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

Breast Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00246571
• Other study ID #: A6181077
• Status: Completed
• Phase: Phase 2
• First received: October 27, 2005
• Last updated: July 2, 2012
• Start date: January 2006
• Est. completion date: June 2011

Study information

• Verified date: July 2012
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 217
• Est. completion date: June 2011
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms

Intervention

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.
• Chemotherapy
The choice of chemotherapy will be at the discretion of the investigator within the limits outlined below. Capecitabine - 1000-1250 mg/m2 twice daily days 1-14 every 3 weeks Vinorelbine - 25-30 mg/m2 rapid intravenous infusion or 60-80 mg/m2 oral weekly, expressed in 3-week cycles Docetaxel - 75-100 mg/m2 every 3 weeks Paclitaxel - 175-200 mg/m2 every 3 weeks 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. 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.

Locations

Country	Name	City	State
Bulgaria	Pfizer Investigational Site	Sofia
Bulgaria	Pfizer Investigational Site	Sofia
Bulgaria	Pfizer Investigational Site	Sofia
Bulgaria	Pfizer Investigational Site	Stara Zagora
Bulgaria	Pfizer Investigational Site	Varna
Canada	Pfizer Investigational Site	Edmonton	Alberta
Canada	Pfizer Investigational Site	Toronto	Ontario
Czech Republic	Pfizer Investigational Site	Brno	Ceska Republika
Czech Republic	Pfizer Investigational Site	Brno
Czech Republic	Pfizer Investigational Site	Praha 8
Czech Republic	Pfizer Investigational Site	Praha 8	Ceska Republika
France	Pfizer Investigational Site	BESANCON cedex
France	Pfizer Investigational Site	BESANCON Cedex 5
France	Pfizer Investigational Site	NANTES cedex
France	Pfizer Investigational Site	Paris Cedex 20
Germany	Pfizer Investigational Site	Berlin
Hungary	Pfizer Investigational Site	Budapest
Hungary	Pfizer Investigational Site	Budapest
Italy	Pfizer Investigational Site	Aviano (PN)
Italy	Pfizer Investigational Site	Milano
Italy	Pfizer Investigational Site	Prato, FI
Spain	Pfizer Investigational Site	Barcelona
Spain	Pfizer Investigational Site	Gerona
Spain	Pfizer Investigational Site	Lleida
Spain	Pfizer Investigational Site	Malaga
Spain	Pfizer Investigational Site	Sevilla
Turkey	Pfizer Investigational Site	Adana	Balcali
Turkey	Pfizer Investigational Site	Ankara	Besevler
Turkey	Pfizer Investigational Site	Ankara	Sihhiye
Turkey	Pfizer Investigational Site	Istanbul	Pendik
Ukraine	Pfizer Investigational Site	Dnipropetrovsk
Ukraine	Pfizer Investigational Site	Kyiv
Ukraine	Pfizer Investigational Site	Odessa
United Kingdom	Pfizer Investigational Site	Edinburgh
United Kingdom	Pfizer Investigational Site	Oxfordshire
United Kingdom	Pfizer Investigational Site	Southampton
United States	Pfizer Investigational Site	Atlanta	Georgia
United States	Pfizer Investigational Site	Atlanta	Georgia
United States	Pfizer Investigational Site	Aurora	Colorado
United States	Pfizer Investigational Site	Biloxi	Mississippi
United States	Pfizer Investigational Site	Bloomfield Hills	Michigan
United States	Pfizer Investigational Site	Boca Raton	Florida
United States	Pfizer Investigational Site	Bronx	New York
United States	Pfizer Investigational Site	Bronx	New York
United States	Pfizer Investigational Site	Brownstown	Michigan
United States	Pfizer Investigational Site	Clarkson Valley	Missouri
United States	Pfizer Investigational Site	Clinton	North Carolina
United States	Pfizer Investigational Site	Corona	California
United States	Pfizer Investigational Site	Dallas	Texas
United States	Pfizer Investigational Site	Dallas	Texas
United States	Pfizer Investigational Site	Dearborn	Michigan
United States	Pfizer Investigational Site	Decatur	Georgia
United States	Pfizer Investigational Site	Del City	Oklahoma
United States	Pfizer Investigational Site	Detroit	Michigan
United States	Pfizer Investigational Site	Federal Way	Washington
United States	Pfizer Investigational Site	Fort Worth	Texas
United States	Pfizer Investigational Site	Fullerton	California
United States	Pfizer Investigational Site	Gainesville	Florida
United States	Pfizer Investigational Site	Glendora	California
United States	Pfizer Investigational Site	Goldsboro	North Carolina
United States	Pfizer Investigational Site	Greensburg	Pennsylvania
United States	Pfizer Investigational Site	Hershey	Pennsylvania
United States	Pfizer Investigational Site	Houston	Texas
United States	Pfizer Investigational Site	Houston	Texas
United States	Pfizer Investigational Site	Indianapolis	Indiana
United States	Pfizer Investigational Site	Lakewood	Washington
United States	Pfizer Investigational Site	Los Angeles	California
United States	Pfizer Investigational Site	Los Angeles	California
United States	Pfizer Investigational Site	Los Angeles	California
United States	Pfizer Investigational Site	Macon	Georgia
United States	Pfizer Investigational Site	Marietta	Georgia
United States	Pfizer Investigational Site	Memphis	Tennessee
United States	Pfizer Investigational Site	Memphis	Tennessee
United States	Pfizer Investigational Site	Memphis	Tennessee
United States	Pfizer Investigational Site	Midland Park	New Jersey
United States	Pfizer Investigational Site	Mission Hills	California
United States	Pfizer Investigational Site	Morristown	New Jersey
United States	Pfizer Investigational Site	Northridge	California
United States	Pfizer Investigational Site	Palm Springs	California
United States	Pfizer Investigational Site	Paramus	New Jersey
United States	Pfizer Investigational Site	Pasadena	California
United States	Pfizer Investigational Site	Pittsburgh	Pennsylvania
United States	Pfizer Investigational Site	Pittsburgh	Pennsylvania
United States	Pfizer Investigational Site	Plano	Texas
United States	Pfizer Investigational Site	Plano	Texas
United States	Pfizer Investigational Site	Pomona	California
United States	Pfizer Investigational Site	Pompton Plains	New Jersey
United States	Pfizer Investigational Site	Puyallup	Washington
United States	Pfizer Investigational Site	Rancho Cucamonga	California
United States	Pfizer Investigational Site	Richardson	Texas
United States	Pfizer Investigational Site	Ridgewood	New Jersey
United States	Pfizer Investigational Site	San Antonio	Texas
United States	Pfizer Investigational Site	San Antonio	Texas
United States	Pfizer Investigational Site	San Antonio	Texas
United States	Pfizer Investigational Site	San Antonio	Texas
United States	Pfizer Investigational Site	San Atonio	Texas
United States	Pfizer Investigational Site	Santa Monica	California
United States	Pfizer Investigational Site	Seattle	Washington
United States	Pfizer Investigational Site	Seattle	Washington
United States	Pfizer Investigational Site	St. Louis	Missouri
United States	Pfizer Investigational Site	St. Louis	Missouri
United States	Pfizer Investigational Site	Summit	New Jersey
United States	Pfizer Investigational Site	Tacoma	Washington
United States	Pfizer Investigational Site	Tucker	Georgia
United States	Pfizer Investigational Site	Tyler	Texas
United States	Pfizer Investigational Site	Valencia	California
United States	Pfizer Investigational Site	Washington	District of Columbia
United States	Pfizer Investigational Site	West Bloomfield	Michigan
United States	Pfizer Investigational Site	West Covina	California
United States	Pfizer Investigational Site	Westwood	New Jersey
United States	Pfizer Investigational Site	Wexford	Pennsylvania
United States	Pfizer Investigational Site	Wilson	North Carolina
United States	Pfizer Investigational Site	Zion	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Bulgaria,  Canada,  Czech Republic,  France,  Germany,  Hungary,  Italy,  Spain,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS)	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").	Baseline, every 6 weeks until disease progression or death (up to 3 years from first dose)	No
Secondary	Proportion of Participants With Objective Response	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.	Baseline until response or disease progression (up to 3 years from first dose)	No
Secondary	Duration of Response (DR)	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.	Time from first response to disease progression up to 3 years from first dose	No
Secondary	Survival Probability at 1 Year	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.	Baseline until death (up to 3 years after first dose of study medication)	No
Secondary	Overall Survival (OS)	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).	Baseline until death (up to 3 years after first dose of study medication)	No
Secondary	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)	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.	Day 1, Cycle 1; Day 1, odd number cycles; and end of treatment (EOT)/withdrawal	No
Secondary	HRQoL and Disease Related Symptoms as Measured by EORTC-QLQ-C30 Breast Cancer Module (BR23) Score	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.	Day 1, Cycle 1; Day 1, odd number cycles; and EOT/withdrawal	No
Secondary	Observed Plasma Trough Concentrations (Ctrough) of Sunitinib		Predose Day 1, Cycles 1, 2, 3, 4, 5 and 7 and Day 15 of Cycles 1, 2, and 3	No
Secondary	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	No
Secondary	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	No
Secondary	Dose-corrected Ctrough of Sunitinib	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.	Predose Day 1, Cycles 1, 2, 3, 4, 5 and 7 and Day 15 of Cycles 1, 2, and 3	No
Secondary	Dose-corrected Ctrough of SU012662 (Metabolite of Sunitinib)	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.	Predose Day 1, Cycles 1, 2, 3, 4, 5 and 7 and Day 15 of Cycles 1, 2, and 3	No
Secondary	Dose-corrected Ctrough of Total Drug (Sunitinib + SU012662)	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.	Predose Day 1, Cycles 1, 2, 3, 4, 5 and 7 and Day 15 of Cycles 1, 2, and 3	No
Secondary	Plasma Concentration of Soluble Vascular Endothelial Growth Factor Receptor 2 (sVEGFR2)	Plasma concentrations of sVEGFR2 were examined as a potential pharmacodynamic marker	Baseline (Cycle 1, Day 1), Day 1 (Cycles 2, 3, 4, 5, and 7), and EOT/withdrawal	No
Secondary	Plasma Concentration of Soluble Vascular Endothelial Growth Factor Receptor 3 (sVEGFR3)	Plasma concentrations of sVEGFR3 were examined as a potential pharmacodynamic marker	Baseline (Cycle 1, Day 1), Day 1 (Cycles 2, 3, 4, 5, and 7), and EOT/withdrawal	No
Secondary	Plasma Concentration of Soluble Vascular Endothelial Growth Factor A (sVEGF-A)	Plasma concentrations of sVEGF-A were examined as a potential pharmacodynamic marker	Baseline (Cycle 1, Day 1), Day 1 (Cycles 2, 3, 4, 5, and 7), and EOT/withdrawal	No
Secondary	Plasma Concentration of Soluble Placental Growth Factor (sPlGF)	Plasma concentrations of sPlGF were examined as a potential pharmacodynamic marker	Baseline (Cycle 1, Day 1), Day 1 (Cycles 2, 3, 4, 5 and 7), and EOT/withdrawal	No
Secondary	Plasma Concentration of Soluble Kinase Insert Domain for Tyrosine (sKIT), a Stem Cell Factor Receptor	Plasma concentrations of sKIT were examined as a potential pharmacodynamic marker	Baseline (Cycle 1, Day 1), Day 1 (Cycles 2, 3, 4, 5 and 7), and EOT/withdrawal	No
Secondary	Circulating Endothelial Cells (CEC)	Blood samples were collected to enumerate the number of total CECs and sVEGFR1, sVEGFR2 and sVEGFR3 protein expression and/or cellular viability.	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	No
Secondary	Circulating Tumor Cells (CTC)	Blood samples were collected to enumerate the number of total CTCs and insulin growth factor 1R positive (IGF-1R+) CTCs	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	No

External Links

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