
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2005-10-27
Enrollment: 225
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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.

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.

Primary outcomes:
measure: Overall Response by RECIST Criteria
timeFrame: Baseline to Response (up to 2.40 years). Assessments occurred at Week 12 and every 8 weeks thereafter.
measure: Stable Disease at 12 Weeks - Interim Analysis of First 60 Participants
timeFrame: Week 12
Secondary outcomes:
measure: 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.
measure: 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)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: GSK Investigational Site
state: California
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Orange
country: United States
facility: GSK Investigational Site
state: California
city: San Francisco
country: United States
facility: GSK Investigational Site
state: California
city: Aurora
country: United States
facility: GSK Investigational Site
state: Colorado
city: Tucker
country: United States
facility: GSK Investigational Site
state: Georgia
city: Indianapolis
country: United States
facility: GSK Investigational Site
state: Indiana
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Cleveland
country: United States
facility: GSK Investigational Site
state: Ohio
city: Cleveland
country: United States
facility: GSK Investigational Site
state: Ohio
city: Nashville
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Camperdown
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Kogarah
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Randwick
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: East Melbourne
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Footscay
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Heidelberg
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Parkville
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Bruxelles
country: Belgium
facility: GSK Investigational Site
city: Bruxelles
country: Belgium
facility: GSK Investigational Site
city: Gent
country: Belgium
facility: GSK Investigational Site
city: Jette
country: Belgium
facility: GSK Investigational Site
city: Liège
country: Belgium
facility: GSK Investigational Site
city: Roeselare
country: Belgium
facility: GSK Investigational Site
city: Wilrijk
country: Belgium
facility: GSK Investigational Site
city: Guangzhou
country: China
facility: GSK Investigational Site
state: Guangdong
city: Nanjing
country: China
facility: GSK Investigational Site
state: Jiangsu
city: Jinan
country: China
facility: GSK Investigational Site
state: Shandong
city: Hangzhou
country: China
facility: GSK Investigational Site
state: Zhejiang
city: Beijing
country: China
facility: GSK Investigational Site
city: Beijing
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
city: Brno
country: Czech Republic
facility: GSK Investigational Site
city: Hradec Kralove
country: Czech Republic
facility: GSK Investigational Site
city: Praha 2
country: Czech Republic
facility: GSK Investigational Site
city: Hong Kong
country: Hong Kong
facility: GSK Investigational Site
city: Kowloon
country: Hong Kong
facility: GSK Investigational Site
city: Tuen Mun
country: Hong Kong
facility: GSK Investigational Site
city: Haifa
country: Israel
facility: GSK Investigational Site
city: Petach Tikva
country: Israel
facility: GSK Investigational Site
city: Tel Aviv
country: Israel
facility: GSK Investigational Site
city: Zrifin
country: Israel
facility: GSK Investigational Site
city: Taipei
country: Taiwan
facility: GSK Investigational Site
city: Taipei
country: Taiwan
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
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.
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.
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. doi: 10.1016/j.ijcard.2007.07.066. Epub 2007 Oct 24.
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.
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.
citation: 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.