Safety And Effectiveness Of Daily Dosing With 37.5 mg Sunitinib Malate In Patients With Advanced Kidney Cancer

A Phase II Efficacy And Safety Study Of Sunitinib Malate (SU011248) Administered In A Continuous Daily Regimen In Patients With Advanced (First-Line) Renal Cell Cancer

A phase II study to allow patients with advanced kidney cancer access to sunitinib malate treatment and to find out the good and bad effects of taking 37.5 mg sunitinib malate in a continuous daily regimen (once per day) for one year.

Study Overview

• Status: Completed
• Conditions: Carcinoma, Renal Cell
• Intervention / Treatment: Drug: Sunitinib malate

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1431
    • Pfizer Investigational Site
  • Cordoba, Argentina, X5000AAI
    • Pfizer Investigational Site
  • Santa Fé
    • Rosario, Santa Fé, Argentina, (2000)
      • Pfizer Investigational Site
• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Pfizer Investigational Site
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Pfizer Investigational Site
    • East Bentleigh, Victoria, Australia, 3165
      • Pfizer Investigational Site
• Brazil
  • RS
    • Porto Alegre, RS, Brazil, 90610-000
      • Pfizer Investigational Site
  • SP
    • São Paulo, SP, Brazil, 01308-050
      • Pfizer Investigational Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 120-752
    • Pfizer Investigational Site
  • Seoul, Korea, Republic of, 110-744
    • Pfizer Investigational Site
• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44280
      • Pfizer Investigational Site
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64460
      • Pfizer Investigational Site
• Taiwan
  • Taichung, Taiwan, 407
    • Pfizer Investigational Site
  • Tainan, Taiwan, 710
    • Pfizer Investigational Site
  • Taipei, Taiwan, 112
    • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Advanced kidney cancer

Exclusion Criteria:

• Previous treatment for kidney cancer, except surgical removal of kidney tumor

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SUNITINIB MALATE.; Sunitinib malate starting dose 37.5 mg daily continuous daily schedule	Drug: Sunitinib malate; Sunitinib malate starting dose 37.5 mg daily continuous daily schedule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Overall Confirmed Objective Response (OR)	OR = subjects with confirmed complete response (CR) or partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) persisting > = 4 weeks after initial documentation of response. A CR was defined as the disappearance of all target lesions. A PR was defined as a ≥ 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.	From start of treatment through Day 1 of Weeks 5, 9, and every 8 weeks thereafter

