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

• Register: EUCTR
• Last refreshed on: 18 April 2012
• Main ID: EUCTR2005-003774-15-DE
• Date of registration: 21/12/2005
• Prospective Registration: Yes
• Primary sponsor: Pfizer Pharma GmbH
• 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
• 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
• Date of first enrolment: 19/01/2006
• 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: yes Other trial design description: Crossover at the time of disease progression from the control arm to SU011248 will be offered If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

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 or Cish (where approved) negative
or immunohistochemistry 0 or +1).
3. Prior treatment with an anthracycline and a taxane in the neoadjuvant, 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, documented
disease progression after discontinuing treatment.
Patients entering the study on the basis of this criterion may have also
previously received neoadjuvant or 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 3 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 t
Exclusion criteria:
1. Histology of inflammatory carcinoma.
2. Prior treatment with omore than/ equal to 2 regimens of cytotoxic therapy in the advanced disease
setting.
3. Prior treatment on a SU011248 clinical trial.
4. Exclusion criterion 4 deleted by Protocol Amendment 1.
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)

Trade Name: SUTENT
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
Other descriptive name: PHA-290940AD
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 12,5-

Trade Name: SUTENT
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
Other descriptive name: PHA-290940AD
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Trade Name: SUTENT
Product Code: SU011248 L-Malate Salt
Pharmaceutical Form: Capsule, hard
CAS Number: 341031-54-7
Current Sponsor code: SU011248
Other descriptive name: PHA-290940AD
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Product Name: Capecitabine
Pharmaceutical Form: Tablet
INN or Proposed INN: Capecitabine
CAS Number: 154361-50-9
Current Sponsor code: Capecitabine
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: range
Concentration number: 1000-1250

Product Name: Vinorelbine
Pharmaceutical Form: Intravenous infusion
INN or Proposed INN: Vinorelbine
CAS Number: 71486-22-1
Current Sponsor code: Vinorelbine
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: range
Concentration number: 25-30

Product Name: Docetaxel
Pharmaceutical Form: Intravenous infusion
INN or Proposed INN: Docetaxel
CAS Number: 114977-28-5
Current Sponsor code: Docetaxel
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: range
Concentration number: 75-100

Product Name: Paclitaxel
Pharmaceutical Form: Intravenous infusion
INN or Proposed INN: Paclitaxel
CAS Number: 33069-62-4
Current Sponsor code: Paclitaxel
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: range
Concentration number: 80-200

Product Name: Gemcitabine
Pharmaceutical Form: Intravenou

Primary Outcome(s)

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 .

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

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
• To explore the relationship between specific biomarkers and cancer- and treatment-related outcomes

Secondary ID(s)

2005-003774-15-GB

A6181077