breast cancer
Conditions
Interventions
Sponsors
Oslo University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Cohort I: Patients with large (radiologic measureable tumor > 2.0 cm) HER2 negative mammary carcinomas in the following categories are eligible for inclusion into the study: • T2 tumors with: o Ki67 labeling index = 20% or o ER positive and Progesterone receptor negative status or o grade 3 tumors • T3-T4 tumors with Ki67 = 15%. The patients should not have received previous treatment for the current disease and should be without signs of metastatic disease as determined by liver ultrasound or CT scan and bone scintigraphy or MRI. Cohort II: Patients with evaluable metastatic disease from breast carcinoma according to the RECIST criteria, AND elegible for biopsy of the metastatic tumor for diagnosis and research purposes before, during and after therapy. 1. Written informed consent obtained prior to any study-specific procedure 2. Female or male age ?18 years 3. Able to comply with the protocol 4. Histologically or cytologically confirmed, HER2-negative, men or women with breast adenocarcinoma 5. WHO performance status = 2 6. Adequate hematological function Absolute neutrophil count (ANC) =1.0 x 109/L AND Platelet count =100 x 109/L AND Hemoglobin = 10 g/dL (may be transfused to maintain or exceed this level) 7. Adequate liver function Total bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: 1. Previous chemotherapy treatment for localized breast cancer less than 24 months before inclusion into study (cohort I) or metastatic breast cancer treated with taxane (cohort II). 2. Other earlier or concomitant carcinoma less than five years prior to the breast cancer diagnosis, except for BCC, in situ cervix cancer or breast cancer 3. Clinically significant (i.e. active) cardiovascular disease for example CVA (=6 months before enrolment), myocardial infarction (=6 months before enrolment), unstable angina, congestive heart failure (CHF) NYHA Class =II, serious cardiac arrhythmia requiring medication during the study, which might interfere with regularity of the study treatment, or not controlled by medication 4. Treatment with any other investigational agent, or participation in another clinical intervention trial within 21 days prior to enrolment 5. Evidence of any other disease, neurological or metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment-related complications.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to determine the molecular (DNA, RNA, protein and metabolic) changes in the tumors with reference to the obtained response in the different treatment arms. The molecular and metabolic characteristics and changes in the tumors will be evaluated by analyses of tumor samples taken before, under (if possible) and after the scheduled treatment period using: •DNA analyses, including whole genome SNP and methylation analyses in addition to RNA microarray analyses •Protein tissue arrays, protein arrays and protein kinase activity •High resolution MR magnetic angle spinning (HR-MAS) analyses The responses will be evaluated by available imaging technologies. If possible, functional imaging technologies will also be used for response evaluation: •Magnetic resonance imaging (diffusion weighted and contrast enhanced MRI) and MR spectroscopy (MRS) •PET based imaging modalities ;Secondary Objective: •Analysis of the characteristics of circulating tumor-DNA in plasma samples, circulating tumor cells (CTC) in peripheral blood, at the time points for the tumor sampling with comparison to the tumor analysis and according to the different treatment arms. •Course of fatigue during different treatment regimens and predictors of chronic fatigue after treatment. ;Primary end point(s): •Alteration in the DNA profiles, SNP analysis and presence of different tumor cell clones as verified by the difference in DNA analysis in the tumors of the patients in the different treatment groups related to the particular clinical responses with emphasis on responses (complete response (pCR) or partial responses) in the breast and in the lymph nodes or objective measured responses (OR) for metastatic patients.;Timepoint(s) of evaluation of this end point: After 24 weeks of treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Molecular changes in the protein kinase expression, mRNA/miRNA expression and protein expression and metabolome in the different treatment groups. • Treatment induced changes and characteristics in circulating tumor DNA and circulating tumor cells in peripheral blood compared to tumor response. • Response rate in the treatment groups. • Difference in levels of fatigue between treatment arms. • Host-related, tumor-related and treatment-related factors predicting chronic fatigue. ;Timepoint(s) of evaluation of this end point: After 24 weeks of treatment. | — |
Countries
Norway
Contacts
Public ContactOlav Engebråten
Oslo University Hospital
Outcome results
None listed