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

Phase 2
Completed
Conditions
Breast Neoplasms
Interventions
Drug: SU011248
Drug: Chemotherapy
Registration Number
NCT00246571
Lead Sponsor
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
217
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
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Exclusion Criteria
  • More than two chemotherapy regimens for advanced disease
  • Uncontrolled/symptomatic spread of cancer to the brain
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
ASU011248-
BChemotherapy-
Primary Outcome Measures
NameTimeMethod
Progression-Free Survival (PFS)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
NameTimeMethod
Proportion of Participants With Objective ResponseBaseline 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 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 YearBaseline 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)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)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) ScoreDay 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 SunitinibPredose 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)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)Predose Day 1, Cycles 1, 2, 3, 4, 5 and 7 and Day 15 of Cycles 1, 2, and 3
Dose-corrected Ctrough of SunitinibPredose 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)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)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)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)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)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)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 ReceptorBaseline (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)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)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

Trial Locations

Locations (1)

Pfizer Investigational Site

🇬🇧

Southampton, United Kingdom

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