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Study Of SU011248 Versus Chemotherapy For Patients With Previously Treated Triple Receptor Negative Breast Cancer

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ClinicalTrials.gov Identifier: NCT00246571
Recruitment Status : Completed
First Posted : October 31, 2005
Results First Posted : June 27, 2011
Last Update Posted : July 12, 2012
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE October 27, 2005
First Posted Date  ICMJE October 31, 2005
Results First Submitted Date  ICMJE May 31, 2011
Results First Posted Date  ICMJE June 27, 2011
Last Update Posted Date July 12, 2012
Study Start Date  ICMJE January 2006
Actual Primary Completion Date May 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 31, 2011)
Progression-Free Survival (PFS) [ Time Frame: Baseline, every 6 weeks until disease progression or death (up to 3 years from first dose) ]
Time in months from start of study treatment to first documentation of objective tumor progression (per RECIST) or death due to any cause. PFS was calculated as (first event date minus first randomization date plus 1) divided by 30.4. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from adverse event (AE) data (where the outcome was "Death").
Original Primary Outcome Measures  ICMJE
 (submitted: October 27, 2005)
Progression-free-survival
Change History Complete list of historical versions of study NCT00246571 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 15, 2012)
  • Proportion of Participants With Objective Response [ Time Frame: Baseline until response or disease progression (up to 3 years from first dose) ]
    Objective response based assessment of confirmed response (CR) or confirmed partial response (PR) according to RECIST. CR are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. PR are those with a greater than or equal to (≥) 30% decrease in the sum of the longest dimensions (SLD) of the target lesions taking as a reference the baseline SLD.
  • Duration of Response (DR) [ Time Frame: Time from first response to disease progression up to 3 years from first dose ]
    Time in months from the first documentation of objective tumor response (CR or PR) to objective tumor progression or death. 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 30.4. DR was calculated for the subgroup of participants with a confirmed objective tumor response.
  • Survival Probability at 1 Year [ Time Frame: Baseline until death (up to 3 years after first dose of study medication) ]
    Probability that the participants will survive at end of 1 year from the first dose of study treatment. Calculated using data collected from baseline until death (up to 3 years after first dose of study medication). Probability calculated from Kaplan-Meier estimate.
  • Overall Survival (OS) [ Time Frame: Baseline until death (up to 3 years after first dose of study medication) ]
    Time in months from the date of randomization to date of death due to any cause. OS was calculated as (date of death minus randomization date plus 1) divided by 30.4. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death).
  • Health Related Quality of Life (HRQoL) and Disease Related Symptoms as Measured by European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (EORTC-QLQ-C30) [ Time Frame: Day 1, Cycle 1; Day 1, odd number cycles; and end of treatment (EOT)/withdrawal ]
    EORTC QLQ-C30: global health/QoL, functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much; global/QoL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms.
  • HRQoL and Disease Related Symptoms as Measured by EORTC-QLQ-C30 Breast Cancer Module (BR23) Score [ Time Frame: Day 1, Cycle 1; Day 1, odd number cycles; and EOT/withdrawal ]
    BR23: measured disease related symptoms of dry mouth, eye pain, hair loss, hot flushes, attractiveness, future health, sexual activity, arm/shoulder pain, breast pain, swollen breast, and skin problems on the breast. Recall period: past week; response range: not at all to very much. Scale score range: 0 to 100. Higher symptom score = greater degree of symptoms.
  • Observed Plasma Trough Concentrations (Ctrough) of Sunitinib [ Time Frame: Predose Day 1, Cycles 1, 2, 3, 4, 5 and 7 and Day 15 of Cycles 1, 2, and 3 ]
  • Ctrough of SU012662 (Metabolite of Sunitinib) [ Time Frame: Predose Day 1, Cycles 1, 2, 3, 4, 5 and 7 and Day 15 of Cycles 1, 2, and 3 ]
  • Ctrough of Total Drug (Sunitinib + SU012662) [ Time Frame: Predose Day 1, Cycles 1, 2, 3, 4, 5 and 7 and Day 15 of Cycles 1, 2, and 3 ]
  • Dose-corrected Ctrough of Sunitinib [ Time Frame: Predose Day 1, Cycles 1, 2, 3, 4, 5 and 7 and Day 15 of Cycles 1, 2, and 3 ]
