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Everolimus Post Pazopanib Treatment in Metastatic or Advanced Renal Cell Carcinoma (CATChEz)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01545817
First received: November 17, 2011
Last updated: January 23, 2014
Last verified: January 2014

November 17, 2011
January 23, 2014
April 2012
September 2015   (final data collection date for primary outcome measure)
Median progression free survival on everolimus [ Time Frame: Everolimus treatment until earliest date of disease progression or death, assessed up to 30 months after the last patient has been enrolled ] [ Designated as safety issue: No ]
Median progression free survival on everolimus as second line treatment post pazopanib as first line
Median progression free survival on everolimus [ Time Frame: Everolimus treatment until earliest date of disease progression or death, assessed up to 30 months ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01545817 on ClinicalTrials.gov Archive Site
  • Progression free survival proportion at three and six months after first everolimus dose [ Time Frame: Initiation of everolimus treatment until earliest date of disease progression or death, assessed at three and six months after first everolimus dose ] [ Designated as safety issue: No ]
  • Objective Response Rate to everolimus therapy [ Time Frame: Initiation of everolimus treatment until time of confirmed best response, assessed up to 30 months after the last patient has been enrolled ] [ Designated as safety issue: No ]
  • Objective response rate to pazopanib therapy [ Time Frame: Initiation of pazopanib treatment until time of confirmed best response, assessed up to 30 months after the last patient has been enrolled ] [ Designated as safety issue: No ]
  • Overall survival of patients treated with second-line everolimus therapy [ Time Frame: Initiation of everolimus dose until death, assessed up to 30 months after the last patient has been enrolled ] [ Designated as safety issue: No ]
  • Overall survival for the study for patients receiving at least one dose of pazopanib followed by everolimus [ Time Frame: Initiation of pazopanib until death for patients receiving at least one dose of pazopanib followed by everolimus, assessed up to 30 months after the last patient has been enrolled ] [ Designated as safety issue: No ]
  • Median progression free survival of patients treated with pazopanib [ Time Frame: Initiation of pazopanib until progression or death whichever comes first, provided this occurs prior to the commencement of everolimus and within 6 months of last dose of pazopanib, assessed up to 30 months after the last patient has been enrolled ] [ Designated as safety issue: No ]
  • Number of grade 3 or 4 adverse events attributable to everolimus [ Time Frame: Time of first dose of everolimus to approximately one month after discontinuation of everolimus ] [ Designated as safety issue: Yes ]
  • All grade 3 or 4 adverse events attributable to pazopanib and everolimus treatments [ Time Frame: Time of first dose of pazopanib to approximately one month after discontinuation of everolimus ] [ Designated as safety issue: Yes ]
  • Progression free survival proportion at three and six months after first everolimus dose [ Time Frame: Initiation of everolimus treatment until earliest date of disease progression or death, assessed at three and six months after first everolimus dose ] [ Designated as safety issue: No ]
  • Objective Response Rate to everolimus therapy [ Time Frame: Initiation of everolimus treatment until time of confirmed best response, assessed up to 30 months ] [ Designated as safety issue: No ]
  • Objective response rate to pazopanib therapy [ Time Frame: Initiation of pazopanib treatment until time of confirmed best response, assessed up to 30 months ] [ Designated as safety issue: No ]
  • Overall survival of patients treated with second-line everolimus therapy [ Time Frame: Initiation of everolimus dose until death, assessed up to 30 months ] [ Designated as safety issue: No ]
  • Overall survival for the study [ Time Frame: Enrolment in study until death, assessed up to 30 months ] [ Designated as safety issue: No ]
  • Median progression free survival of patients treated with pazopanib [ Time Frame: Enrolment until progression or death whichever comes first, assessed up to 30 months ] [ Designated as safety issue: No ]
  • Number of grade 3 or 4 adverse events attributable to everolimus [ Time Frame: Time of first dose of everolimus to approximately one month after discontinuation of everolimus ] [ Designated as safety issue: Yes ]
  • All grade 3 or 4 adverse events attributable to pazopanib and everolimus treatments [ Time Frame: Time of first dose of pazopanib to approximately one month after discontinuation of everolimus ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Everolimus Post Pazopanib Treatment in Metastatic or Advanced Renal Cell Carcinoma
Continuous Access to Advanced and Metastatic Renal Cell Carcinoma Therapy With Everolimus Post Pazopanib Treatment

Study to determine the efficacy, safety and tolerability of first-line pazopanib followed by second-line everolimus in metastatic and advanced renal cell carcinoma

