A RANDOMIZED PHASE 2 STUDY OF SU011248 VERSUS STANDARD-OF-CARE FOR PATIENTS WITH PREVIOUSLY TREATED, ADVANCED, TRIPLE RECEPTOR NEGATIVE (ER, PR, AND HER2) BREAST CANCER Estudio aleatorizado en Fase 2 de SU011248 frente al tratamiento estándar en pacientes con cáncer de mama avanzado, tratados previamente y con triple receptor negativo (ER, PR y HER2)

• Register: EUCTR
• Last refreshed on: 18 April 2012
• Main ID: EUCTR2005-003774-15-ES
• Date of registration: 10/11/2005
• Prospective Registration: Yes
• Primary sponsor: Pfizer, S.A.
• Public title: A RANDOMIZED PHASE 2 STUDY OF SU011248 VERSUS STANDARD-OF-CARE FOR PATIENTS WITH PREVIOUSLY TREATED, ADVANCED, TRIPLE RECEPTOR NEGATIVE (ER, PR, AND HER2) BREAST CANCER Estudio aleatorizado en Fase 2 de SU011248 frente al tratamiento estándar en pacientes con cáncer de mama avanzado, tratados previamente y con triple receptor negativo (ER, PR y HER2)
• Scientific title: A RANDOMIZED PHASE 2 STUDY OF SU011248 VERSUS STANDARD-OF-CARE FOR PATIENTS WITH PREVIOUSLY TREATED, ADVANCED, TRIPLE RECEPTOR NEGATIVE (ER, PR, AND HER2) BREAST CANCER Estudio aleatorizado en Fase 2 de SU011248 frente al tratamiento estándar en pacientes con cáncer de mama avanzado, tratados previamente y con triple receptor negativo (ER, PR y HER2)
• Date of first enrolment: 26/12/2005
• Target sample size: 200
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-003774-15
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Best supportive care

