Studieoverzicht - 2010-01 NEO-ZOTAC

Randomization:
Arm A: 6x TAC with Zoledronic acid
Arm B: 6x TAC without Zoledronic acid

Primary objective:

• To determine the value of adding zoledronic acid to neoadjuvant chemotherapy with TAC in patients with large resectable or locally advanced HER2-negative breast cancer.

Secondary objectives:

• To evaluate the clinical response, correlated to the pathological responses of both treatment arms.
• To evaluate the disease free survival and overall survival.
• To evaluate the safety and tolerability of adding zoledronic acid to neoadjuvant chemotherapy.
• To evaluate heterogeneity of the ER/PR and HER2 measurement of the core biopsy and the operation specimen.

Primary endpoint:

• Pathologic complete response (pCR) rate to neoadjuvant chemotherapy with or without zoledronic acid at surgery.
   

Secondary endpoints:

• Clinical response (partial and complete according to RECIST v1.1, evaluated with MRI) of neoadjuvant therapy correlated to pathological response.
• Disease free survival and overall survival after 3 and 5 years follow up, correlated to pCR.
• Tolerability (grade 3 / 4 CTC toxicities) of both regimens.
• Pathology: ER/PR and HER2 heterogeneity in core biopsy vs. Operation specimen.

Inclusion:

• Women presenting with large resectable or locally advanced breast cancer (T2,T3,T4, every N, M0)
• Measurable disease (breast and/or ymph nodes)
• Histological proven HER2-negative breast cancer in the core biopsy material.
• Age ≥18 years
• WHO 0-2
• Adequate bone marrow function (within 14 days prior to registration): WBC ≥3.0 x 10E9/l, neutrophils ≥1.5 x 10E9/l, platelets ≥100 x 10E9/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: the calculated creatinine clearance should be ≥50 ml/min

Exclusion:

• Evidence of distant metastases (M1)
• History of breast cancer
• Prior breast surgery other than biopsy
• Prior chemotherapy or radiation therapy
• Previous malignancy within 5 years, with exception of a history of a previous basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix.
• Prior bisphosphonate usage.
• Peripheral neuropathy > grade 2, whatever the cause
• Serious other diseases as recent myocardial infarction, clinical signs of cardiac failure or clinically significant arrhythmias.
• Current active dental problems including dental abscess or infection of the jawbone (maxilla or mandible), or a current or prior diagnosis of osteonecrosis of the jaw requiring maxillofacial
  surgery.Known hypersensitivity reaction to any of the components of the treatment
• Pregnancy or lactating

BOOG 2010-01 NEO-ZOTAC protocol synopsis V2