Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Nervous System Diseases

Heart and Blood Diseases

Diseases and Abnormalities at or Before Birth

Rare Diseases

Carcinoma

Carcinoma, Renal Cell

Von Hippel-Lindau Disease

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Amino Acids

Everolimus

Endothelial Growth Factors

Mitogens

Tyrosine Kinase Inhibitors

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

Tyrosine

Cabozantinib (XL184) 60 mg tablet once daily.

Everolimus (Afinitor) 10 mg tablet once daily.

Cabozantinib tablets

Everolimus (Afinitor) tablets

The purpose of this study is to evaluate the effect of Cabozantinib (XL184) compared with Everolimus (Afinitor) on progression-free survival (PFS) and overall survival (OS) in subjects with advanced renal cell cancer that has progressed after prior VEGFR tyrosine kinase inhibitor therapy.

A Study of Cabozantinib (XL184) vs Everolimus in Subjects With Metastatic Renal Cell Carcinoma

A Phase 3, Randomized, Controlled Study of Cabozantinib (XL184) vs Everolimus in Subjects With Metastatic Renal Cell Carcinoma That Has Progressed After Prior VEGFR Tyrosine Kinase Inhibitor Therapy

The primary analysis of PFS is the time from randomization to date of first documented tumor progression as determined by investigator (per RECIST 1.1 criteria) or death due to any cause, whichever occurred first. A Kaplan-Meier analysis was performed to estimate the median duration.

Overall Survival (OS) is defined as the time from randomization to the date of death. Participants that had not died were censored at last known date alive. Median OS was calculated using Kaplan-Meier estimates. Interim analyses for OS occurred after 320 deaths (78% of the total OS events needed for final analysis).

Objective Response Rate (ORR) is the number of participants with a best response of complete response (CR) or partial response (PR) divided by number of randomized participants. ORR was assessed by the Independent Radiology Committee (IRC) per RECIST 1.1 which was confirmed by a subsequent visit \>= 28 days later, and was analyzed in the Intent to Treat (ITT) population at the time of the primary analysis of Progression Free Survival (PFS). The data cutoff date was 22 May 2015.

Exelixis

The safety data includes subjects who were randomized and treated. Of 658 patients, 330 were randomized to receive cabozantinib and 328 everolimus. Five subjects in the everolimus arm were randomized but not treated. One subject randomized to the everolimus arm received cabozantinib only as study treatment and was evaluated in the cabozantinib arm for the Safety population (331 cabozantinib, 322 everolimus).

Cabozantinib (XL184) 60 mg tablet once daily.

Cabozantinib tablets

Cabozantinib (XL184)

Everolimus (Afinitor) 10 mg tablet once daily.

Everolimus (Afinitor) tablets

Everolimus (Afinitor)

Total

65 to <75

75 to <85

=>85

Age, Customized

Male

Female

Missing

Sex/Gender, Customized

Ethnicity

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Europe

North America

Asia Pacific

Latin America

Geographic Region

Prior VEGFR-TKI = 1

Prior VEGFR-TKI ≥ 2

MSKCC risk factors = 0

MSKCC risk factors = 1

MSKCC risk factors = 2 or 3

Prior VEGFR-TKI = 1, MSKCC risk factors = 0

Prior VEGFR-TKI = 1, MSKCC risk factors = 1

Prior VEGFR-TKI = 1, MSKCC risk factors = 2 or 3

Prior VEGFR-TKI ≥ 2, MSKCC risk factors =0

Prior VEGFR-TKI ≥ 2, MSKCC risk factors = 1

Prior VEGFR-TKI ≥ 2, MSKCC risk factors = 2 or 3

Randomization Stratification Factors per CRF

100 (normal activity)

90 (normal activity, minor signs and symptoms)

80 (normal w/effort, minor signs/symptoms)

70 (unable to work, cares for self)

Karnofsky performance status (KPS)

0 adverse factors (favorable risk)

1-2 adverse factors (intermediate risk)

3-6 adverse factors (poor risk)

Heng Prognostic Criteria

Exelixis Medical Information

The pre-specified primary analysis of PFS was based on the first 375 randomized subjects (187 cabozantinib and 188 everolimus).

Progression-free Survival (PFS)

The Intent to Treat (ITT) population was used and included 658 randomized subjects (330 cabozantinib, 328 everolimus) in the second interim analysis with a cutoff date of 31 December 2015.

Overall Survival (OS)

The analysis of ORR was performed in the ITT population (all randomized: 330 cabozantinib, 328 everolimus) based upon response determined by Independent Radiology Committee (IRC) per RECIST 1.1.

Objective Response Rate (ORR)

Overall Study (ITT)

Primary Intent to Treat (PITT)

Spots Global Cancer Trial Database for everolimus (afinitor) tablets