Everolimus Post Pazopanib Treatment in Metastatic or Advanced Renal Cell Carcinoma

Carcinoma, Renal Cell Clinical Trial

— CATChEz  

Official title:

Continuous Access to Advanced and Metastatic Renal Cell Carcinoma Therapy With Everolimus Post Pazopanib Treatment

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01545817
• Other study ID #: 114907
• Status: Terminated
• Phase: Phase 2
• Start date: April 19, 2012
• Est. completion date: November 18, 2016

Study information

• Verified date: September 2019
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 74
• Est. completion date: November 18, 2016
• Est. primary completion date: November 18, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell

Intervention

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)

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Auchenflower	Queensland
Australia	Novartis Investigative Site	Elizabeth Vale	South Australia
Australia	Novartis Investigative Site	Footscay	Victoria
Australia	Novartis Investigative Site	Frankston	Victoria
Australia	Novartis Investigative Site	Garran	Australian Capital Territory
Australia	Novartis Investigative Site	Kogarah	New South Wales
Australia	Novartis Investigative Site	Kurralta Park	South Australia
Australia	Novartis Investigative Site	Nedlands	Western Australia
Australia	Novartis Investigative Site	Perth	Western Australia
Australia	Novartis Investigative Site	Southport	Queensland
Australia	Novartis Investigative Site	Woodville	South Australia
Korea, Republic of	Novartis Investigative Site	Gyeonggi-do
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Australia,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	Overall Survival of Everolimus (OSE)	Time from first everolimus dose until death due to any cause	Throughout the study period, up to 4 years
Secondary	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
Secondary	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