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: 25 November 2019
• Main ID: EUCTR2005-003774-15-GB
• Date of registration: 06/10/2005
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc., 235 East 42nd Street, New York, 10017, United States
• 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: 09/08/2007
• 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: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

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

Key inclusion & exclusion criteria

Inclusion criteria:
Patients must meet all of the following inclusion criteria to be eligible for enrollment into the trial:
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 with chemotherapy, OR
• Receipt of chemotherapy in the first- or second-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 or non-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. (Enrollment of patients having bone-only disease is at the discretion of Principal Investigators and Institutional Review Boards/Ethics Committees at participating institutions. Patients having bone-only disease will be required to undergo an additional bone scan at week 6 of the study).
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. Deleted in Amendment #2 (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, 1 or 2.
10. Resolution of all acute toxic effects of prior therapy or surgical procedures to grade =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) =2.5 x Upper Limit of Normal (ULN), or AST and ALT =5 x ULN if liver function abnormalities are due to underlying malignancy
• Total serum bilirubin =1.5 x ULN. (Patients with Gilbert’s disease may not be required to meet this criterion)• Serum albumin =2.5 g/dL

Exclusion criteria:
Patients presenting with any of the following will not be included in the trial:
1. Deleted in Amendment #2 (histology of inflammatory carcinoma).
2. Prior treatment with =3 regimens of cytotoxic therapy in the advanced disease setting.
3. Prior treatment on a SU011248 clinical trial.
4. Deleted in Amendment #1 (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. Deleted in Amendment #2 (prior high-dose chemotherapy requiring hematopoietic stem cell rescue).
7. Deleted in Amendment #2 (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 contralateral breast cancer also with triple negative receptor status, adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix.
11. Any of the following within the 6 months prior to starting study treatment: myocardial infarction, severe/unstable angina, congestive heart failure, cerebrovascular accident including transient ischemic attack, or pulmonary embolus.
12. 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.
13. Hypertension that cannot be controlled by medications (>150/100 mmHg despite optimal medical therapy).
14. Current treatment with therapeutic doses of coumarin or oral anti-vitamin K agents such as warfarin and phenprocoumon derivatives (use of low doses for deep vein thrombosis prophylaxis is allowed). Low molecular weight heparin is allowed at any dose level.
15. Known human immunodeficiency virus infection.
16. Female who is pregnant or nursing; female of child-bearing potential who is unwilling or unable to use adequate contraception to prevent pregnancy during the trial and for 3 months after the last dose of study treatment. All female patients with reproductive potential must have a negative pregnancy test (serum or urine) prior to randomization. For patients enrolled in the United Kingdom, adequate contraception is defined as double barrier contraception.
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: 9.1 Level: LLT Classification code 10027475 Term: Metastatic breast cancer

Intervention(s)

Trade Name: Sutent
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Sunitinib Malate
CAS Number: 341031-54-7
Current Sponsor code: SU-011248
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 12.5-

Trade Name: Sutent
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Sunitinib Malate
CAS Number: 341031-54-7
Current Sponsor code: SU-011248
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Trade Name: Sutent
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Sunitinib Malate
CAS Number: 341031-54-7
Current Sponsor code: SU-011248
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

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

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

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

Secondary ID(s)

A6181077

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 06/02/2015
• Date Completed: 15/06/2011
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2005-003774-15/results