A PHASE 2 EFFICACY AND SAFETY STUDY OF SU011248 IN COMBINATION WITH TRASTUZUMAB AS TREATMENT FOR METASTATIC DISEASE IN PATIENTS WITH BREAST CANCER

• Conditions: locally recurrent or metastatic BC; MedDRA version: 7.1Level: LLYClassification code 10055113

• Registration Number: EUCTR2005-003773-25-BE
• Lead Sponsor: PFIZER s.a.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-01-16
• Last Update Posted: 7 October 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 128

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. Measurable disease as per Response Evaluation Criteria in Solid Tumors
(RECIST). Measurable lesions that have been previously radiated will not be
considered target lesions unless an increase in size is observed following
completion of radiation therapy.
3. HER2 positive disease (3+ by immunohistochemistry [IHC] or FISH-positive)
4. Candidate for treatment with trastuzumab. Prior treatment with trastuzumab
and/or lapatinib in the neoadjuvant, adjuvant or metastatic disease setting is
permitted. Treatment with hormone therapy in the adjuvant and/or advanced
disease setting is permitted
5. Inclusion criterion 5 deleted by Protocol Amendment 2.
6. Patients receiving bisphosphonate therapy for metastatic bone disease must
have initiated therapy at least 3 weeks prior to the first dose of study drug.
7. Female or male, 18 years of age or older.
8. ECOG performance status 0 or 1
9. Resolution of all acute toxic effects of prior therapy or surgical procedures to
grade less thaN/equal to 1 (except alopecia).
10. Adequate organ function as defined by the following criteria:
• Serum aspartate transaminase (AST) and serum alanine transaminase
(ALT) = 2.5 x upper limit of normal (ULN), or AST and ALT less = 5 x ULN if liver
function abnormalities are due to underlying malignancy
• Total serum bilirubin =1.5 x ULN
• Serum albumin =3.0 g/dL
• Absolute neutrophil count (ANC) =1500/microL
• Platelets =100,000/microL
• Hemoglobin =9.0 g/dL
•Serum creatinine =to 1.5 x ULN
11. 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.
12. Willingness and ability to comply with scheduled visits, treatment plans,
laboratory tests, and other study procedures.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Exclusion criterion 1 deleted by Protocol Amendment 2.
2. Prior treatment with >1 regimen of cytotoxic therapy in the advanced disease
setting therapy is permitted. A regimen is defined as treatment until progression,
regardless of therapies included in that regimen prior to progression.
3. Exclusion criterion 3 deleted by Protocol Amendment 2.
4. Prior exposure to trastuzumab if the patient had developed severe
hypersensitivity reactions.
5. Exclusion criterion 5 deleted by Protocol Amendment 2.
6. Prior treatment on a SU011248 clinical trial.
7. Major surgery, radiation therapy, or systemic therapy within 3 weeks of first dose
of study treatment except palliative radiotherapy to non-target metastatic lesions.
8. Prior high-dose chemotherapy requiring hematopoietic stem cell rescue.
9. Prior radiation therapy to >25% of the bone marrow.
10. Current treatment on another clinical trial.
11. Exclusion criterion 11 deleted by Protocol Amendment 2.
12. 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 of lesions over the previous 3 months prior to the first dose of
study drug and should be asymptomatic.
13. 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.
14. 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.
15. Ongoing cardiac dysrhythmias of NCI CTCAE grade =2, atrial fibrillation of any
grade, or QTc interval >450 msec for males or >470 msec for females.
16. Hypertension that cannot be controlled by medications (>150/100 mmHg
despite optimal medical therapy).
17. Current treatment with therapeutic doses of Coumadin (low dose Coumadin up
to 2 mg PO daily for deep vein thrombosis prophylaxis is allowed).
18. Known human immunodeficiency virus infection.
19. Pregnancy or breastfeeding. All female patients with reproductive potential must
have a negative pregnancy test (serum or urine) prior to first dose of study
treatment.
20. 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To estimate the objective response rate (ORR) for the combination of trastuzumab and SU011248 in locally recurrent or metastatic BC ;Secondary Objective: • To evaluate the safety and tolerability of SU011248 administered in combination <br> with trastuzumab in this patient population<br>• To assess measures of duration of tumor control and survival<br>• To assess patient reported outcomes<br>• To determine SU011248 and SU012662 (active metabolite of SU011248) plasma <br> trough concentrations (Ctrough ) in combination with trastuzumab and to <br> potentially explore the relationship between Ctrough and efficacy, and safety<br>;Primary end point(s): Objective response rate (ORR)