None listed
Conditions
Brief summary
The ANZ 0502 (Neo Gem) clinical trial is conducted by the Australian New Zealand Breast Cancer Trials Group (ANZ BCTG) in a number of hospitals in Australia and New Zealand. The trial is for women with newly diagnosed large operable breast cancer or locally advanced breast cancer - which often involves the lymph nodes under the armpit (axillary nodes). Larger operable and locally advanced breast cancers are associated with a poorer prognosis and higher risk of micometastatic disease. Standard treatment for this type of breast cancer usually includes chemotherapy to try to reduce the size of the cancer, followed by surgery and radiation therapy to treat any remaining cancer in the breast. Whilst this treatment is successful in removing the cancer from the breast in the majority of patients, there is a significant risk of the cancer recurring. The treatment in this trial will involve a course of standard chemotherapy (epirubicin and cyclophosphamide) followed by a course of two newer chemotherapy drugs for breast cancer (docetaxel and gemcitabine), followed by surgery. The delivery of chemotherapy prior to surgery offers the potential to substantially reduce the size of primary breast tumours and allow for breast-conserving surgery or surgical resection of previously inoperable tumours. It is hoped to also reduce the risk of recurrence of the breast cancer. The trial includes provision for patients with breast cancer tumours which overexpress HER2, by adding trastuzumab (Herceptin) to the docetaxel and gemcitabine (DGH) treatment cycles in order to maximise the efficacy of all three agents.
Interventions
All patients will receive 4 cycles of epirubicin (90mg/m2, IV, Day 1) and cyclophosphamide (600mg/m2 IV, Day 1) followed by 4 cycles of Taxotere™ (docetaxel, 75mg/m2, IV, Day 1) and Gemzar® (gemcitabine, 1000mg/m2 IV, Days 1 & 8), with the addition of Herceptin® (trastuzumab) if the tumour is HER2 positive (trastuzumab: Cycle 1: 4mg/kg IV day 1, 2mg/kg IV day 8 & 15; Cycles 2-4, 2mg/kg IV day 1, 8 & 15; 6mg/kg IV day 22 of Cycle 4). Trastuzumab will be given for a total duration of one year (
All patients will receive 4 cycles of epirubicin (90mg/m2, IV, Day 1) and cyclophosphamide (600mg/m2 IV, Day 1) followed by 4 cycles of Taxotere™ (docetaxel, 75mg/m2, IV, Day 1) and Gemzar® (gemcitabine, 1000mg/m2 IV, Days 1 & 8), with the addition of Herceptin® (trastuzumab) if the tumour is HER2 positive (trastuzumab: Cycle 1: 4mg/kg IV day 1, 2mg/kg IV day 8 & 15; Cycles 2-4, 2mg/kg IV day 1, 8 & 15; 6mg/kg IV day 22 of Cycle 4). Trastuzumab will be given for a total duration of one year (13 x 3 weekly cycles). Larger operable and locally advanced tumours are associated with a poorer prognosis and a high risk of micrometastatic disease and require aggressive multimodality therapy. Anthracycline-based chemotherapy remains the core of most pre or postoperative chemotherapy regimens for early or locally advanced breast cancer unless contraindicated. Given promising data, including the established benefit of docetaxel in the adjuvant setting and the use of gemcitabine in metastatic breast cancer, suggesting non-cross resistance and synergy with the taxanes, a phase II study consisting of 4 cycles of epirubicin and cyclophosphamide followed by 4 cycles of docetaxel (day 1) and gemcitabine (day 1 & 8) each cycle delivered every three weeks is proposed. For patients with HER2 overexpressing breast cancer, the addition of trastuzumab to the docetaxel and gemcitabine treatment cycles aims to maximize synergy seen between all three agents and minimize cardiac toxicity. These regimens aim to maximize the pathologic complete response rate (pCR) rate which may translate into a survival benefit in the long term. Breast cancer tissue will also be obtained to correlate clinical and pathologic response with changes in molecular parameters.
Sponsors
ANZ Breast Cancer Trials Group Ltd.
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Female patients with a confirmed new diagnosis of unilateral, operable primary breast cancer, (clinically and/or on ultrasound), T2 (=3cm only), T3-4, N0-1, M0, diagnosed by core biopsy. The disease must be considered operable at first presentation. HER2 expression must be determined using either immunohistochemistry or FISH.• Patients with HER2 negative breast cancer must have a measured left ventricular ejection fraction of = 50% with MUGA or echocardiogram. Patients with HER2 positive breast cancer must have a measured left ventricular ejection fraction of = 55% with MUGA or echocardiogram.• No prior chemotherapy or hormonal therapy for breast cancer or other invasive cancer.• Adequate bone marrow, hepatic and renal function• ECOG performance status of 0, 1 or 2.• Women of child-bearing potential must have a negative pregnancy test and agree to use an accepted and effective method of non-hormonal contraception (barrier method of birth control; abstinence).• An ability to understand and the willingness to sign a written informed consent document.• Patients must be accessible for follow-up.• Patients must be informed of and agree to data and tissue material transfer and handling, in accordance with national data protection guidelines.
Exclusion criteria
Prior chemotherapy or hormonal therapy for breast cancer or other invasive cancer.• Patients with inoperable, or inflammatory or metastatic breast cancer.• History of an active malignancy other than in situ carcinoma of the cervix, or non-melanomatous skin cancers in the last five years prior to registration to the study.• Patients may not be receiving any other investigational agents.• Congestive heart failure (New York Heart Association (NYHA) Class III-IV) or history of congestive failure, unstable angina pectoris, myocardial infarction in the last 6 months, poorly controlled hypertension (systolic >180 mmHg or diastolic > 100 mmHg), clinically significant valvular disease, or high risk uncontrolled arrhythmias. • History of significant neurologic or psychiatric disorders including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent.• Patients with dyspnoea at rest due to malignant or other disease or who require supportive oxygen therapy. • Patients who are pregnant or lactating at the time of registration to the trial. • Any active uncontrolled infection.• Any other medical condition which the investigator’s opinion makes the subject unsuitable for study participation.• Patients with a history of hypersensitivity reaction to products containing Polysorbate 80 (Tween).
Outcome results
None listed