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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

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.

Condition or disease Intervention/treatment Phase
Breast Neoplasms Drug: SU011248 Drug: Chemotherapy Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 217 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : January 2006
Actual Primary Completion Date : May 2010
Actual Study Completion Date : June 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: A 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

Active Comparator: B 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.




Primary Outcome Measures :
  1. 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").


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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).

  5. 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.

  6. 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.

  7. 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 ]
  8. 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 ]
  9. 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 ]
  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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.

  19. 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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00246571


  Show 113 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00246571     History of Changes
Other Study ID Numbers: A6181077
First Posted: October 31, 2005    Key Record Dates
Results First Posted: June 27, 2011
Last Update Posted: July 12, 2012
Last Verified: July 2012

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Sunitinib
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors