Everolimus Post Pazopanib Treatment in Metastatic or Advanced Renal Cell Carcinoma

NCT01545817 | Terminated Phase 2 Results

• 1 other identifier: 114907
• Study Type: interventional
• Target: 74
• Locations: 2 countries
• Sites: 15

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.

Conditions

Carcinoma, Renal Cell

Keywords

Renal cell carcinoma (RCC), GW786034, Everolimus, Pazopanib, renal cancer, cancer, kidney cancer, hypernephroma, Grawitz tumor, renal adenocarcinoma.

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Progression Free Survival (PFS) Rates

  3 months, 6 months

• Objective Response Rate (ORR) for the Everolimus Treatment Period Using RECIST

  Throughout the study, up to 4 years

• Objective Response Rate (ORR) for the Pazopanib Treatment Period Using RECIST

  Throughout the study period, up to 4 years

• Overall Survival of Everolimus (OSE)

  Throughout the study period, up to 4 years

• Overall Survival From the Start (OSS) of Study Treatment

  Throughout the study, up to 4 years

Study Arms (1)

Pazopanib followed by everolimus

EXPERIMENTAL

First line pazopanib, followed by second line everolimus

Drug: Pazopanib followed by everolimus

Interventions

Pazopanib followed by everolimus DRUG

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)

Also known as: Pazopanib 1st line followed by everolimus 2nd line

Pazopanib followed by everolimus

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (15)

Novartis Investigative Site

Garran, Australian Capital Territory, 2606, Australia

Location

Novartis Investigative Site

Kogarah, New South Wales, 2217, Australia

Location

Novartis Investigative Site

Auchenflower, Queensland, 4066, Australia

Location

Novartis Investigative Site

Southport, Queensland, 4215, Australia

Location

Novartis Investigative Site

Elizabeth Vale, South Australia, 5112, Australia

Location

Novartis Investigative Site

Kurralta Park, South Australia, 5037, Australia

Location

Novartis Investigative Site

Woodville, South Australia, 5011, Australia

Location

Novartis Investigative Site

Footscay, Victoria, 3011, Australia

Location

Novartis Investigative Site

Frankston, Victoria, 3199, Australia

Location

Novartis Investigative Site

Nedlands, Western Australia, 6009, Australia

Location

Novartis Investigative Site

Perth, Western Australia, 6001, Australia

Location

Novartis Investigative Site

Gyeonggi-do, 10408, South Korea

Location

Novartis Investigative Site

Seoul, 03080, South Korea

Location

Novartis Investigative Site

Seoul, 135-710, South Korea

Location

Novartis Investigative Site

Seoul, 138-736, South Korea

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell; Kidney Neoplasms; Neoplasms

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Limitations and Caveats

the trial terminated early because the information gained from this study was sufficient to meet the objectives for which the study had been set up and would be no longer clinically relevant for the second-line management of RCC patients.

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2011
• First Posted: March 7, 2012
• Study Start: April 19, 2012
• Primary Completion: November 18, 2016
• Study Completion: November 18, 2016
• Last Updated: October 9, 2019
• Results First Posted: October 9, 2019

Record last verified: 2019-09

Locations

AU (11); KR (4)