Clinical trial NCT01545817: Everolimus Post Pazopanib Treatment in Metastatic or Advanced Renal Cell Carcinoma
Official title: Continuous Access to Advanced and Metastatic Renal Cell Carcinoma Therapy With Everolimus Post Pazopanib Treatment
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Carcinoma, Renal Cell
Keywords: Renal cell carcinoma (RCC), GW786034, Everolimus, Pazopanib, renal cancer, cancer, kidney cancer, hypernephroma, Grawitz tumor, renal adenocarcinoma.
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-03-07
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Progression Free Survival (PFS) for the Everolimus Treatment Period Using RECIST
timeFrame: Throughout the study period, up to 4 years
Secondary outcomes:
measure: Progression Free Survival (PFS) Rates
timeFrame: 3 months, 6 months
measure: Objective Response Rate (ORR) for the Everolimus Treatment Period Using RECIST
timeFrame: Throughout the study, up to 4 years
measure: Objective Response Rate (ORR) for the Pazopanib Treatment Period Using RECIST
timeFrame: Throughout the study period, up to 4 years
measure: Overall Survival of Everolimus (OSE)
timeFrame: Throughout the study period, up to 4 years
measure: Overall Survival From the Start (OSS) of Study Treatment
timeFrame: Throughout the study, up to 4 years
measure: PFS for the Pazopanib Treatment Period Using RECIST
timeFrame: Throughout the study period, up to 4 years
Other outcomes:
Locations:
city: Garran
country: Australia
facility: Novartis Investigative Site
state: Australian Capital Territory
city: Kogarah
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Auchenflower
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: Southport
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: Elizabeth Vale
country: Australia
facility: Novartis Investigative Site
state: South Australia
city: Kurralta Park
country: Australia
facility: Novartis Investigative Site
state: South Australia
city: Woodville
country: Australia
facility: Novartis Investigative Site
state: South Australia
city: Footscay
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Frankston
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Nedlands
country: Australia
facility: Novartis Investigative Site
state: Western Australia
city: Perth
country: Australia
facility: Novartis Investigative Site
state: Western Australia
city: Gyeonggi-do
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: