The main goal of neoadjuvant therapy should be a pathological complete response (pCR), because pCR more accurately predicts improved patient outcome and prolonged survival. In the present study, pathological response will be evaluated by The Miller…
ID
Source
Brief title
Condition
- Breast neoplasms malignant and unspecified (incl nipple)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- To evaluate clinical and pathological response to neoadjuvant chemotherapy
- To evaluate the value of dynamic contrast-enhanced breast MRI in monitoring
and predicting response to neoadjuvant chemotherapy.
- To evaluate the value of circulating tumour cells in monitoring and
predicting reponse to neoadjuvant chemotherapy.
- To define gene expression profiles that can predict treatment response or
failure by microarray analysis.
Secondary outcome
- To determine disease-free and overall survival.
- To evaluate the use of radioactive labeled (125-I) seed as to localize tumour
prior to chemotherapy to enable - after surgical excision (conservation
therapy or mastectomy) pathological evaluation of tumour residue after
chemotherapy
Background summary
Docetaxel-based neoadjuvant chemotherapy is an effective alternative to surgery
followed by adjuvant chemotherapy in both early and locally advanced breast
cancer. Findings from randomized studies suggests that the sequential
administration of docetaxel and anthracycline-based therapy may provide
improved outcome versus the outcome with concomitant administration. Recently,
the Dutch multidisciplinary guidelines for treatment of early breast cancer
were updated and antracycline-based therapy consisting of FEC was defined as
standard treament. Therefore, in the present study, eligible patients will be
treated with sequential 4 cycles of docetaxel after 4 cycles of neoadjuvant
FEC. In line with the data of Van Pelt and Buzdar, patients with HER-2 positive
disease will be treated with 8 cycles of docetaxel in combination with
trastuzumab. Trastuzumab and docetaxel will be administered in a 3-weekly
schedule based on the data of Leyland-Jones.
Study objective
The main goal of neoadjuvant therapy should be a pathological complete response
(pCR), because pCR more accurately predicts improved patient outcome and
prolonged survival. In the present study, pathological response will be
evaluated by The Miller and Payne and RECIST classification system (see
appendix I). In addition clinical response to treatment will be evaluated by
dynamic contrast-enhanced MRI of the effected breast. Breast MRI images will be
correlated to the pathological information to determine whether this technique
is able to accurately predict tumour response to neoadjuvant chemotherapy.
Moreover, repetitive breast MRI images obtained before, during and after
chemotherapy offers the ability to determine the optimal duration of
preoperative therapy and to delineate the necessity to change the regimen in
chemotherapy-resistant tumours
Study design
Multi centre, phase II - non randomised - study.
Study burden and risks
Neo adjuvant chemotherapy is indicated based on criteria also used for adjuvant
chemotherapy. Advantages could be: - monitoring clinical respons and
possibility of adjustment of treatment, - possibility of breast saving
procedure after (nearly) complete respons of large breast tumours. This
treatment is also made possible after placement of 125-I seed.
Michelangelolaan 2
5623 EJ Eindhoven
Nederland
Michelangelolaan 2
5623 EJ Eindhoven
Nederland
Listed location countries
Age
Inclusion criteria
•Women presenting with locally advanced stage IIB-III breast cancer pT2 > 3 cm, and/or clinically proven N+ disease. Exclusion cT4. (TNM classification 2002).
•No prior surgery other than biopsy and no prior chemotherapy or radiation therapy.
•Age > 18 years and age < 60 years.
•Karnofsky Performance status index > 80%
•Estrogen and/or progesterone receptor analysis performed on the primary tumour. Results must be known by the end of chemoptherapy in order to decide whether hormonal therapy is indicated.
•Her2/neu receptor analysis performed on the primary tumour.
•Adequate bone marrow (within 14 days prior to registration):WBC > 3.0 x 109/l, neutrophils > 1.5 x 109/l, platelets > 100 x 109/l, hemoglobin > 7 mmol/l.
•Adequate liver function (within 21 days prior to registration):bilirubin < 1 x upper limit of normal (UNL) range, ALAT and/or ASAT < 2.5 x UNL, Alkaline Phosphatase < 5 x UNL.
•Adequate renal function (within 21 days prior to registration):Creatinine < 120 µmol/L; if limit values reached, the calculated creatinine clearance should be > 60 mL/min.
•No sign of metastatic disease on X-thorax, liver ultrasound or nuclear bone scan.
•Cardiac LVEF evaluation by ECHO or MUGA (within normal limits).
•Patients must be accessible for treatment and follow-up.
•Negative pregnancy test (urine or serum) within 7 days prior to registration for all women of childbearing potential.
•Having signed written informed consent according to the local Ethics Committee requirements.
Exclusion criteria
•Prior systemic anticancer therapy for any cancer (immunotherapy, hormonaltherapy, genetherapy, chemotherapy).
•Prior anthracycline-based or taxoid-containing therapy (paclitaxel, docetaxel) for any malignancy.
•Prior radiation therapy for breast cancer.
•Patients with advanced pulmonary disease.
•Peripheral neuropathy > grade 2 whatever the cause.
•Clinical evidence of CNS disease.
•Patients with a history of another malignancy (except basal cell skin carcinoma and carcinoma-in-situ of the uterine cervix) within 5 years of study entry.
•Pregnant or lactating women, or potentially fertile women not using adequate contraception.
•Clinically T4
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2006-001206-89-NL |
| CCMO | NL11339.060.06 |