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)

Digestive System Diseases

Carcinoma, Hepatocellular

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Hematinics

Liver Extracts

Sorafenib

Cabozantinib (XL184) 60 mg tablet once daily

Oral cabozantinib-matched placebo tablet once daily

Placebo tablets

The purpose of this study is to evaluate the effect of Cabozantinib (XL184) compared with placebo on overall survival in subjects with advanced hepatocellular carcinoma who have received prior sorafenib.

Study of Cabozantinib (XL184) vs Placebo in Subjects With Hepatocellular Carcinoma Who Have Received Prior Sorafenib

A Phase 3, Randomized, Double-blind, Controlled Study of Cabozantinib (XL184) vs Placebo in Subjects With Hepatocellular Carcinoma Who Have Received Prior Sorafenib

The primary analysis of OS is defined as the time from randomization to death from any cause. The analysis was based on a second planned interim analysis prespecified to be performed at approximately the 75% information fraction (ie, at approximately 466 deaths). The data cutoff date for this event-driven analysis in the Intent to Treat (ITT) population was 01 June 2017. Median OS was calculated using the Kaplan-Meier estimates.

Duration of PFS is defined as the time of randomization to the earlier of the following events, progressive disease as determined by Investigator (per RECIST 1.0, which is defined by a ≥ 20% increase in the sum of the longest diameter of target lesions from baseline) or death due to any cause. A Kaplan- Meier analysis was performed to estimate the median duration.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

The safety data includes subjects who were randomized and treated. Of 707 patients, 470 were randomized to received cabozantinib and 237 to placebo. Three subjects in the cabozantinib arm were randomized but did not receive study drug. Thus, a total of 704 subjects received study treatment in the Safety Population (467 cabozantinib, 237 placebo).

Cabozantinib (XL184) 60 mg tablet once daily

Cabozantinib tablets

Oral cabozantinib-matched placebo tablet once daily

Placebo tablets

Placebo

Age, Continuous

Sex: Female, Male

Australia / New Zealand

Asia

North America (USA / Canada)

Interactive voice/web response system (IxRS)

Presence of extrahepatic spread of disease and/or macrovascular invasion (stratification per IxRS)

Etiology of disease (stratification factor per IxRS),

Geographic region (stratification factor per IxRS)

The ECOG performance scale is:

0 = Normal activity. Fully active, able to carry on all predisease performance without restriction, 1 = Symptoms, but ambulatory. Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature (eg, light housework, office work), 2 = In bed \< 50% of the time. Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours.

Eastern Cooperative Oncology Group Performance Status (ECOG PS)

Smoking history

Alcohol use

Weight

Body Mass Index (BMI)

The ITT population was used and included 707 randomized subjects (470 cabozantinib, 237 placebo) in the second interim analysis with a cutoff date of 01 June 2017.

The prespecified primary analysis of PFS was based on the first 707 randomized subjects (470 cabozantinib, 237 placebo).

Progression-Free Survival (PFS)

The analysis of ORR was performed in the ITT population (all randomized: 470 cabozantinib, 237 placebo) based upon response determined by Investigator per RECIST 1.1

Overall Study

Subjects will be enrolled in cohorts at different dose levels in order to determine the maximum tolerated dose of cabozantinib. Initially, subjects enrolled will receive the capsule formulation; other subjects will receive the tablet formulation.

cabozantinib capsules administered as 25-mg and 100-mg strengths once-daily until disease progression

cabozantinib capsules

cabozantinib tablets administered as 20-mg and 60-mg strengths once-daily until disease progression

cabozantinib tablets

The purpose of this study is to evaluate the safety profile, tolerability, pharmacokinetics (PK), pharmacodynamics, pharmacogenomic (PGX) and preliminary efficacy following daily oral doses of cabozantinib (XL184) in Japanese patients with advanced or metastatic solid tumors. Also, the effect of XL184 in the treatment of non-small cell lung cancer (NSCLC) patients with various activating mutations will be evaluated at the recommended Phase 2 dose.

Dose-Finding Study of Cabozantinib (XL184) in Japanese Subjects With Advanced Cancer

Phase 1 Multiple Ascending Dose Study of XL184 Monotherapy in Japanese Subjects With Advanced or Metastatic Solid Tumors

To establish the MTD and recommended Phase 2 dose (or dose range as appropriate) of XL184 when administered orally on a once daily schedule in subjects with advanced or metastatic solid tumors.

Safety and tolerability of multiple doses of XL184 administered orally on a daily basis. Assessed from informed consent until at least 30 days after discontinuation.

Assess plasma pharmacokinetics of daily oral administration of XL184 from Treatment Day 1 to Day 29.

Assess tumor response after repeated administration of XL184 from screening until discontinuation. Assessed as best overall response by cohort by radiological response defined by RECIST criteria.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Cabozantinib (XL184) vs Everolimus in Subjects With Metastatic Renal Cell Carcinoma	NCT01865747	Renal Cell Carc...	Cabozantinib ta... Everolimus (Afi...	18 Years -	Exelixis
Study of Cabozantinib (XL184) vs Placebo in Subjects With Hepatocellular Carcinoma Who Have Received Prior Sorafenib	NCT01908426	Hepatocellular ...	Cabozantinib ta... Placebo tablets	18 Years -	Exelixis
Dose-Finding Study of Cabozantinib (XL184) in Japanese Subjects With Advanced Cancer	NCT01553656	Solid Tumors Cancer NSCLC	cabozantinib ca... cabozantinib ta...	20 Years -	Exelixis

Spots Global Cancer Trial Database for cabozantinib tablets