    Ctrough = plasma concentration of sunitinib prior to study drug administration, dose corrected using the following formula Intended Dose/Actual Dose, where Actual Dose: the dose the participant received over the last 10 consecutive days and Intended Dose: the starting dose per study protocol.
  • Dose-corrected Ctrough of SU012662 (Metabolite of Sunitinib) [ Time Frame: Predose Day 1, Cycles 1, 2, 3, 4, 5 and 7 and Day 15 of Cycles 1, 2, and 3 ]
    Ctrough = plasma concentration of SU012662 prior to study drug administration, dose corrected using the following formula Intended Dose/Actual Dose, where Actual Dose: the dose the participant received over the last 10 consecutive days and Intended Dose: the starting dose per study protocol.
  • Dose-corrected Ctrough of Total Drug (Sunitinib + SU012662) [ Time Frame: Predose Day 1, Cycles 1, 2, 3, 4, 5 and 7 and Day 15 of Cycles 1, 2, and 3 ]
    Ctrough = plasma concentration of total drug (Sunitinib + SU012662) prior to study drug administration dose corrected using the following formula Intended Dose/Actual Dose, where Actual Dose: the dose the participant received over the last 10 consecutive days and Intended Dose: the starting dose per study protocol.
  • Plasma Concentration of Soluble Vascular Endothelial Growth Factor Receptor 2 (sVEGFR2) [ Time Frame: Baseline (Cycle 1, Day 1), Day 1 (Cycles 2, 3, 4, 5, and 7), and EOT/withdrawal ]
    Plasma concentrations of sVEGFR2 were examined as a potential pharmacodynamic marker
  • Plasma Concentration of Soluble Vascular Endothelial Growth Factor Receptor 3 (sVEGFR3) [ Time Frame: Baseline (Cycle 1, Day 1), Day 1 (Cycles 2, 3, 4, 5, and 7), and EOT/withdrawal ]
    Plasma concentrations of sVEGFR3 were examined as a potential pharmacodynamic marker
  • Plasma Concentration of Soluble Vascular Endothelial Growth Factor A (sVEGF-A) [ Time Frame: Baseline (Cycle 1, Day 1), Day 1 (Cycles 2, 3, 4, 5, and 7), and EOT/withdrawal ]
    Plasma concentrations of sVEGF-A were examined as a potential pharmacodynamic marker
  • Plasma Concentration of Soluble Placental Growth Factor (sPlGF) [ Time Frame: Baseline (Cycle 1, Day 1), Day 1 (Cycles 2, 3, 4, 5 and 7), and EOT/withdrawal ]
    Plasma concentrations of sPlGF were examined as a potential pharmacodynamic marker
  • Plasma Concentration of Soluble Kinase Insert Domain for Tyrosine (sKIT), a Stem Cell Factor Receptor [ Time Frame: Baseline (Cycle 1, Day 1), Day 1 (Cycles 2, 3, 4, 5 and 7), and EOT/withdrawal ]
    Plasma concentrations of sKIT were examined as a potential pharmacodynamic marker
  • Circulating Endothelial Cells (CEC) [ Time Frame: Days 1 and 15 of Cycles 1, 2 and 3, Day 1 of Cycles 4 and 5, and every odd cycle thereafter, and EOT/withdrawal ]
    Blood samples were collected to enumerate the number of total CECs and sVEGFR1, sVEGFR2 and sVEGFR3 protein expression and/or cellular viability.
  • Circulating Tumor Cells (CTC) [ Time Frame: Days 1 and 15 of Cycles 1, 2 and 3, Day 1 of Cycles 4 and 5, and every odd cycle thereafter, and EOT/withdrawal ]
    Blood samples were collected to enumerate the number of total CTCs and insulin growth factor 1R positive (IGF-1R+) CTCs
Original Secondary Outcome Measures  ICMJE
 (submitted: October 27, 2005)
Objective response rate; Duration of response; Overall survival; One year survival; Patient reported outcomes of health related quality of life and disease related symptoms
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study Of SU011248 Versus Chemotherapy For Patients With Previously Treated Triple Receptor Negative Breast Cancer
Official Title  ICMJE A Randomized Phase 2 Study Of SU011248 Versus Standard-Of-Care For Patients With Previously Treated, Advanced, Triple Receptor Negative (ER, PR, HER2) Breast Cancer
Brief Summary The purpose of this study is to compare progression free survival for SU011248 [sutent (sunitinib malate)] versus standard of care therapy in patients with previously treated, advanced, triple receptor negative (ER, PR, HER2) locally recurrent or metastatic breast cancer.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Neoplasms
Intervention  ICMJE
  • Drug: SU011248
    SU011248 capsules administered orally, daily in a continuous regimen, 3-week cycles, starting dose of 37.5 mg daily. 1-week treatment rests and dose reductions allowed for dose-limiting toxicity. Dose escalate SU011248 to 50-mg daily if minimal toxicities . Study will continue until disease progression. Patients randomized to or crossed over to SU011248 may continue beyond the time of Response Evaluation Criterion in Solid Tumors (RECIST) -defined progression at the discretion of the investigator in the case of clinical benefit.
    Other Name: Sutent, sunitinib malate
  • Drug: Chemotherapy

