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

September 20, 2019 updated by: Novartis Pharmaceuticals

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.

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.

Study Overview

Status

Terminated

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.

Study Type

Interventional

Enrollment (Actual)

74

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Australian Capital Territory
      • Garran, Australian Capital Territory, Australia, 2606
        • Novartis Investigative Site
    • New South Wales
      • Kogarah, New South Wales, Australia, 2217
        • Novartis Investigative Site
    • Queensland
      • Auchenflower, Queensland, Australia, 4066
        • Novartis Investigative Site
      • Southport, Queensland, Australia, 4215
        • Novartis Investigative Site
    • South Australia
      • Elizabeth Vale, South Australia, Australia, 5112
        • Novartis Investigative Site
      • Kurralta Park, South Australia, Australia, 5037
        • Novartis Investigative Site
      • Woodville, South Australia, Australia, 5011
        • Novartis Investigative Site
    • Victoria
      • Footscay, Victoria, Australia, 3011
        • Novartis Investigative Site
      • Frankston, Victoria, Australia, 3199
        • Novartis Investigative Site
    • Western Australia
      • Nedlands, Western Australia, Australia, 6009
        • Novartis Investigative Site
      • Perth, Western Australia, Australia, 6001
        • Novartis Investigative Site
      • Gyeonggi-do, Korea, Republic of, 10408
        • Novartis Investigative Site
      • Seoul, Korea, Republic of, 03080
        • Novartis Investigative Site
      • Seoul, Korea, Republic of, 138-736
        • Novartis Investigative Site
      • Seoul, Korea, Republic of, 135-710
        • Novartis Investigative Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pazopanib followed by everolimus
First line pazopanib, followed by second line everolimus
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)
Other Names:
  • Pazopanib 1st line followed by everolimus 2nd line

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS) for the Everolimus Treatment Period Using RECIST
Time Frame: Throughout the study period, up to 4 years

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).

Throughout the study period, up to 4 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS) Rates
Time Frame: 3 months, 6 months
PFS rates 3 and 6 months after date of first dose of second-line everolimus treatment.
3 months, 6 months
Objective Response Rate (ORR) for the Everolimus Treatment Period Using RECIST
Time Frame: Throughout the study, up to 4 years

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.

Throughout the study, up to 4 years
Objective Response Rate (ORR) for the Pazopanib Treatment Period Using RECIST
Time Frame: Throughout the study period, up to 4 years

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.

Throughout the study period, up to 4 years
Overall Survival of Everolimus (OSE)
Time Frame: Throughout the study period, up to 4 years
Time from first everolimus dose until death due to any cause
Throughout the study period, up to 4 years
Overall Survival From the Start (OSS) of Study Treatment
Time Frame: Throughout the study, up to 4 years
Time from first pazopanib dose until death due to any cause in patients who received at least one dose of pazopanib followed by everolimus
Throughout the study, up to 4 years
PFS for the Pazopanib Treatment Period Using RECIST
Time Frame: Throughout the study period, up to 4 years
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
Throughout the study period, up to 4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 19, 2012

Primary Completion (Actual)

November 18, 2016

Study Completion (Actual)

November 18, 2016

Study Registration Dates

First Submitted

November 17, 2011

First Submitted That Met QC Criteria

March 1, 2012

First Posted (Estimate)

March 7, 2012

Study Record Updates

Last Update Posted (Actual)

October 9, 2019

Last Update Submitted That Met QC Criteria

September 20, 2019

Last Verified

September 1, 2019

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

IPD 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

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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