A non-randomised, open label, single-arm phase II study to evaluate the efficacy and safety of 1st-line pazopanib followed by 2nd-line everolimus in patients with previously untreated advanced or metastatic renal cell carcinoma. Subjects will receive initial therapy with pazopanib, followed, on progression, by 2nd-line therapy with everolimus. Study treatment, sequential treatment with pazopanib followed by everolimus, will continue until disease progression, unacceptable toxicity, withdrawal of consent or death.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Carcinoma, Renal Cell
Drug: Pazopanib followed by everolimus
all patients will receive Pazopanib (800 mg once daily orally continuous dosing) until disease progression then second line everolimus (10 mg once daily orally continuous dosing)
Other Name: Pazopanib 1st line followed by Everolimus 2nd Line
Experimental: Pazopanib followed by everolimus
First line pazopanib, followed by second line everolimus
Intervention: Drug: Pazopanib followed by everolimus
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
74
September 2015
September 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Written informed consent
  2. Diagnosis of renal cell carcinoma with clear-cell component histology.
  3. Locally advanced/metastatic renal cell carcinoma
  4. Measurable lesion (RECIST 1.1) on physical exam or as CT/MRI
  5. No prior systemic therapy for advanced/metastatic RCC
  6. Karnofsky performance scale >=70
  7. Age >=18 years
  8. A female is eligible to enter and participate in this study if she is of: non-childbearing/agrees to use adequate contraception
  9. A male with female partner of childbearing potential must have vasectomy/agree to use effective contraception from two weeks prior to administration of the 1st dose of study treatment for a period of time after the last dose of study treatment
  10. Adequate organ function
  11. Able to swallow and retain orally administered medication and must not have clinically significant GIT abnormalities that may alter absorption

    Additional criterion for inclusion in the everolimus treatment:

  12. The date of disease progression must be within six months of stopping pazopanib or during treatment with pazopanib
  13. Measurable lesion at Everolimus C1D1 Scan (everolimus baseline) as per the RECIST 1.1 criteria
  14. Patients with radiotherapy prior to Everolimus treatment period will be eligible only if all below requirements are fulfilled:

    • The last radiotherapy fraction is delivered > 4 weeks prior to first dose of everolimus
    • The radiotherapy is not considered to be a second line treatment
    • The previously irradiated lesion(s) are not considered as target lesion(s) for everolimus RECIST 1.1 assessment
    • The radiotherapy field is not sufficiently close to the target lesion(s) so as to interfere with everolimus RECIST 1.1 assessments
    • There is no ongoing toxicity that is > Grade 1 and/or that is progressing in severity

16.Patients with central nervous system (CNS) progression or metastases during Pazopanib treatment period, will be eligible only if all below requirements are fulfilled:

  • Are asymptomatic and neurologically stable shown by no requirement for steroids (to control CNS symptoms) or enzyme-inducing anticonvulsants within 4 weeks prior to start of everolimus
  • If the lesion was previously been treated locally (by surgery ± radiotherapy, radiosurgery, or gamma knife) the last local treatment should be at least > 4 weeks prior to start of everolimus
  • Lesions that have been previously irradiated or in an area subjected to other loco‐regional therapy are not considered as target lesion(s) for everolimus RECIST 1.1 assessment
  • Have no presence of any non-healing wound

Exclusion Criteria:

  1. Pregnant/lactating
  2. History of another malignancy (unless have been disease-free for 3 years)
  3. History or clinical evidence of Central nervous system metastases (unless have previously-treated CNS metastases and who meet both of the following criteria: a) are asymptomatic and b) have no requirement for steroids or enzyme-inducing anticonvulsants in prior 6 month time interval.
  4. Clinically significant gastrointestinal abnormalities including, but not limited to: malabsorption syndrome, major resection of the stomach or small bowel that could affect the absorption of study drug, active peptic ulcer disease, known intraluminal metastatic lesion/s with suspected bleeding, Inflammatory bowel disease, ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation, history of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess
  5. Moderate to severe hepatic impairment (Child-Pugh Class C)
  6. Any serious and/or unstable pre-existing medical, psychiatric, or other conditions that could interfere with patient's safety, obtaining informed consent or compliance to the study.
  7. Subjects receiving chronic treatment with corticosteroids/other immunosuppressive agents
  8. Subjects with a known history of HIV seropositivity
  9. Subjects with active bleeding, bleeding diathesis or on oral anti-vitamin K medication (except low dose coumadin)
  10. Presence of any severe or uncontrolled medical conditions/infection.
  11. Currently receiving chemotherapy, immunotherapy or radiotherapy
  12. Corrected QT interval (QTc) > 480 milliseconds
  13. History of any one or more of the following cardiovascular conditions within the past 12 months: cardiac angioplasty or stenting, myocardial infarction, unstable angina, coronary artery by-pass graft surgery, symptomatic peripheral vascular disease, Class III or IV congestive heart failure, as defined by the New York Heart Association
  14. Poorly controlled hypertension (defined as systolic blood pressure of >=140mmHg or diastolic blood pressure of >=90mmHg).
  15. History of cerebrovascular accident including transient ischemic attack, pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months (unless recent DVT have been treated with therapeutic anti-coagulating agents for at least 6 weeks)
  16. Major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer.
  17. Evidence of active bleeding or bleeding susceptibility.
  18. Known endobronchial lesion and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrage
  19. Recent haemoptysis in excess of 2.5ml within eight weeks of first dose of study drug.
  20. Use of an investigational agent, including an investigational anti-cancer agent, within 30 days or 5 half-lives, whichever is longer, prior to the first dose of study drug.
  21. Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is progressing in severity, except alopecia.
  22. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib or everolimus, to other rapamycin derivatives or to any other excipients.

    Additional criterion for exclusion in the everolimus treatment:

  23. The subject is felt by the investigator to be unsuitable (on the basis of health, compliance, or for any other reason) for inclusion in the study.
  24. Presence of any severe and/or uncontrolled medical conditions
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Australia,   Korea, Republic of
 
NCT01545817
114907
No
GlaxoSmithKline
GlaxoSmithKline
Not Provided
Study Director: GSK Clinical Trials GlaxoSmithKline
GlaxoSmithKline
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP