Sunitinib Malate Schedule 4/2 vs. Sunitinib Malate Continuous Dosing As First-Line Therapy For Metastatic Renal Cell Cancer (RCC)

A Randomized Phase II Study Of The Efficacy And Safety Of Sunitinib Malate Schedule 4/2 vs. Sunitinib Malate Continuous Dosing As First-Line Therapy For Metastatic Renal Cell Cancer (Renal EFFECT Trial)

This trial has two parts. The purpose of the first part of the trial is to determine the doses of 2 drugs, sunitinib malate and interferon alfa-2b, that can be given safely in combination. This part is currently closed to enrollment.

The purpose of the second part of the trial is to see if sunitinib malate given on a 4/2 schedule (4 weeks on treatment, 2 weeks off treatment cycle) is any better at delaying progression of renal cell cancer than sunitinib malate given on a continuous dosing schedule. The trial will also determine the number of patients whose cancer responds to the treatments, whether life of patients can be extended, what the side effects are of the treatments, how bothersome disease or treatment-related symptoms are to patients, and whether tests can be found that will predict which patients may or may not respond to these treatments in the future.

Study Overview

• Status: Completed
• Conditions: Carcinoma, Renal Cell
• Intervention / Treatment: Drug: Sunitinib Malate Continuous Daily Dosing; Drug: Sunitinib Malate Schedule 4/2