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DR)	Time from start of the first documentation of objective tumor response (CR or PR) to the first documentation of objective tumor progression or to death due to to any cause, whichever occurred first. If tumor progression data included more than 1 date, the first date was used. DR was calculated as [the end date for DR minus first CR or PR that was subsequently confirmed +1]/7.	From start of treatment through Day 1 of Weeks 5, 9, and every 8 weeks thereafter or death due to any cause
Time to Tumor Progression (TTP)	Time from date of first dose of study medication to first documentation of objective tumor progression. The 50% quartile point estimate is provided. The criteria for tumor progression was according to RECIST.	From start of treatment through Day 1 of Weeks 5, 9, and every 8 weeks thereafter
Progression-Free Survival (PFS)	Time from start of study medication to first documentation of objective tumor progression or to death due to any cause, whichever occurred first. If tumor progression data included more than 1 date, the first date was used. PFS (in months) was calculated as (first event date minus first dose date +1)/7.	From start of treatment through Day 1 of Weeks 5, 9, and every 8 weeks thereafter or death
1-Year Survival	One year survival rate defined as the probability that a subject was alive 1 year after the date of first study treatment.	From start of treatment through Day 1 of Weeks 5, 9, and every 8 weeks thereafter up until 1 year
Trough Plasma Concentrations (Ctrough) of Sunitinib	Ctrough = the concentration prior to study drug administration.	Predose on Day 1 of Weeks 1, 3, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53
Ctrough Stratified by CR or PR Versus Progressive Disease (PD) for Sunitinib	Summary statistics of ctrough at each time point by group (CR or PR versus PD) are presented.	Predose on Day 1 of Weeks 1, 3, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53
Ctrough Stratified by Tumor Response (CR or PR or [Stable Disease (SD) > = 12 Weeks] Versus PD) for Sunitinib	Summary statistics of ctrough at each time point by group (CR or PR or SD versus PD) are presented.	Predose on Day 1 of Weeks 1, 3, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53
Ctrough of SU-012662 (Sunitinib's Metabolite)	Ctrough = the concentration prior to study drug administration.	Predose on Day 1 of Weeks 1, 3, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53
Ctrough Stratified by CR or PR Versus PD for SU-012662 (Sunitinib's Metabolite)	Summary statistics of ctrough at each time point by group (CR or PR versus PD) are presented.	Predose on Day 1 of Weeks 1, 3, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53
Ctrough Stratified by Tumor Response (CR or PR or [SD > = 12 Weeks] Versus PD) for SU-012662 (Sunitinib's Metabolite)	Summary statistics of ctrough at each time point by group (CR or PR or SD versus PD) are presented.	Predose on Day 1 of Weeks 1, 3, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53
Ctrough of Total Drug (Sunitinib + SU-012662)	Ctrough = the concentration prior to study drug administration.	Predose on Day 1 of Weeks 1, 3, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53
Ctrough Stratified by CR or PR Versus PD for Total Drug (Sunitinib + SU012662)	Summary statistics of ctrough at each time point by group (CR or PR versus PD) are presented.	Predose on Day 1 of Weeks 1, 3, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53
Ctrough Stratified by Tumor Response (CR or PR or [SD > = 12 Weeks] Versus PD) for Total Drug (Sunitinib + SU012662)	Summary statistics of ctrough at each time point by group (CR or PR or SD versus PD) are presented.	Predose on Day 1 of Weeks 1, 3, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53
Ctrough Correlated With Serious Adverse Events (SAEs)	Serious adverse event defined as any untoward medical occurrence at any dose that: Results in death; Is life-threatening (immediate risk of death); Requires inpatient hospitalization or prolongation of existing hospitalization; Results in persistent or significant disability/incapacity; Results in congenital anomaly/birth defect.	Predose on Day 1 of Weeks 1, 3, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53
Vascular Endothelial Growth Factor (VEGF) Concentration at Baseline		Baseline
VEGF at Baseline Stratified by Tumor Response (CR or PR Versus PD)	Summary statistics of VEGF at baseline by group (CR or PR versus PD) are presented.	Baseline (Cycle 1, Day 1)
VEGF at Baseline Stratified by Tumor Response (CR or PR or [SD > = 12 Weeks] Versus PD)	Summary statistics of VEGF at baseline by group (CR or PR or SD versus PD) are presented.	Baseline (Cycle 1, Day 1)
VEGF Ratio to Baseline at Each Time Point	VEGF concentration at each time point divided by VEGF concentration at baseline (ratio to baseline).	Baseline to Day 1 of Weeks 3 through 53
VEGF Ratio to Baseline Stratified by Tumor Response (CR or PR Versus PD)	Median VEGF concentration at each time point divided by VEGF concentration at baseline (ratio to baseline) for subjects with tumor response (CR or PR versus PD).	Baseline to Day 1 of Weeks 3 through 53
VEGF Ratio to Baseline Stratified by Tumor Response (CR or PR or [SD > = 12 Weeks] Versus PD)	Median VEGF concentration at each time point divided by VEGF concentration at baseline (ratio to baseline) for subjects with tumor response (CR or PR or [SD > = 12 weeks] versus PD).	Baseline to Day 1 of Weeks 3 through 53
Soluble VEGF Receptor 2 (sVEGFR2) Concentration at Baseline		Baseline
sVEGFR2 at Baseline Stratified by Tumor Response (CR or PR Versus PD)	Summary statistics of sVEGFR2 at baseline by group (CR or PR versus PD) are presented.	Baseline (Cycle 1, Day 1)
sVEGFR2 at Baseline Stratified by Tumor Response (CR or PR or [SD > = 12 Weeks] Versus PD)	Summary statistics of sVEGFR2 at baseline by group (CR or PR or SD versus PD) are presented.	Baseline (Cycle 1, Day 1)
sVEGFR2 Ratio to Baseline at Each Time Point	sVEGFR2 concentration at each time point divided by sVEGFR2 concentration at baseline (ratio to baseline).	Baseline to Day 1 of Weeks 3 through 53
sVEGFR2 Ratio to Baseline Stratified by Tumor Response (CR or PR Versus PD)	Median sVEGFR2 concentration at each time point divided by sVEGFR2 concentration at baseline (ratio to baseline) for subjects with tumor response (CR or PR versus PD).	Baseline to Day 1 of Weeks 3 through 53
sVEGFR2 Ratio to Baseline Stratified by Tumor Response (CR or PR or [SD > = 12 Weeks] Versus PD)	Median sVEGFR2 concentration at each time point divided by sVEGFR2 concentration at baseline (ratio to baseline) for subjects with tumor response (CR or PR or [SD > = 12 weeks] versus PD).	Baseline to Day 1 of Weeks 3 through 53
Patient-Assessed Fatigue	Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Scale: Overall score from 13-question questionnaire (measures fatigue/asthenia for patients with chronic, life-threatening illnesses). For each question, patient rates condition for the past week on a 5-point Likert scale ranging from 0 (not at all) to 4 (very much). Total FACIT-Fatigue score = sum score of the 13 question scores; total range: 0 - 52; higher total score represents less fatigue. End of treatment assessment was for subjects who completed the study only.	Baseline (Day 1, Week 1), Day 1 of Weeks 3, 5, 7, 9, 11, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, Week 53 (End of Treatment)
Cancer Related Symptoms, Well-Being, and Concerns	FACT-Advanced Kidney Cancer Symptom Index (FKSI) Questionnaire: subscale designed to be a stand-alone instrument to measure symptoms and quality of life in patients with advanced kidney cancer. Contains 15 questions. Each question was answered on a 5-point Likert-type scale ranging from 0 to 4 (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much). Total FKSI score = sum score of the 15 item scores; total range: 0 - 60; 0 (most severe symptoms and concerns) to 60 (no symptoms or concerns). End of treatment assessment was for subjects who completed the study only.	Baseline (Day 1, Week 1), Day 1 of Weeks 3, 5, 7, 9, 11, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, Week 53 (End of Treatment)