    The choice of chemotherapy will be at the discretion of the investigator within the limits outlined below.

    1. Capecitabine - 1000-1250 mg/m2 twice daily days 1-14 every 3 weeks
    2. Vinorelbine - 25-30 mg/m2 rapid intravenous infusion or 60-80 mg/m2 oral weekly, expressed in 3-week cycles
    3. Docetaxel - 75-100 mg/m2 every 3 weeks
    4. Paclitaxel - 175-200 mg/m2 every 3 weeks
    5. Paclitaxel - 80-90 mg/m2 weekly, in a continuous regimen expressed in 3-week cycles or administration of 3 weeks of treatment followed by 1 week of rest. Use of the 3/1 regimen will require extra care in scheduling disease assessments.
    6. Gemcitabine - 800-1250 mg/m2 Days 1 and 8 every 3 weeks Study will continue until disease progression or it is in the best interest of the patient to discontinue based on achievement of maximum benefit or tolerability issues. At the time of progression patients randomized to chemotherapy will be offered crossover to single agent SU011248.
Study Arms  ICMJE
  • Experimental: A
    Intervention: Drug: SU011248
  • Active Comparator: B
    Intervention: Drug: Chemotherapy
Publications * Curigliano G, Pivot X, Cortés J, Elias A, Cesari R, Khosravan R, Collier M, Huang X, Cataruozolo PE, Kern KA, Goldhirsch A. Randomized phase II study of sunitinib versus standard of care for patients with previously treated advanced triple-negative breast cancer. Breast. 2013 Oct;22(5):650-6. doi: 10.1016/j.breast.2013.07.037. Epub 2013 Aug 17.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 16, 2011)
217
Original Enrollment  ICMJE
 (submitted: October 27, 2005)
200
Actual Study Completion Date  ICMJE June 2011
Actual Primary Completion Date May 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Recurrent or metastatic breast cancer
  • Estrogen receptor (ER), progestin receptor (PR) and HER2/neu receptor (HER2) negative status
  • Prior treatment with an anthracycline and a taxane in the adjuvant or advanced disease setting
  • Relapse following adjuvant chemotherapy within 6 months of last treatment and/or received one or two chemotherapy regimens for advanced disease

Exclusion Criteria:

  • More than two chemotherapy regimens for advanced disease
  • Uncontrolled/symptomatic spread of cancer to the brain
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Bulgaria,   Canada,   Czech Republic,   France,   Germany,   Hungary,   Italy,   Spain,   Turkey,   Ukraine,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00246571
Other Study ID Numbers  ICMJE A6181077
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date July 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP