Everolimus Post Pazopanib Treatment in Metastatic or Advanced Renal Cell Carcinoma

Phase 2

Terminated

Conditions: Carcinoma, Renal Cell

Interventions: Drug: Pazopanib followed by everolimus

Registration Number: NCT01545817

Lead Sponsor: Novartis Pharmaceuticals

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 74

Inclusion Criteria

Not provided

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 & Design

Study Type: INTERVENTIONAL

Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Pazopanib followed by everolimus	Pazopanib followed by everolimus	First line pazopanib, followed by second line everolimus

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS) for the Everolimus Treatment Period Using RECIST	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).

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) for the Everolimus Treatment Period Using RECIST	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.
PFS for the Pazopanib Treatment Period Using RECIST	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
Overall Survival of Everolimus (OSE)	Throughout the study period, up to 4 years	Time from first everolimus dose until death due to any cause
Progression Free Survival (PFS) Rates	3 months, 6 months	PFS rates 3 and 6 months after date of first dose of second-line everolimus treatment.
Overall Survival From the Start (OSS) of Study Treatment	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
Objective Response Rate (ORR) for the Pazopanib Treatment Period Using RECIST	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.