Clinical trial NCT00129376: Doxorubicin and Cyclophosphamide (AC) Followed by Weekly Docetaxel as Neoadjuvant Treatment of Breast Cancer Patients
Official title: Multicenter Phase II Trial of Doxorubicin and Cyclophosphamide (AC) Followed by Weekly Docetaxel (T) as Neoadjuvant Treatment for Operable Stage II and IIIA Breast Cancer Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: Stage II and IIIA breast Cancer.
Neoadjuvant chemotherapy.
Weekly docetaxel.
Lead sponsor: Spanish Breast Cancer Research Group
Sponsor class: OTHER
Collaborators: name: Sanofi
First posted: 2005-08-11
Enrollment: 63
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Treatment consists of 4 AC cycles followed by 2 weekly docetaxel cycles (12 infusions).

The pathological complete response rate obtained in previous studies is around 12%. The expected pathological complete response rate in this study is 25%. With an alpha error of 0.05 and a beta error of 0.2, and following Simon´s 2 phase test, 19 patients are needed initially. With 2 pathological complete responses, patient recruitment will continue until approximately 61 patients are recruited. Twelve pathological complete responses are needed to confirm the study hypothesis.

Detailed description: Patients received doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2), both in a short intravenous infusion, every three weeks for four cycles (days 1, 22, 43 and 64). Three weeks later, docetaxel (36 mg/m2) was administered as a 30-min intravenous infusion, weekly for six weeks (days 85, 92, 99, 106, 113 and 120) followed by a 2-week resting period (8-week cycle). After that, patients received a second docetaxel cycle (infusions on days 141, 148, 155, 162, 169 and 176). Adjuvant chemotherapy and radiotherapy were delivered according to the protocol of each participating center. Hormonal treatment was started after the last chemotherapy infusion in all patients with positive estrogen and/or progesterone receptor tumors and was continued for five years.

Semiquantitative determination of three molecular markers was carried out by immunocytochemical methods. Tissue samples were taken prior to initiation of chemotherapy from the core of the primary tumors. Specimens were sent to a central laboratory for analysis of Topo II, survivin and p27.

Eligibility criteria: Inclusion Criteria:

* Written informed consent.
* Patients with breast cancer stages II and IIIA, with histological diagnoses as per true-cut or open biopsy.
* Negative extension study, including bilateral mammography, thoracic x-ray, computed tomography (CT)-scan or abdominal echography and bone scintigraphy.
* Analysis of hormone receptor status in primary tumour. It is highly recommended to obtain a tumour tissue sample before start of treatment, and after definitive surgery. These samples will be analysed centrally by Spanish Breast Cancer Research Group (GEICAM).
* Age \>= 18 and \<= 70 years old.
* Performance status as per Karnofsky index \>= 80.
* Minimum life expectancy of 6 months.
* Electrocardiogram (EKG) 12 weeks before registration to the study. If abnormalities are suspected, cardiac function must be assessed by left ventricular ejection fraction (LVEF).
* Haematology: neutrophils \>= 2.0 x10\^9/l; platelets \>= 100 x10\^9/l; hemoglobin \>=10 g/dl.
* Hepatic function: total bilirubin \<= 1 x upper normal limit (UNL); Aspartate aminotransferase (AST) (SGOT) and and Alanine aminotransferase (ALT) (SGPT) \<= 2.5 x UNL; alkaline phosphatase \<= 5 x UNL.
* Renal function: creatinine \<= 1.5 x UNL; creatinine clearance \>= 60 ml/min.
* Patients able to comply with study requirements.
* Negative pregnancy test.
* Adequate contraceptive method during the study and up to 3 months after definitive surgery.

Exclusion Criteria:

* Previous systemic therapy for breast cancer treatment.
* Previous treatments with anthracyclines or taxanes for any malignancy.
* Previous radiotherapy for breast cancer.
* Bilateral invasive breast cancer.
* Pregnant or lactating women.
* Previous motor or sensorial neurotoxicity grade \>=2.
* Other serious pathologies: congestive heart failure or angina pectoris; history of myocardial infarction in the previous year; uncontrolled hypertension (HT) or high risk arrhythmias.
* History of neurological or psychiatric impairment, precluding patients from providing free informed consent.
* Active infection.
* Active peptic ulcer; unstable diabetes mellitus.
* History of previous or current malignancies other than breast cancer, except for basal skin carcinoma, cervical in situ carcinoma, other tumour diagnosed and treated more than 10 years before, ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS).
* Chronic treatment with corticoids unless the treatment started \> 6 months before registration to the study, and low doses are administered.
* Substitutive hormonal therapy. This treatment must be interrupted before inclusion in the study.
* Concomitant treatment with other investigational products or administration in the 30 previous days.
* Males.

Primary outcomes:
measure: Pathological Complete Response (pCR) Rate
timeFrame: Up to 29 weeks
Secondary outcomes:
measure: Clinical Response Rate (CRR)
timeFrame: Up to 29 weeks
measure: Number of Participants With Over-expression of Topo II (>10% Cells With Nuclear Staining)
timeFrame: Up to 29 weeks
measure: Number of Participants With Over-expression of Survivin (>1% Cells With Nuclear Staining)
timeFrame: Up to 29 weeks
measure: Number of Participants With Over-expression of p27 (>75% Cells With Nuclear Staining)
timeFrame: Up to 29 weeks
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Hospital Universitario Germans Trias i Pujol
state: Barcelona
city: Sabadell
country: Spain
facility: Corporació Sanitaria Parc Taulí
state: Barcelona
city: Alcira
country: Spain
facility: Hospital de la Ribera
state: Valencia
city: A Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Madrid
country: Spain
facility: Fundación Jiménez Díaz
Study officials:
affiliation: Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz
name: Study Director
role: STUDY_DIRECTOR
affiliation: Hospital Universitario Marqués de Valdecilla
name: Study Director
role: STUDY_DIRECTOR
References: