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

NCT00244764 | Completed Phase 2 Results DMC

• 1 other identifier: VEG102616
• Study Type: interventional
• Target: 225
• Locations: 8 countries
• Sites: 45

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.

Conditions

Carcinoma, Renal Cell

Keywords

Angiogenesis; Renal Cell Carcinoma; Solid tumors; Pazopanib(GW786034)

Outcome Measures

Primary Outcomes (2)

• 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.

• 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

Secondary Outcomes (2)

• Duration of Response

  First response until progression of disease (up to 2.40 years). Assessments occurred at Week 12 and every 8 weeks thereafter.

• Progression-free Survival

  From the first day of treatment to the earliest date of disease progression or death due to any cause (up to 2.40 years)

Study Arms (2)

Pazopanib

EXPERIMENTAL

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.

Drug: GW786034

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

GW786034 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.

Pazopanib

Placebo 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

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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).
• 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).

You may not qualify if:

• 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).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (45)

GSK Investigational Site

Duarte, California, 91010-3000, United States

Location

GSK Investigational Site

Los Angeles, California, 90095, United States

Location

GSK Investigational Site

Orange, California, 92868, United States

Location

GSK Investigational Site

San Francisco, California, 94115, United States

Location

GSK Investigational Site

Aurora, Colorado, 80010, United States

Location

GSK Investigational Site

Tucker, Georgia, 30084, United States

Location

GSK Investigational Site

Indianapolis, Indiana, 46202, United States

Location

GSK Investigational Site

New York, New York, 10032-3713, United States

Location

GSK Investigational Site

Cleveland, Ohio, 44106, United States

Location

GSK Investigational Site

Cleveland, Ohio, 44195, United States

Location

GSK Investigational Site

Nashville, Tennessee, 37203, United States

Location

GSK Investigational Site

Dallas, Texas, 75246, United States

Location

GSK Investigational Site

Camperdown, New South Wales, 2050, Australia

Location

GSK Investigational Site

Kogarah, New South Wales, 2217, Australia

Location

GSK Investigational Site

Randwick, New South Wales, 2031, Australia

Location

GSK Investigational Site

East Melbourne, Victoria, 3002, Australia

Location

GSK Investigational Site

Footscay, Victoria, 3011, Australia

Location

GSK Investigational Site

Heidelberg, Victoria, 3084, Australia

Location

GSK Investigational Site

Parkville, Victoria, 3050, Australia

Location

GSK Investigational Site

Brussels, 1070, Belgium

Location

GSK Investigational Site

Brussels, 1200, Belgium

Location

GSK Investigational Site

Ghent, 9000, Belgium

Location

GSK Investigational Site

Jette, 1090, Belgium

Location

GSK Investigational Site

Liège, 4000, Belgium

Location

GSK Investigational Site

Roeselare, 8800, Belgium

Location

GSK Investigational Site

Wilrijk, 2610, Belgium

Location

GSK Investigational Site

Guangzhou, Guangdong, 510060, China

Location

GSK Investigational Site

Nanjing, Jiangsu, 210029, China

Location

GSK Investigational Site

Jinan, Shandong, 250012, China

Location

GSK Investigational Site

Hangzhou, Zhejiang, 310003, China

Location

GSK Investigational Site

Beijing, 100034, China

Location

GSK Investigational Site

Beijing, 100853, China

Location

GSK Investigational Site

Shanghai, 200040, China

Location

GSK Investigational Site

Brno, 656 53, Czechia

Location

GSK Investigational Site

Hradec Králové, 500 05, Czechia

Location

GSK Investigational Site

Prague, 12808, Czechia

Location

GSK Investigational Site

Hong Kong, Hong Kong

Location

GSK Investigational Site

Kowloon, Hong Kong

Location

GSK Investigational Site

Tuenmen, Hong Kong

Location

GSK Investigational Site

Haifa, 31096, Israel

Location

GSK Investigational Site

Petah Tikva, 49100, Israel

Location

GSK Investigational Site

Tel Aviv, 64239, Israel

Location

GSK Investigational Site

Zrifin, 70300, Israel

Location

GSK Investigational Site

Taipei, 100, Taiwan

Location

GSK Investigational Site

Taipei, Taiwan

Location

Related Publications (7)

• 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.

  PMID: 23715625 BACKGROUND

• 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.

  PMID: 20008644 BACKGROUND

• 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.

  PMID: 22759480 BACKGROUND

• 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.

  PMID: 17920711 BACKGROUND

• 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.

  PMID: 21145803 BACKGROUND

• 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.

  PMID: 20389299 BACKGROUND

• 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.

  PMID: 26702763 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

pazopanib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2005
• First Posted: October 27, 2005
• Study Start: October 1, 2005
• Primary Completion: March 1, 2008
• Study Completion: September 1, 2013
• Last Updated: March 27, 2017
• Results First Posted: January 25, 2011

Record last verified: 2015-09

Locations

IL (4); US (12); TW (2); CN (7); BE (7); AU (7); HK (3); CZ (3)