• Study Type: Interventional
• Enrollment (Actual): 317
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • Pfizer Investigational Site
    • Little Rock, Arkansas, United States, 72205
      • Pfizer Investigational Site
  • California
    • Anaheim, California, United States, 92807
      • Pfizer Investigational Site
    • Baldwin Park, California, United States, 91706
      • Pfizer Investigational Site
    • Bellflower, California, United States, 90706
      • Pfizer Investigational Site
    • Duarte, California, United States, 91010
      • Pfizer Investigational Site
    • Fontana, California, United States, 92335
      • Pfizer Investigational Site
    • Irvine, California, United States, 92618
      • Pfizer Investigational Site
    • Los Angeles, California, United States, 90095
      • Pfizer Investigational Site
    • Los Angeles, California, United States, 90027
      • Pfizer Investigational Site
    • Los Angeles, California, United States, 90034
      • Pfizer Investigational Site
    • Panorama City, California, United States, 91402
      • Pfizer Investigational Site
    • Riverside, California, United States, 92505
      • Pfizer Investigational Site
    • San Diego, California, United States, 92108
      • Pfizer Investigational Site
    • San Diego, California, United States, 92120
      • Pfizer Investigational Site
    • Woodland Hills, California, United States, 91365
      • Pfizer Investigational Site
  • Colorado
    • Aurora, Colorado, United States, 80012
      • Pfizer Investigational Site
    • Boulder, Colorado, United States, 80304
      • Pfizer Investigational Site
    • Boulder, Colorado, United States, 80303
      • Pfizer Investigational Site
    • Colorado Springs, Colorado, United States, 80909
      • Pfizer Investigational Site
    • Denver, Colorado, United States, 80220
      • Pfizer Investigational Site
    • Denver, Colorado, United States, 80218
      • Pfizer Investigational Site
    • Lakewood, Colorado, United States, 80228
      • Pfizer Investigational Site
    • Littleton, Colorado, United States, 80120
      • Pfizer Investigational Site
    • Lone Tree, Colorado, United States, 80124
      • Pfizer Investigational Site
    • Longmont, Colorado, United States, 80501
      • Pfizer Investigational Site
    • Parker, Colorado, United States, 80138
      • Pfizer Investigational Site
    • Pueblo, Colorado, United States, 81008
      • Pfizer Investigational Site
    • Thorton, Colorado, United States, 80260
      • Pfizer Investigational Site
  • Connecticut
    • Norwich, Connecticut, United States, 06360
      • Pfizer Investigational Site
  • Delaware
    • Newark, Delaware, United States, 19718
      • Pfizer Investigational Site
    • Newark, Delaware, United States, 19713
      • Pfizer Investigational Site
    • Wilmington, Delaware, United States, 19899
      • Pfizer Investigational Site
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Pfizer Investigational Site
    • Delray Beach, Florida, United States, 33484
      • Pfizer Investigational Site
    • Lakeland, Florida, United States, 33805
      • Pfizer Investigational Site
    • Orlando, Florida, United States, 32806
      • Pfizer Investigational Site
  • Georgia
    • Columbus, Georgia, United States, 31902
      • Pfizer Investigational Site
    • Columbus, Georgia, United States, 31904
      • Pfizer Investigational Site
  • Idaho
    • Boise, Idaho, United States, 83712
      • Pfizer Investigational Site
  • Indiana
    • Elkhart, Indiana, United States, 46514
      • Pfizer Investigational Site
    • Jefferson, Indiana, United States, 47130
      • Pfizer Investigational Site
    • Kokomo, Indiana, United States, 46902-3803
      • Pfizer Investigational Site
    • La Porte, Indiana, United States, 46350
      • Pfizer Investigational Site
    • LaPorte, Indiana, United States, 46350
      • Pfizer Investigational Site
    • LaPorte, Indiana, United States, 46350-5533
      • Pfizer Investigational Site
    • Michigan City, Indiana, United States, 46360
      • Pfizer Investigational Site
    • Plymouth, Indiana, United States, 46563
      • Pfizer Investigational Site
    • South Bend, Indiana, United States, 46601
      • Pfizer Investigational Site
    • South Bend, Indiana, United States, 46617
      • Pfizer Investigational Site
  • Iowa
    • Cedar Rapids, Iowa, United States, 52402
      • Pfizer Investigational Site
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Pfizer Investigational Site
    • Lexington, Kentucky, United States, 40536-0293
      • Pfizer Investigational Site
    • Louisville, Kentucky, United States, 40202
      • Pfizer Investigational Site
    • Louisville, Kentucky, United States, 40217
      • Pfizer Investigational Site
    • Louisville, Kentucky, United States, 40207
      • Pfizer Investigational Site
    • Shelbyville, Kentucky, United States, 40065
      • Pfizer Investigational Site
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Pfizer Investigational Site
    • Covington, Louisiana, United States, 70433
      • Pfizer Investigational Site
    • Gretna, Louisiana, United States, 70056
      • Pfizer Investigational Site
    • Marrero, Louisiana, United States, 70072
      • Pfizer Investigational Site
    • Metairie, Louisiana, United States, 70006
      • Pfizer Investigational Site
    • New Orleans, Louisiana, United States, 70115
      • Pfizer Investigational Site
    • Shreveport, Louisiana, United States, 71103
      • Pfizer Investigational Site
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Pfizer Investigational Site
    • Baltimore, Maryland, United States, 21237
      • Pfizer Investigational Site
    • Bethesda, Maryland, United States, 20817
      • Pfizer Investigational Site
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Pfizer Investigational Site
    • Holland, Michigan, United States, 49424
      • Pfizer Investigational Site
    • Niles, Michigan, United States, 49120
      • Pfizer Investigational Site
    • Saint Joseph, Michigan, United States, 49085
      • Pfizer Investigational Site
    • St. Joseph, Michigan, United States, 49085
      • Pfizer Investigational Site
    • St. Joseph, Michigan, United States, 49085-2112
      • Pfizer Investigational Site
    • St. Joseph, Michigan, United States, 49085-2158
      • Pfizer Investigational Site
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Pfizer Investigational Site
    • St. Louis, Missouri, United States, 63141
      • Pfizer Investigational Site
    • Washington, Missouri, United States, 63090
      • Pfizer Investigational Site
  • Nevada
    • Henderson, Nevada, United States, 89052
      • Pfizer Investigational Site
    • Las Vegas, Nevada, United States, 89128
      • Pfizer Investigational Site
    • Las Vegas, Nevada, United States, 89148
      • Pfizer Investigational Site
    • Las Vegas, Nevada, United States, 89135
      • Pfizer Investigational Site
    • Las Vegas, Nevada, United States, 89169
      • Pfizer Investigational Site
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Pfizer Investigational Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131-0001
      • Pfizer Investigational Site
    • Farmington, New Mexico, United States, 87401-5631
      • Pfizer Investigational Site
  • New York
    • Albany, New York, United States, 12206
      • Pfizer Investigational Site
    • Albany, New York, United States, 12208
      • Pfizer Investigational Site
    • Amsterdam, New York, United States, 12010
      • Pfizer Investigational Site
    • Brockport, New York, United States, 14420
      • Pfizer Investigational Site
    • Canadaigua, New York, United States, 14424
      • Pfizer Investigational Site
    • Geneva, New York, United States, 14456
      • Pfizer Investigational Site
    • Hudson, New York, United States, 12534
      • Pfizer Investigational Site
    • Latham, New York, United States, 12110
      • Pfizer Investigational Site
    • New York, New York, United States, 10021
      • Pfizer Investigational Site
    • New York, New York, United States, 10032
      • Pfizer Investigational Site
    • New York, New York, United States, 10022
      • Pfizer Investigational Site
    • Rexford, New York, United States, 12148
      • Pfizer Investigational Site
    • Rochester, New York, United States, 14623
      • Pfizer Investigational Site
    • Rochester, New York, United States, 14626
      • Pfizer Investigational Site
    • Troy, New York, United States, 12180
      • Pfizer Investigational Site
  • North Carolina
    • Cary, North Carolina, United States, 27518
      • Pfizer Investigational Site
    • Clinton, North Carolina, United States, 28328
      • Pfizer Investigational Site
    • Elizabeth City, North Carolina, United States, 27909
      • Pfizer Investigational Site
    • Goldsboro, North Carolina, United States, 27534
      • Pfizer Investigational Site
    • Hickory, North Carolina, United States, 28602
      • Pfizer Investigational Site
    • Raleigh, North Carolina, United States, 27607
      • Pfizer Investigational Site
