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

• ClinicalTrials.gov Identifier: NCT00267748
• Recruitment Status: Completed
• First Posted: December 21, 2005
• Results First Posted: September 5, 2011
• Last Update Posted: September 5, 2011
• Sponsor: Pfizer
• Information provided by: Pfizer

Tracking Information

• First Submitted Date: December 20, 2005
• First Posted Date: December 21, 2005
• Results First Submitted Date: June 23, 2011
• Results First Posted Date: September 5, 2011
• Last Update Posted Date: September 5, 2011
• Study Start Date: December 2005
• Actual Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 3, 2011)

Time to Tumor Progression (TTP) Assessed Using Memorial Sloan-Kettering Cancer Center (MSKCC) Prognostic Factors Model [ Time Frame: 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 ]

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.

• Original Primary Outcome Measures (submitted: December 20, 2005): The primary objective for the randomized part of the trial is to compare the time to progression for sunitinib malate when given on Schedule 4/2 alone and in combination with interferon alfa-2b.

Current Secondary Outcome Measures (submitted: August 3, 2011)

• Percentage of Participants With Objective Response (OR) [ Time Frame: 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 ]
  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.
• Duration of Response (DR) [ Time Frame: 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 ]
  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.
• Overall Survival (OS) Assessed Using MSKCC Prognostic Factors Model [ Time Frame: 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 ]
  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.

• Original Secondary Outcome Measures (submitted: December 20, 2005): Secondary objectives: Evaluate safety and tolerability, time to progression, response rate, overall survival and quality of life of sunitinib malate when given in two dose schedules and in combination with interferon alfa-2b.

Current Other Pre-specified Outcome Measures (submitted: August 3, 2011)

• Functional Assessment of Cancer Therapy-General (FACT-G) [ Time Frame: 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-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.
• FACT-Kidney Symptom Index for Disease Related Symptoms (FKSI-DRS) [ Time Frame: 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 ]
  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.

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

Brief Summary

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Carcinoma, Renal Cell

Intervention

• Drug: Sunitinib Malate Continuous Daily Dosing
  Sunitinib malate starting dose 37.5 mg daily continuous daily regimen.
• 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.

Study Arms

• Experimental: C
  Intervention: Drug: Sunitinib Malate Continuous Daily Dosing
• Experimental: A
  Intervention: Drug: Sunitinib Malate Schedule 4/2

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 6, 2011): 317
• Original Enrollment (submitted: December 20, 2005): 499
• Actual Study Completion Date: June 2010
• Actual Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00267748
• Other Study ID Numbers: A6181065
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer Inc
• Original Responsible Party: Not Provided
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: August 2011