Countries of recruitment

Bulgaria, Czech Republic, Germany, Hungary, Italy, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Histologically or cytologically proven diagnosis of breast cancer with evidence of 1)
unresectable, locally recurrent, or 2) metastatic disease. Locally recurrent
disease must not be amenable to resection or radiation therapy with curative
intent.
2. Documentation of estrogen and progestin receptor (ER/PR) negative status and
HER2/neu receptor negative status (ie, FISH negative or immunohistochemistry 0
or +1).
3. Prior treatment with an anthracycline and a taxane in the adjuvant or metastatic
disease setting.
4. Prior treatment with chemotherapy as follows:
• Receipt of adjuvant chemotherapy with RECIST or World Health Organization
(WHO)-defined disease progression documented during treatment or disease
relapse within 6 months of last treatment, OR
• Receipt of chemotherapy in the first-line advanced disease setting with RECIST
or WHO-defined disease progression documented during treatment, or, if the
patient completed treatment with objective disease response, disease
progression documented within 3 months after discontinuing treatment.
Patients entering the study on the basis of this criterion may have also
previously received adjuvant treatment with chemotherapy.
5. Measurable disease as per RECIST. Measurable lesions that have been
previously radiated will not be considered target lesions unless increase in size
has been observed following completion of radiation therapy.
6. Candidate for treatment with one of the standard chemotherapy regimens
listed if patient is randomized to the control arm. Safety precautions standard
for specific chemotherapy regimens but not stated in study entry criteria must
be ensured by the investigator prior to randomization. Examples include
precautions for some chemotherapy regimens based on moderately elevated
liver function tests and prior hypersensitivity to an agent.
7. Patients receiving bisphosphonate therapy for metastatic bone disease must
have initiated therapy at least 4 weeks prior to first dose of treatment on study.
8. Male or Female, 18 years of age or older.
9. ECOG performance status 0 or 1.
10. Resolution of all acute toxic effects of prior therapy or surgical procedures to
grade less tha/equal to 1 (except alopecia).
11. The definitions of minimum adequacy for organ function required prior to study
entry are as follows. In addition, safety precautions provided in the product
labeling for the anticipated control arm chemotherapy must be observed.
• Serum aspartate transaminase (AST) and serum alanine transaminase
(ALT) less than/equal to 2.5 x upper limit of normal (ULN), or AST and ALT less
than/equal to 5 x ULN if liver function abnormalities are due to underlying
malignancy
• Total serum bilirubin less than/equal to 1.5 x ULN
• Serum albumin major than/equal to 3.0 g/dL
• Absolute neutrophil count (ANC) major than/equal to 1500/microL
• Platelets major than/equal to 100,000/microL
• Hemoglobin major than/equal to 9.0 g/dL
• Serum creatinine less than/equal to 1.5 x ULN
12. Signed and dated informed consent document indicating that the patient
(or legally acceptable representative) has been informed of all the pertinent
aspects of the trial prior to enrollment.
13. Willingness and abil
Exclusion criteria:
1. Histology of inflammatory carcinoma.
2. Prior treatment with omore than/ equal to2 regimens of cytotoxic therapy in the advanced disease
setting.
3. Prior treatment on a SU011248 clinical trial.
4. Prior treatment with any tyrosine kinase inhibitors, VEGF inhibitors, or other
angiogenic inhibitors.
5. Major surgery, radiation therapy, or systemic therapy within 3 weeks of study
randomization except palliative radiotherapy to non-target metastatic lesions.
6. Prior high-dose chemotherapy requiring hematopoietic stem cell rescue.
7. Prior radiation therapy to >25% of the bone marrow.
8. Current treatment on another clinical trial.
9. Uncontrolled brain metastases, spinal cord compression, carcinomatous
meningitis, or leptomeningeal disease. Patients should have completed surgery
or radiation therapy for existing brain metastases, should not have documented
increase in size over the previous 3 months prior to first dose of treatment on
study and should be asymptomatic.
10. Diagnosis of any second malignancy within the last 3 years, except for
adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ
of the cervix.
11. Any of the following within the 12 months prior to starting study treatment:
myocardial infarction, severe/unstable angina, coronary/peripheral artery
bypass graft, congestive heart failure, cerebrovascular accident including
transient ischemic attack, or pulmonary embolus.
12. Ongoing cardiac dysrhythmias of NCI CTCAE grade major than/equal to 2, atrial
fibrillation of any grade, or QTc interval >470 msec
13. Hypertension that cannot be controlled by medications (>150/100 mmHg
despite optimal medical therapy).
14. Current treatment with therapeutic doses of Coumadin (low dose Coumadin up
to 2 mg PO daily for deep vein thrombosis prophylaxis is allowed).
15. Known human immunodeficiency virus infection.
16. Pregnancy or breastfeeding. All female patients with reproductive potential
must have a negative pregnancy test (serum or urine) prior to randomization.
17. Other severe acute or chronic medical or psychiatric condition, or laboratory
abnormality that would impart, in the judgment of the investigator, excess risk
associated with study participation or study drug administration, or which, in the
judgment of the investigator, would make the patient inappropriate for entry
into this study.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Histologically or cytologically proven diagnosis of breast cancer with evidence of 1) unresectable, locally recurrent, or 2) metastatic disease. Documentation of estrogen and progestin receptor (ER/PR) negative status and HER2/neu receptor negative status (ie, FISH negative or immunohistochemistry 0 or +1).
MedDRA version: 7.1 Level: LLY Classification code 10055113

Intervention(s)

Product Code: SU011248 L-Malate Salt
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: sunitinib malate
CAS Number: 341031-54-7
Current Sponsor code: SU011248
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 12,5-

Product Code: SU011248 L-Malate Salt
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: sunitinib malate
CAS Number: 341031-54-7
Current Sponsor code: SU011248
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Product Code: SU011248 L-Malate Salt
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: sunitinib malate
CAS Number: 341031-54-7
Current Sponsor code: SU011248
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Primary Outcome(s)

Primary end point(s): Progression-free survival (PFS)

Main Objective: To compare the progression-free survival for SU011248 versus standard-of-care therapy in patients with previously treated, triple receptor negative (ER/PR and HER2/neu), locally recurrent or metastatic breast cancer .

Secondary Objective: • To assess the safety of SU011248 versus standard-of-care in this patient population
• To assess measures of duration of tumor control and overall survival
• To assess patient reported outcomes
• To determine SU011248 and SU012662 (active metabolite of SU011248) trough plasma concentrations (Ctrough) and to potentially explore the relationship between Ctrough, efficacy, and safety

Secondary ID(s)

2005-003774-15-GB

A6181077