    • Raleigh, North Carolina, United States, 27614
      • Pfizer Investigational Site
    • Wilson, North Carolina, United States, 27893
      • Pfizer Investigational Site
  • Ohio
    • Canton, Ohio, United States, 44718
      • Pfizer Investigational Site
    • Columbus, Ohio, United States, 43219
      • Pfizer Investigational Site
  • Oklahoma
    • Norman, Oklahoma, United States, 73071
      • Pfizer Investigational Site
    • Oklahoma City, Oklahoma, United States, 73120
      • Pfizer Investigational Site
    • Oklahoma City, Oklahoma, United States, 73102
      • Pfizer Investigational Site
    • Oklahoma City, Oklahoma, United States, 73109
      • Pfizer Investigational Site
    • Oklahoma City, Oklahoma, United States, 73112-4416
      • Pfizer Investigational Site
    • Tulsa, Oklahoma, United States, 74133
      • Pfizer Investigational Site
    • Tulsa, Oklahoma, United States, 74104
      • Pfizer Investigational Site
    • Tulsa, Oklahoma, United States, 74136-1902
      • Pfizer Investigational Site
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Pfizer Investigational Site
    • Springfield, Oregon, United States, 97477
      • Pfizer Investigational Site
  • Pennsylvania
    • Dunmore, Pennsylvania, United States, 18512-3169
      • Pfizer Investigational Site
    • Lemoyne, Pennsylvania, United States, 17043-1440
      • Pfizer Investigational Site
    • Philadelphia, Pennsylvania, United States, 19111-2497
      • Pfizer Investigational Site
    • Scranton, Pennsylvania, United States, 18508
      • Pfizer Investigational Site
  • South Carolina
    • Easley, South Carolina, United States, 29640
      • Pfizer Investigational Site
    • Greenville, South Carolina, United States, 29615
      • Pfizer Investigational Site
    • Greenville, South Carolina, United States, 29605
      • Pfizer Investigational Site
    • Seneca, South Carolina, United States, 29672
      • Pfizer Investigational Site
    • Spartanburg, South Carolina, United States, 29307
      • Pfizer Investigational Site
  • Texas
    • Austin, Texas, United States, 78705
      • Pfizer Investigational Site
    • Austin, Texas, United States, 78745
      • Pfizer Investigational Site
    • Austin, Texas, United States, 78759
      • Pfizer Investigational Site
    • Austin, Texas, United States, 78731
      • Pfizer Investigational Site
    • Austin, Texas, United States, 78758
      • Pfizer Investigational Site
    • Bedford, Texas, United States, 76022
      • Pfizer Investigational Site
    • Corpus Christi, Texas, United States, 78463
      • Pfizer Investigational Site
    • Dallas, Texas, United States, 75230
      • Pfizer Investigational Site
    • Dallas, Texas, United States, 75246
      • Pfizer Investigational Site
    • Fort Worth, Texas, United States, 76177
      • Pfizer Investigational Site
    • Georgetown, Texas, United States, 78626
      • Pfizer Investigational Site
    • Round Rock, Texas, United States, 78681
      • Pfizer Investigational Site
    • San Antonio, Texas, United States, 78229
      • Pfizer Investigational Site
    • San Antonio, Texas, United States, 78207
      • Pfizer Investigational Site
    • San Antonio, Texas, United States, 78217
      • Pfizer Investigational Site
    • San Antonio, Texas, United States, 78258
      • Pfizer Investigational Site
    • Tyler, Texas, United States, 75702
      • Pfizer Investigational Site
    • Webster, Texas, United States, 77598
      • Pfizer Investigational Site
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Pfizer Investigational Site
  • Virginia
    • Chesapeake, Virginia, United States, 23320
      • Pfizer Investigational Site
    • Hampton, Virginia, United States, 23666
      • Pfizer Investigational Site
    • Newport News, Virginia, United States, 23601
      • Pfizer Investigational Site
    • Newport News, Virginia, United States, 23502
      • Pfizer Investigational Site
    • Norfolk, Virginia, United States, 23502
      • Pfizer Investigational Site
    • Virginia Beach, Virginia, United States, 23456
      • Pfizer Investigational Site
    • Williamsburg, Virginia, United States, 23188
      • Pfizer Investigational Site
  • Washington
    • Seattle, Washington, United States, 98195
      • Pfizer Investigational Site
    • Seattle, Washington, United States, 98109
      • Pfizer Investigational Site
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • Pfizer Investigational Site
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Pfizer Investigational 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:

• Advanced renal cell carcinoma of clear cell origin or a component of clear cell histology.
• Measurable disease

Exclusion Criteria:

• Prior systemic therapy of any kind for advanced renal cell cancer
• History of brain metastases
• Uncontrolled hypertension

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A	Drug: Sunitinib Malate Schedule 4/2; Sunitinib malate starting dose 50 mg per day for four weeks, followed by a two week off-drug period. This six week cycle is repeated.
Experimental: C	Drug: Sunitinib Malate Continuous Daily Dosing; Sunitinib malate starting dose 37.5 mg daily continuous daily regimen.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Tumor Progression (TTP) Assessed Using Memorial Sloan-Kettering Cancer Center (MSKCC) Prognostic Factors Model	MSKCC Prognostic Factor Model assessed as low(0),intermediate(1-2) or high(=>3) based on number of criteria present such as Karnofsky performance status < 80 %, Lactate dehydrogenase > 1.5 * Upper limit of Normal,Hemoglobin < lower limit of normal, serum calcium > 10 mg/dL;Time from first diagnosis of renal cell carcinoma to start of systemic therapy of < 1 year.TTP was time from start of study treatment to first documentation of objective tumor progression or death due to cancer.TTP was calculated as (first event date minus date of first dose of study medication plus 1) divided by 30.44.	From date of randomization until the date of first documented progression or date of death due to any cause, assessed up to a maximum of 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Objective Response (OR)	Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. CR are defined as the disappearance of all lesions (target and/or non target). PR are those with atleast 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.	From date of randomization until the date of first documented progression or date of death due to any cause, assessed up to a maximum of 2 years
Duration of Response (DR)	Time from the first documentation of objective tumor response to objective tumor progression or death due to any cause. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 30.44. DR was calculated for the subgroup of participants with a confirmed objective tumor response.	From date of randomization until the date of first documented progression or date of death due to any cause, assessed up to a maximum of 2 years
Overall Survival (OS) Assessed Using MSKCC Prognostic Factors Model	MSKCC Prognostic Factor Model assessed as low (0), intermediate (1-2) or high (=>3) based upon number of criteria present. Criteria as follows: Karnofsky performance status < 80 %, Lactate dehydrogenase > 1.5 * Upper limit of Normal, Hemoglobin < lower limit of normal for local lab, Corrected serum calcium > 10 mg/dL; Time from first diagnosis of renal cell carcinoma to start of systemic therapy of < 1 year. OS was defined as time from date of start of treatment to date of death due to any cause. OS, in months, was calculated as (event date -start of treatment date + 1)/30.44.	From date of randomization until the date of first documented progression or date of death due to any cause, assessed up to a maximum of 2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional Assessment of Cancer Therapy-General (FACT-G)	FACT-G is core questionnaire of Functional Assessment of Chronic Illness Therapy (FACIT) measurement system to evaluate quality of life (QoL) in cancer population.FACT-G consisted of 27 questions grouped in 4 domains of general Health-Related QoL(HRQoL):Physical Well-being(PWB),Social/Family Well-Being (SWB),Emotional Well-Being (EWB) and Functional Well-Being (FWB);each ranging from 0 (not at all) to 4 (very much) so that FACT-G ranged between 0-108.Since questions could be reversed coded, as appropriate, before calculating FACT-G,0 and 108 could be considered worst and best health states.	From date of randomization until the date of first documented progression or date of death due to any cause, assessed up to a maximum of 2 years
FACT-Kidney Symptom Index for Disease Related Symptoms (FKSI-DRS)	FKSI-DRS is a subset of FKSI which is a questionnaire for Functional Assessment of Cancer Therapy -Kidney Symptom Index used to assess QoL/participant-reported outcomes for participants diagnosed with renal cell cancer. The FKSI contained 15 questions and the FKSI-DRS consisted of 9 questions each ranging from 0 (not at all) to 4 (very much) so that FKSI-DRS ranged between 0-36. Since the questions could be reversed coded, as appropriate, before calculating FKSI-DRS, 0 and 36 could be considered the worst and best health states based on the 9 questions comprising FKSI-DRS.	From date of randomization until the date of first documented progression or date of death due to any cause, assessed up to a maximum of 2 years

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.
• Motzer RJ, Hutson TE, Hudes GR, Figlin RA, Martini JF, English PA, Huang X, Valota O, Williams JA. Investigation of novel circulating proteins, germ line single-nucleotide polymorphisms, and molecular tumor markers as potential efficacy biomarkers of first-line sunitinib therapy for advanced renal cell carcinoma. Cancer Chemother Pharmacol. 2014 Oct;74(4):739-50. doi: 10.1007/s00280-014-2539-0. Epub 2014 Aug 7.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: December 1, 2005
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: December 20, 2005
• First Submitted That Met QC Criteria: December 20, 2005
• First Posted (Estimate): December 21, 2005

Study Record Updates

• Last Update Posted (Estimate): September 5, 2011
• Last Update Submitted That Met QC Criteria: August 3, 2011
• Last Verified: August 1, 2011

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: A6181065