Everolimus Post Pazopanib Treatment in Metastatic or Advanced Renal Cell Carcinoma (CATChEz)
Primary Purpose
Carcinoma, Renal Cell
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Pazopanib followed by everolimus
Sponsored by
About this trial
This is an interventional treatment trial for Carcinoma, Renal Cell focused on measuring Renal cell carcinoma (RCC), GW786034, Everolimus, Pazopanib, renal cancer, cancer, kidney cancer, hypernephroma, Grawitz tumor, renal adenocarcinoma.
Eligibility Criteria
Inclusion criteria:
- Age >=18 years
- Histologically confirmed RCC with a clear-cell component
- Locally advanced or metastatic RCC
- At least one measurable lesion per RECIST 1.1 criteria, as determined by Computer Tomography (CT) Scan or Magnetic Resonance Imaging (MRI)
- No systemic therapy for advanced or metastatic RCC prior to enrollment
- Karnofsky Performance Status (KPS) ≥70
- Adequate baseline organ function
- A female was eligible to enter and participate in this study if she was of: non-childbearing potential, or negative serum pregnancy test with agreement to use adequate contraception during the study
- A male with female partner of childbearing potential must have vasectomy/agree to use effective contraception from 2 weeks prior to administration of the 1st dose of study treatment for a period of time after the last dose of study treatment
- Able to swallow and retain orally administered medication and must not have clinically significant GI abnormalities that may alter absorption
Additional inclusion criteria for starting everolimus:
- Disease progression must be within 6 months after stopping pazopanib
- At least one measurable lesion at the start of everolimus pe r RECIST 1.1 criteria, as determined by CT or MRI
- In case of central nervous system (CNS) progression or metastasis during pazopanib treatment: asymptomatic or neurologically stable, no requirement of steroids to control CNS symptoms, and no requirement of enzyme-inducing anticonvulsants within 4 weeks prior to the start of everolimus
Exclusion Criteria:
- Lactating female
- History of another malignancy (exception: patients disease-free for ≥3 years and patients with completely resected non-melanoma skin cancer or successfully treated in situ carcinoma)
- Symptomatic CNS metastases at baseline
- Clinically significant gastrointestinal abnormalities
- Moderate to severe hepatic impairment (Child Pugh Class C)
- Receiving chronic treatment with corticosteroids/other immunosuppressive agents
- Active bleeding, bleeding diathesis or on oral anti-vitamin K medication (except low dose coumadin)
- Corrected QT interval (QTc) >480 msec using Bazett's formula
- Presence of any severe or uncontrolled medical conditions/infection
- Poorly controlled hypertension (defined as systolic blood pressure of >=140mmHg or diastolic blood pressure of >=90mmHg)
- History of cardiovascular disorders within the last 12 months (e.g. myocardial infraction or unstable angina), history of cerebrovascular events or pulmonary embolism within the last 6 months
- Active bleeding or bleeding susceptibility
- Known endobronchial lesion and/or lesions infiltrating major pulmonary vessels that increased the risk of pulmonary hemorrhage
Additional criteria for exclusion from the second-line everolimus treatment period:
- The subject felt by the investigator to be unsuitable (on the basis of health, compliance, or for any other reason) for inclusion in the study.
Sites / Locations
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Pazopanib followed by everolimus
Arm Description
First line pazopanib, followed by second line everolimus
Outcomes
Primary Outcome Measures
Progression Free Survival (PFS) for the Everolimus Treatment Period Using RECIST
Time between the date of first everolimus dose and date of disease progression or death (whichever comes first) in patients treated initially with pazopanib.
Disease progression is measured by RECIST (Response Evaluation Criteria in Solid Tumors), which is at least a 20% increase in the sum of the target lesion longest diameters (LDs).
Secondary Outcome Measures
Progression Free Survival (PFS) Rates
PFS rates 3 and 6 months after date of first dose of second-line everolimus treatment.
Objective Response Rate (ORR) for the Everolimus Treatment Period Using RECIST
Percentage of patients with Complete or Partial Response at any time following the start of second-line everolimus treatment as per RECIST.
RECIST Complete Response is defined to be a disappearance of all target lesion(s). RECIST Partial Response is defined to be at least a 30% decrease in the sum of the target lesion LDs.
Objective Response Rate (ORR) for the Pazopanib Treatment Period Using RECIST
Percentage of patients with Complete or Partial Response at any time following the start of first-line pazopanib treatment.
RECIST Complete Response is defined to be a disappearance of all target lesion(s). RECIST Partial Response is defined to be at least a 30% decrease in the sum of the target lesion LDs.
