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

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
• Conditions: Carcinoma, Renal Cell
• Intervention / Treatment: Drug: Pazopanib followed by everolimus

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

Study Locations

• Australia
  • 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
• Korea, Republic of
  • 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

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

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pazopanib followed by everolimus; First line pazopanib, followed by second line everolimus	Drug: Pazopanib followed by 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 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	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	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	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 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 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 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

• Sponsor: Novartis Pharmaceuticals

Study record dates

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

• Keywords: Renal cell carcinoma (RCC), GW786034, Everolimus, Pazopanib, renal cancer, cancer, kidney cancer, hypernephroma, Grawitz tumor, renal adenocarcinoma.
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma; Physiological Effects of Drugs; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Everolimus
• Other Study ID Numbers: 114907

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