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
  Purpose

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


Condition Intervention Phase
Carcinoma, Renal Cell
Drug: Pazopanib followed by everolimus
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Continuous Access to Advanced and Metastatic Renal Cell Carcinoma Therapy With Everolimus Post Pazopanib Treatment

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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 ]

Enrollment: 74
Study Start Date: April 2012
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pazopanib followed by everolimus
First line pazopanib, followed by second line everolimus
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01545817

Locations
Australia, Australian Capital Territory
GSK Investigational Site
Garran, Australian Capital Territory, Australia, 2606
Australia, New South Wales
GSK Investigational Site
Kogarah, New South Wales, Australia, 2217
Australia, Queensland
GSK Investigational Site
Auchenflower, Queensland, Australia, 4066
GSK Investigational Site
Southport, Queensland, Australia, 4215
Australia, South Australia
GSK Investigational Site
Elizabeth Vale, South Australia, Australia, 5112
GSK Investigational Site
Kurralta Park, South Australia, Australia, 5037
GSK Investigational Site
Woodville, South Australia, Australia, 5011
Australia, Victoria
GSK Investigational Site
Footscay, Victoria, Australia, 3011
GSK Investigational Site
Frankston, Victoria, Australia, 3199
Australia, Western Australia
GSK Investigational Site
Nedlands, Western Australia, Australia, 6009
GSK Investigational Site
Perth, Western Australia, Australia, 6001
Korea, Republic of
GSK Investigational Site
Gyeonggi-do, Korea, Republic of, 410-769
GSK Investigational Site
Seoul, Korea, Republic of, 110-744
GSK Investigational Site
Seoul, Korea, Republic of, 138-736
GSK Investigational Site
Seoul, Korea, Republic of, 135-710
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01545817     History of Changes
Other Study ID Numbers: 114907
Study First Received: November 17, 2011
Last Updated: January 23, 2014
Health Authority: Australia: Human Research Ethics Committee

Keywords provided by GlaxoSmithKline:
Renal cell carcinoma
GW786034
Everolimus
Pazopanib

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Everolimus
Sirolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents

ClinicalTrials.gov processed this record on July 31, 2014