Overall Survival of Everolimus (OSE)
Time from first everolimus dose until death due to any cause
Overall Survival From the Start (OSS) of Study Treatment
Time from first pazopanib dose until death due to any cause in patients who received at least one dose of pazopanib followed by everolimus
PFS for the Pazopanib Treatment Period Using RECIST
Time from first pazopanib dose until disease progression or death from any cause (whichever occurred earlier), provided this occurred prior to the start of everolimus and within 6 months of last dose of pazopanib
Full Information
NCT ID
NCT01545817
First Posted
November 17, 2011
Last Updated
September 20, 2019
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT01545817
Brief Title
Everolimus Post Pazopanib Treatment in Metastatic or Advanced Renal Cell Carcinoma
Acronym
CATChEz
Official Title
Continuous Access to Advanced and Metastatic Renal Cell Carcinoma Therapy With Everolimus Post Pazopanib Treatment
Study Type
Interventional
2. Study Status
Record Verification Date
September 2019
Overall Recruitment Status
Terminated
Why Stopped
As the therapeutic landscape in renal cell carcinoma is changing, it has become apparent that information gained so far by CATChEz study is sufficient.
Study Start Date
April 19, 2012 (Actual)
Primary Completion Date
November 18, 2016 (Actual)
Study Completion Date
November 18, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Study to determine the efficacy, safety and tolerability of first-line pazopanib followed by second-line everolimus in metastatic and advanced renal cell carcinoma.
Due to changes in the RCC treatment landscape, info gained is no longer clinically relevant to patients. Data collected is deemed sufficient to meet objective.
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 received initial therapy with pazopanib followed, on progression, by 2nd-line therapy with everolimus. Study treatment - sequential treatment with pazopanib followed by everolimus - to continue until disease progression, unacceptable toxicity, withdrawal of consent, or death.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Renal Cell
Keywords
Renal cell carcinoma (RCC), GW786034, Everolimus, Pazopanib, renal cancer, cancer, kidney cancer, hypernephroma, Grawitz tumor, renal adenocarcinoma.
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Masking
None (Open Label)
Enrollment
74 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pazopanib followed by everolimus
Arm Type
Experimental
Arm Description
First line pazopanib, followed by second line everolimus
Intervention Type
Drug
Intervention Name(s)
Pazopanib followed by everolimus
Other Intervention Name(s)
Pazopanib 1st line followed by everolimus 2nd line
Intervention Description
All patients received Pazopanib (800 mg once daily orally continuous dosing) until disease progression then second line everolimus (10 mg once daily orally continuous dosing)
Primary Outcome Measure Information:
Title
Progression Free Survival (PFS) for the Everolimus Treatment Period Using RECIST
Description
Time between the date of first everolimus dose and date of disease progression or death (whichever comes first) in patients treated initially with pazopanib.
Disease progression is measured by RECIST (Response Evaluation Criteria in Solid Tumors), which is at least a 20% increase in the sum of the target lesion longest diameters (LDs).
Time Frame
Throughout the study period, up to 4 years
Secondary Outcome Measure Information:
Title
Progression Free Survival (PFS) Rates
Description
PFS rates 3 and 6 months after date of first dose of second-line everolimus treatment.
Time Frame
3 months, 6 months
Title
Objective Response Rate (ORR) for the Everolimus Treatment Period Using RECIST
Description
Percentage of patients with Complete or Partial Response at any time following the start of second-line everolimus treatment as per RECIST.
RECIST Complete Response is defined to be a disappearance of all target lesion(s). RECIST Partial Response is defined to be at least a 30% decrease in the sum of the target lesion LDs.
Time Frame
Throughout the study, up to 4 years
Title
Objective Response Rate (ORR) for the Pazopanib Treatment Period Using RECIST
Description
Percentage of patients with Complete or Partial Response at any time following the start of first-line pazopanib treatment.
RECIST Complete Response is defined to be a disappearance of all target lesion(s). RECIST Partial Response is defined to be at least a 30% decrease in the sum of the target lesion LDs.
