A RANDOMIZED, DOUBLE-BLIND, PHASE 2 STUDY OF SU011248 IN COMBINATION WITH TRASTUZUMAB AS FIRST-LINE TREATMENT FOR METASTATIC DISEASE IN PATIENTS WITH BREAST CANCER
- Conditions
- 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.MedDRA version: 7.1Level: LLYClassification code 10055113
- Registration Number
- EUCTR2005-003773-25-ES
- Lead Sponsor
- PFIZER S.A
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 160
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 Tumor (RECIST)
Mesurable 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 (3+by immunochemisty [IHC] or FISH-positive)
4. Candidate for treatment with single-agent trastuzumab.
5. Not a candidate for or do not want to receive treatment that includes
chemotherapy agents.
6. Patients receiving bisphosphonate therapy for metastatic bone disease must
have initiated therapy at least 4 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. The definitions of minimum adequacy for organ function required prior to study
entry are as follows.
• 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
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
1. Histology of inflammatory carcinoma.
2. Prior exposure to trastuzumab and/or chemotherapy in the adjuvant setting if
relapse occurred during treatment or if disease free interval was less than 12
months from the last dose of the adjuvant therapy.
3. Prior exposure to trastuzumab if the patient had developed severe ypersensitivity
reactions.
4. Prior treatment with chemotherapy and/or trastuzumab in the advanced disease
setting. Treatment with hormone therapy in the adjuvant and/or advanced
disease setting is permitted.
5. Prior treatment on a SU011248 clinical trial.
6. Prior treatment with any tyrosine kinase inhibitors, VEGF inhibitors, or other
angiogenic inhibitors.
7. Major surgery, radiation therapy, or systemic therapy within 3 weeks of study
randomization 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. Known metastases in more than /equal to 50 % of the liver, presence in more
than 3 organs, or symptomatic pulmonary metastases.
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 major tha/equal to 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 randomization.
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 or placebo in locally recurrent or metastatic BC.;Primary end point(s): Objective response rate (ORR);Secondary Objective: • To evaluate the safety and tolerability of SU011248 or placebo administered in <br> combination 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) trough <br>plasma concentrations (Ctrough ) in combination with trastuzumab and to potentially explore the relationship between Ctrough and efficacy, and safety <br>
- Secondary Outcome Measures
Name Time Method