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• de Velasco G, McKay RR, Lin X, Moreira RB, Simantov R, Choueiri TK. Comprehensive Analysis of Survival Outcomes in Non-Clear Cell Renal Cell Carcinoma Patients Treated in Clinical Trials. Clin Genitourin Cancer. 2017 Dec;15(6):652-660.e1. doi: 10.1016/j.clgc.2017.03.004. Epub 2017 Mar 21.
• Grunwald V, Lin X, Kalanovic D, Simantov R. Early Tumour Shrinkage: A Tool for the Detection of Early Clinical Activity in Metastatic Renal Cell Carcinoma. Eur Urol. 2016 Dec;70(6):1006-1015. doi: 10.1016/j.eururo.2016.05.010. Epub 2016 May 26.
• Grunwald V, McKay RR, Krajewski KM, Kalanovic D, Lin X, Perkins JJ, Simantov R, Choueiri TK. Depth of remission is a prognostic factor for survival in patients with metastatic renal cell carcinoma. Eur Urol. 2015 May;67(5):952-8. doi: 10.1016/j.eururo.2014.12.036. Epub 2015 Jan 7.
• Barrios CH, Hernandez-Barajas D, Brown MP, Lee SH, Fein L, Liu JH, Hariharan S, Martell BA, Yuan J, Bello A, Wang Z, Mundayat R, Rha SY. Phase II trial of continuous once-daily dosing of sunitinib as first-line treatment in patients with metastatic renal cell carcinoma. Cancer. 2012 Mar 1;118(5):1252-9. doi: 10.1002/cncr.26440. Epub 2011 Sep 6.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: September 1, 2006
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: June 16, 2006
• First Submitted That Met QC Criteria: June 19, 2006
• First Posted (Estimate): June 20, 2006

Study Record Updates

• Last Update Posted (Estimate): August 31, 2012
• Last Update Submitted That Met QC Criteria: August 22, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Sunitinib
• Other Study ID Numbers: A6181110