Safety and Efficacy of Everolimus in Metastatic Renal Cell Carcinoma After Failure of First Line Therapy With Sunitinib or Pazopanib

An Open Label, Single Arm Trial to Evaluate Patients With Metastatic Renal Cell Carcinoma Treated With Everolimus After Failure of First Line Therapy With Sunitinib or Pazopanib

Patients with metastatic renal cell carcinoma (mRCC) who failed first-line therapy with sunitinib or pazopanib was treated with everolimus. Efficacy and safety of everolimus was evaluated in these patients.

Study Overview

• Status: Completed
• Conditions: Metastatic Renal Cell Carcinoma (mRCC)
• Intervention / Treatment: Drug: Everolimus (RAD001)

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Chemnitz, Germany, 09130
    • Novartis Investigative Site
  • Dresden, Germany, 01307
    • Novartis Investigative Site
  • Hannover, Germany, 30559
    • Novartis Investigative Site
  • Hof, Germany, 95028
    • Novartis Investigative Site
  • Kassel, Germany, 34125
    • Novartis Investigative Site
  • Langen, Germany, 63225
    • Novartis Investigative Site
  • Leipzig, Germany, 04357
    • Novartis Investigative Site
  • Magdeburg, Germany, 39120
    • Novartis Investigative Site
  • Muenster, Germany, 48149
    • Novartis Investigative Site
  • Ravensburg, Germany, 88214
    • Novartis Investigative Site
  • Velbert, Germany, 42551
    • Novartis Investigative Site
  • Wiesbaden, Germany, 65191
    • Novartis Investigative Site
  • Wolfsburg, Germany, 38440
    • 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:

• Patients with advanced renal cell carcinoma of a histological or cytological confirmation of clear cell renal carcinoma.
• Progression during or after a treatment with sunitinib or pazopanib given in a 1st line treatment situation for mRCC.
• Patients scheduled for treatment with everolimus.
• Patients with at least one measurable lesion at baseline as per RECIST v1.1.

Exclusion Criteria:

• Patients who have received >1 prior systemic treatment for their metastatic RCC. Prior systemic treatment in an adjuvant setting is allowed.
• Patients who have previously received systemic mTOR inhibitors (e.g. sirolimus, temsirolimus, everolimus).
• Patients who are using other investigational agents or who had received investigational drugs ≤ 2 weeks prior to study treatment start.
• Patients unwilling or unable to comply with the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Everolimus; Everolimus 10 mg orally once daily until disease progression, occurrence of intolerable toxicity, start of another anticancer treatment or withdrawn consent.	Drug: Everolimus (RAD001); Everolimus was used as commercially available formulated tablets of 10 mg strength; Other Names: RAD001

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Progression-free Patients by Month 6	Percentage of progression-free patients by month 6 after starting everolimus treatment. For the purpose of the binomial design of the study, a patient being 'progression-free' will be defined as a patient without disease progression by month 6 whereas a subject with progressive disease by month 6 will not be counted as 'progression-free'. The primary variable was derived from radiologic tumor assessments according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1.) Disease progression was either 1) a 20% increase in the sum of the longest diameter of all target lesions, taking as reference the smallest sum of the longest diameters of all target lesions recorded at or after baseline (minimum absolute increase 5 mm in sum) or 2) the appearance of a new lesion or 3) the unequivocal progression of non-target lesions overall.	Month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients With Overall Response Rate (ORR) Treated With Everolimus After Failure of First-line Sunitinib or Pazopanib Therapy at Month 6	Overall response rate (ORR) is the Percentage of patients with a best overall response of complete response (CR) or partial response (PR) by month 6. ORR was assessed according to RECIST 1.1 criteria. Partial response (PR) required at least a 30% decrease in the sum of the longest diameters of all target lesions, taking as reference the baseline sum of the longest diameters. Complete response (CR) required a disappearance of all target and non-target lesions.	Month 6
Progression-Free Survival (PFS) as the Time Interval Between First Intake of Everolimus and First Documented Disease Progression or Death Due to Any Cause at 24 Months	Progression-free survival (PFS) is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient did not have an event, progression-free survival was censored at the date of last adequate tumor assessment	24 months
Overall Survival (OS) of Patients Treated With Everolimus After Failure of First-line Sunitinib or Pazopanib Therapy up to 48 Months	Overall survival (OS) was defined as the time from date of start of treatment to date of death due to any cause. If a patient was not known to have died, survival will be censored at the date of last contact.	48 months
Duration of Response (DOR) in Patients Treated With Everolimus After Failure of First-line Sunitinib or Pazopanib Therapy up to 48 Months	The duration of overall response (DOR) was defined as the time from the first occurrence of a confirmed Complete Response (CR) or Partial Response (PR) (as per investigator assessment according to RECIST 1.1) until the date of the first documented disease progression or death due to underlying cancer. If a patient did not have an event or received any further anticancer therapy, duration of overall response was censored at the date of last adequate tumor assessment. Duration of response was displayed only for patients whose best overall response was CR or PR. As none of the patients showed any response (CR or PR), DOR could not be calculated	48 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): May 21, 2012
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: January 17, 2012
• First Submitted That Met QC Criteria: January 20, 2012
• First Posted (Estimate): January 23, 2012

Study Record Updates

• Last Update Posted (Actual): July 19, 2017
• Last Update Submitted That Met QC Criteria: July 17, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: sunitinib; Kidney cancer; everolimus; mRCC; pazopanib; metastic renal cell carcinoma
• 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: CRAD001LDE43; 2011-003416-23 (EudraCT Number)