Time Frame
Throughout the study period, up to 4 years
Title
Overall Survival of Everolimus (OSE)
Description
Time from first everolimus dose until death due to any cause
Time Frame
Throughout the study period, up to 4 years
Title
Overall Survival From the Start (OSS) of Study Treatment
Description
Time from first pazopanib dose until death due to any cause in patients who received at least one dose of pazopanib followed by everolimus
Time Frame
Throughout the study, up to 4 years
Title
PFS for the Pazopanib Treatment Period Using RECIST
Description
Time from first pazopanib dose until disease progression or death from any cause (whichever occurred earlier), provided this occurred prior to the start of everolimus and within 6 months of last dose of pazopanib
Time Frame
Throughout the study period, up to 4 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria:
Age >=18 years
Histologically confirmed RCC with a clear-cell component
Locally advanced or metastatic RCC
At least one measurable lesion per RECIST 1.1 criteria, as determined by Computer Tomography (CT) Scan or Magnetic Resonance Imaging (MRI)
No systemic therapy for advanced or metastatic RCC prior to enrollment
Karnofsky Performance Status (KPS) ≥70
Adequate baseline organ function
A female was eligible to enter and participate in this study if she was of: non-childbearing potential, or negative serum pregnancy test with agreement to use adequate contraception during the study
A male with female partner of childbearing potential must have vasectomy/agree to use effective contraception from 2 weeks prior to administration of the 1st dose of study treatment for a period of time after the last dose of study treatment
Able to swallow and retain orally administered medication and must not have clinically significant GI abnormalities that may alter absorption
Additional inclusion criteria for starting everolimus:
Disease progression must be within 6 months after stopping pazopanib
At least one measurable lesion at the start of everolimus pe r RECIST 1.1 criteria, as determined by CT or MRI
In case of central nervous system (CNS) progression or metastasis during pazopanib treatment: asymptomatic or neurologically stable, no requirement of steroids to control CNS symptoms, and no requirement of enzyme-inducing anticonvulsants within 4 weeks prior to the start of everolimus
Exclusion Criteria:
Lactating female
History of another malignancy (exception: patients disease-free for ≥3 years and patients with completely resected non-melanoma skin cancer or successfully treated in situ carcinoma)
Symptomatic CNS metastases at baseline
Clinically significant gastrointestinal abnormalities
Moderate to severe hepatic impairment (Child Pugh Class C)
Receiving chronic treatment with corticosteroids/other immunosuppressive agents
Active bleeding, bleeding diathesis or on oral anti-vitamin K medication (except low dose coumadin)
Corrected QT interval (QTc) >480 msec using Bazett's formula
Presence of any severe or uncontrolled medical conditions/infection
Poorly controlled hypertension (defined as systolic blood pressure of >=140mmHg or diastolic blood pressure of >=90mmHg)
History of cardiovascular disorders within the last 12 months (e.g. myocardial infraction or unstable angina), history of cerebrovascular events or pulmonary embolism within the last 6 months
Active bleeding or bleeding susceptibility
Known endobronchial lesion and/or lesions infiltrating major pulmonary vessels that increased the risk of pulmonary hemorrhage
Additional criteria for exclusion from the second-line everolimus treatment period:
- The subject felt by the investigator to be unsuitable (on the basis of health, compliance, or for any other reason) for inclusion in the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Garran
State/Province
Australian Capital Territory
ZIP/Postal Code
2606
Country
Australia
Facility Name
Novartis Investigative Site
City
Kogarah
State/Province
New South Wales
ZIP/Postal Code
2217
Country
Australia
Facility Name
Novartis Investigative Site
City
Auchenflower
State/Province
Queensland
ZIP/Postal Code
4066
Country
Australia
Facility Name
Novartis Investigative Site
City
Southport
State/Province
Queensland
ZIP/Postal Code
4215
Country
Australia
Facility Name
Novartis Investigative Site
City
Elizabeth Vale
State/Province
South Australia
ZIP/Postal Code
5112
Country
Australia
Facility Name
Novartis Investigative Site
City
Kurralta Park
State/Province
South Australia
ZIP/Postal Code
5037
Country
Australia
Facility Name
Novartis Investigative Site
City
Woodville
State/Province
South Australia
ZIP/Postal Code
5011
Country
Australia
Facility Name
Novartis Investigative Site
City
Footscay
State/Province
Victoria
ZIP/Postal Code
3011
Country
Australia
Facility Name
Novartis Investigative Site
City
Frankston
State/Province
Victoria
ZIP/Postal Code
3199
Country
Australia
Facility Name
Novartis Investigative Site
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Facility Name
Novartis Investigative Site
City
Perth
State/Province
Western Australia
ZIP/Postal Code
6001
Country
Australia
Facility Name
Novartis Investigative Site
City
Gyeonggi-do
ZIP/Postal Code
10408
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
135-710
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
138-736
Country
Korea, Republic of
12. IPD Sharing Statement
Plan to Share IPD
Undecided
IPD Sharing Plan Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Learn more about this trial
Everolimus Post Pazopanib Treatment in Metastatic or Advanced Renal Cell Carcinoma
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