Sequential vs Upfront Intensified Neoadjuvant Chemotherapy in Patients With Large Resectable or Locally Advanced Breast Cancer. (INTENS)

Radboud University Medical Center

Status and phase: Completed; Phase 3

Conditions: Breast Cancer

Treatments: Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Docetaxel

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00314977

IKO 2005-01 / BOOG 2007-02

Details and patient eligibility

About

2 different treatment schedules may be used for neoadjuvant chemotherapy in breast cancer using adriamycin, cyclophosphamide and taxotere. The most optimal sequence- concurrent or sequential- is however unclear. The aim of the study is to compare the efficacy and tolerability of neoadjuvant chemotherapy with AC followed by T(adriamycin, cyclophosphamide, taxotere) versus TAC ( with upfront T) in patient with large resectable or locally advanced breast cancer.

Enrollment: 200 estimated patients

Sex: Female

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Women presenting with large resectable or locally advanced breast cancer (T2 ≥3 cm, T3, or T4, and/or LN positive)
• Measurable disease (breast and/or lymph nodes)
• No prior surgery other than biopsy and no prior chemotherapy or radiation therapy
• Age ≥18 years and age ≤70 years
• Karnofsky Performance score ≥70%
• Estrogen and/or progesterone receptor analysis performed on the primary tumour in the biopsy material
• In case the tumor is ER/PgR ³ 50% positive, (neo)adjuvant hormonal therapy in stead of chemotherapy should be considered (e.g. in TEAM II study)
• Her2/neu receptor analysis performed on the primary tumour in the biopsy material
• Adequate bone marrow function (within 14 days prior to registration): WBC ≥3.0 x 109/l, neutrophils ≥1.5 x 109/l, platelets ≥100 x 109/l
• Adequate liver function (within 4 weeks prior to start treatment): bilirubin ≤1.5 x upper limit of normal (UNL) range, ALAT and/or ASAT ≤2.5 x UNL, Alkaline Phosphatase ≤5 x UNL
• Adequate renal function (within 4 weeks prior to start treatment): the calculated creatinine clearance should be ≥50 mL/min
• Patients must be accessible for treatment and follow-up
• Written informed consent according to the local Ethics Committee requirements

Exclusion criteria

• Patients with advanced pulmonary disease of any cause (oxygen dependent)- Peripheral neuropathy > grade 2 whatever the cause
• Serious other diseases as recent myocardial infarction, clinical signs of cardiac failure or clinically significant arrythmias
• Evidence of distant metastases (M1)
• Patients with a history of breast cancer
• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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200 participants in 2 patient groups

A

Experimental group

Description:

Cycles 1-4 q 3 weeks: doxorubicin plus cyclophosphamide Cycles 5-8 q 3 weeks: docetaxel

Treatment:

Drug: Docetaxel

Drug: Doxorubicin

Drug: Cyclophosphamide

B

Experimental group

Description:

Cycles 1-6 q 3 weeks: doxorubicin, cyclophosphamide and docetaxel

Treatment:

Drug: Docetaxel

Drug: Doxorubicin

Drug: Cyclophosphamide